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Clinical Trial Results:
A Phase 2, Multicenter, Open-Label, Active Comparator-Controlled, Extension Trial to Evaluate the Long-Term Safety and Efficacy of CP-690,550 in Renal Allograft Recipients

Summary
EudraCT number	2008-002345-23
Trial protocol	DE ES PT BE NL IT CZ
Global end of trial date	09 Jun 2015

Results information
Results version number	v1(current)
This version publication date	27 Aug 2016
First version publication date	27 Aug 2016
Other versions

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

A3921050

ISRCTN number

US NCT number

NCT00658359

WHO universal trial number (UTN)

Sponsor organisation name

Pfizer, Inc.

Sponsor organisation address

Corporate Office: 235 East 42nd Street, New York, United States, NY 10017

Public contact

Pfizer ClinicalTrials.gov Call Center, Pfizer, 00-1 8007181021, ClinicalTrials.gov_Inquiries@pfizer.com

Scientific contact

Pfizer ClinicalTrials.gov Call Center, Pfizer, 00-1 8007181021, ClinicalTrials.gov_Inquiries@pfizer.com

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

03 Feb 2016

Is this the analysis of the primary completion data?

Yes

Primary completion date

10 Mar 2015

Global end of trial reached?

Yes

Global end of trial date

09 Jun 2015

Was the trial ended prematurely?

Main objective of the trial

Participants who had completed 12 months treatment with tofacitinib or cyclosporine (CsA) in previous parent study (A3921030) continued study drugs for an additional 60 months in this extension study (except in Portugal where study treatment was continued through 3 years posttransplant, after which subjects completed a follow up visit 2 months after the last dose). The main objective of this trial was to evaluate the long-term safety, tolerability and efficacy of tofacitinib including the incidence of biopsy proven acute rejection (BPAR) (as interpreted by the central pathologist) and treated clinical acute rejection (episodes that were diagnosed clinically and received antirejection treatment).

Protection of trial subjects

Throughout this study, subjects were monitored for clinical evidence of acute rejection, clinically significant infections, malignancies, and graft survival. In addition to the protocol biopsy scheduled at Month 36, allograft biopsy was considered when clinically indicated to assess the etiology of deteriorating renal function. A Data Monitoring Committee (DMC) was established for the study and acted in an advisory capacity to the sponsor’s study team. The DMC included internal (sponsor) members as well as members external to the sponsor who had transplant expertise. The DMC was responsible for ongoing monitoring of the efficacy and safety of subjects in the study according to the Charter. Any recommendations made by the DMC to alter the conduct of the study were forwarded to the sponsor for final decision. The sponsor forwarded such decisions to regulatory authorities, as appropriate.

Background therapy

Participants also received oral mycophenolate mofetil (MMF) 1 to 2 gram tablet daily throughout this extension study (or up to 3 mg daily for Black participants). Prednisone 5mg daily (or equivalent) was also maintained through at least 12 months posttransplant (parent study).

Evidence for comparator

Cyclosporine (CsA) was administered for up to 60 months as CsA microemulsion (Neoral® brand in the United States) orally twice daily (BID) in 2 equal doses approximately 12 hours apart. The dosage was adjusted to achieve a 12 hour trough whole blood level of approximately 75 to 200 nanograms per milliliter (ng/mL). The selection of the doses for this extension study was based on the review of data from the completed Study A3921030.

Actual start date of recruitment

18 Aug 2008

Long term follow-up planned

Yes

Long term follow-up rationale

Safety, Efficacy

Long term follow-up duration

60 Months

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Australia: 19

Country: Number of subjects enrolled

Belgium: 9

Country: Number of subjects enrolled

Brazil: 22

Country: Number of subjects enrolled

Canada: 1

Country: Number of subjects enrolled

Czech Republic: 2

Country: Number of subjects enrolled

France: 6

Country: Number of subjects enrolled

Germany: 4

Country: Number of subjects enrolled

Italy: 7

Country: Number of subjects enrolled

Korea, Republic of: 12

Country: Number of subjects enrolled

Netherlands: 5

Country: Number of subjects enrolled

Norway: 3

Country: Number of subjects enrolled

Poland: 4

Country: Number of subjects enrolled

Portugal: 7

Country: Number of subjects enrolled

Spain: 5

Country: Number of subjects enrolled

United States: 72

Worldwide total number of subjects

178

EEA total number of subjects

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

167

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

Participants were recruited and studied between 18 August 2008 and 18 February 2015. Those with 6-month time-weighted concentrations at 2-hours postdose (TWC2) above the median (Amendment 3), negative/unknown Epstein-Barr virus (EBV) at transplant, cytomegalovirus disease or lymphocyte-depleting agents posttransplant (Amendment 4) were discontinued

Screening details

Number of subjects started

178

Number of subjects completed

178

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Non-randomised - controlled

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Cyclosporine (CsA)

Arm description

CsA was administered for up to 60 months as CsA microemulsion (Neoral® brand in the United States) orally twice daily (BID) in 2 equal doses approximately 12 hours apart. The dosage was adjusted to achieve a 12 hour trough whole blood level of approximately 75 to 200 nanograms per milliliter (ng/mL). Participants also received oral mycophenolate mofetil (MMF) 1 to 2 gram tablet daily throughout this extension study (or up to 3 mg daily for Black participants). Prednisone 5mg daily (or equivalent) was also maintained through at least 12 months posttransplant (parent study).

Arm type

Active comparator

Investigational medicinal product name

cyclosporine

Investigational medicinal product code

Other name

Pharmaceutical forms

Oral emulsion

Routes of administration

Oral use

Dosage and administration details

Orally BID in 2 equal doses approximately 12 hours apart. The dosage was adjusted to achieve a 12 hour trough whole blood level of approximately 75 to 200 ng/mL

Tofacitinib Less Intensive (LI)

Arm description

Tofacitinib was administered for up to 60 months. During the parent study (A3921030), participants received 15 milligram (mg) tablet orally BID for Months 1 to 3 posttransplant then 10 mg tablet orally BID from Month 4. On entry to this extension study (Month 12), the dose was continued and tapered to 5 mg BID as early as Month 12 and by Month 18 posttransplant. Total tofacitinib LI treatment was up to 72 months posttransplant (12 months parent study and 60 months extension). Participants also received oral MMF 1 to 2 gram tablet daily throughout this extension study. Prednisone 5mg daily (or equivalent) was also maintained through at least 12 months posttransplant (parent study).

Arm type

Experimental

Investigational medicinal product name

tofacitinib

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Oral 10mg BID on study entry reducing to 5mg BID by Month 18

Tofacitinib More Intensive (MI)

Arm description

Tofacitinib was administered for up to 60 months. During the parent study (A3921030), participants received 15 mg tablet orally BID for Months 1 to 6 posttransplant then 10 mg tablet orally BID from Month 7. On entry to this extension study (Month 12), the dose was continued and tapered to 5 mg BID as early as Month 12 and by Month 18 posttransplant. Total tofacitinib MI treatment was up to 72 months posttransplant (12 months parent study and 60 months extension). Participants also received oral MMF 1 to 2 gram tablet daily throughout this extension study. Prednisone 5mg daily (or equivalent) was also maintained through at least 12 months posttransplant (parent study).

Arm type

Experimental

Investigational medicinal product name

tofacitinib

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Oral 10mg BID on study entry reducing to 5mg BID by Month 18

Number of subjects in period 1	Cyclosporine (CsA)	Tofacitinib Less Intensive (LI)	Tofacitinib More Intensive (MI)
Started	64	60	54
Completed	36	15	8
Not completed	28	45	46
Adverse event, serious fatal	3	1	2
Consent withdrawn by subject	7	4	2
Adverse event, non-fatal	13	6	9
Other reasons including protocol Amendment 3 and 4	2	31	29
Lost to follow-up	2	2	4
Protocol deviation	1	-	-
Lack of efficacy	-	1	-

Baseline characteristics

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Reporting group title

Cyclosporine (CsA)

Reporting group description

Reporting group title

Tofacitinib Less Intensive (LI)

Reporting group description

Reporting group title

Tofacitinib More Intensive (MI)

Reporting group description

Reporting group values	Cyclosporine (CsA)	Tofacitinib Less Intensive (LI)	Tofacitinib More Intensive (MI)	Total
Number of subjects	64	60	54	178
Age categorical
Units: Subjects
Adults (18-64 years)	60	57	50	167
From 65-84 years	4	3	4	11
Age Continuous \|
Age refers to the beginning of the parent study (A3921030)
Units: years
arithmetic mean (standard deviation)	46.4 ( 12.7 )	45.7 ( 12.6 )	48.5 ( 10.9 )	-
Gender, Male/Female
Units: Participants
Female	20	19	14	53
Male	44	41	40	125
Race
Units: Subjects
White	46	45	34	125
Black	8	7	7	22
Asian	5	6	9	20
Other	5	2	4	11
Weight
Weight refers to the beginning of the parent study (A3921030)
Units: kilogram [kg]
arithmetic mean (standard deviation)	75.9 ( 15.5 )	74.9 ( 18.3 )	79.5 ( 21.7 )	-
Body Mass Index
Body mass index refers to the beginning of the parent study (A3921030)
Units: kg/meter squared [kg/m^2]
arithmetic mean (standard deviation)	26.2 ( 4.6 )	25.6 ( 5 )	26.9 ( 5.4 )	-
Height
Height refers to the beginning of the parent study (A3921030)
Units: centimeter [cm]
arithmetic mean (standard deviation)	169.8 ( 9.3 )	170.5 ( 9.9 )	171.1 ( 11.3 )	-

Subject analysis set title

Full Analysis Set (FAS)

Subject analysis set type

Full analysis

Subject analysis set description

The FAS included all subjects who were enrolled in the study and received at least 1 dose of study drug in Study A3921050.

Subject analysis set title

Safety Analysis Set

Subject analysis set type

Safety analysis

Subject analysis set description

The Safety Analysis Set was defined as those subjects who received at least 1 dose of study drug in Study A3921050 (note that the FAS and the Safety Analysis Set were the same).

Subject analysis sets values	Full Analysis Set (FAS)	Safety Analysis Set
Number of subjects	178	178
Age categorical
Units: Subjects
Adults (18-64 years)	167	167
From 65-84 years	11	11
Age Continuous \|
Age refers to the beginning of the parent study (A3921030)
Units: years
arithmetic mean (standard deviation)	46.8 ( 12.2 )	46.8 ( 12.2 )
Gender, Male/Female
Units: Participants
Female	53	53
Male	125	125
Race
Units: Subjects
White	125	125
Black	22	22
Asian	20	20
Other	11	11
Weight
Weight refers to the beginning of the parent study (A3921030)
Units: kilogram [kg]
arithmetic mean (standard deviation)	76.7 ( 18.5 )	76.7 ( 18.5 )
Body Mass Index
Body mass index refers to the beginning of the parent study (A3921030)
Units: kg/meter squared [kg/m^2]
arithmetic mean (standard deviation)	26.2 ( 5 )	26.2 ( 5 )
Height
Height refers to the beginning of the parent study (A3921030)
Units: centimeter [cm]
arithmetic mean (standard deviation)	170.4 ( 10.1 )	170.4 ( 10.1 )

End points

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Reporting group title

Cyclosporine (CsA)

Reporting group description

Reporting group title

Tofacitinib Less Intensive (LI)

Reporting group description

Reporting group title

Tofacitinib More Intensive (MI)

Reporting group description

Subject analysis set title

Full Analysis Set (FAS)

Subject analysis set type

Full analysis

Subject analysis set description

The FAS included all subjects who were enrolled in the study and received at least 1 dose of study drug in Study A3921050.

Subject analysis set title

Safety Analysis Set

Subject analysis set type

Safety analysis

Subject analysis set description

The Safety Analysis Set was defined as those subjects who received at least 1 dose of study drug in Study A3921050 (note that the FAS and the Safety Analysis Set were the same).

Primary: Kaplan-Meier Analysis of Percentage of Participants with Clinically Significant Infection (CSI) by Visit

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End point title

Kaplan-Meier Analysis of Percentage of Participants with Clinically Significant Infection (CSI) by Visit

End point description

CSI was defined as the presence of documented infection confirmed by culture, biopsy, genomic, or serologic findings post-randomization and requiring hospitalization or parenteral anti-infective treatment, or otherwise deemed significant by the investigator. The 'Number' and 'Confidence Interval 60%' columns represent cumulative proportions and 60% confidence intervals (CIs) as estimated from the fitted Kaplan-Meier curves for each treatment at scheduled visits.

End point type

Primary

End point timeframe

Months 12, 15, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72

End point values	Cyclosporine (CsA)	Tofacitinib Less Intensive (LI)	Tofacitinib More Intensive (MI)
Number of subjects analysed	64	60	54
Units: Percentage of Participants
number (confidence interval 60%)
Month 12 (n=61, 55, 52)	4.69 (2.46 to 6.91)	8.33 (5.33 to 11.34)	3.7 (1.54 to 5.87)
Month 15 (n=59,54,44)	7.81 (4.99 to 10.64)	10 (6.74 to 13.26)	18.52 (14.07 to 22.97)
Month 18 (n=57,52,41)	9.4 (6.33 to 12.48)	13.33 (9.64 to 17.03)	20.46 (15.83 to 25.09)
Month 24 (n=54,48,34)	11.02 (7.71 to 14.33)	18.33 (14.13 to 22.54)	24.49 (19.51 to 29.47)
Month 30 (n=49,34,23)	12.8 (9.23 to 16.36)	25.42 (20.64 to 30.21)	29.46 (24 to 34.92)
Month 36 (n=46,28,12)	14.62 (10.81 to 18.42)	27.83 (22.79 to 32.87)	34.89 (28.2 to 41.57)
Month 42 (n=40,28,11)	14.62 (10.81 to 18.42)	27.83 (22.79 to 32.87)	34.89 (28.2 to 41.57)
Month 48 (n=37,28,11)	16.81 (12.68 to 20.93)	27.83 (22.79 to 32.87)	34.89 (28.2 to 41.57)
Month 54 (n=36,25,10)	19.05 (14.62 to 23.48)	33.08 (27.52 to 38.64)	34.89 (28.2 to 41.57)
Month 60 (n=34,21,10)	19.05 (14.62 to 23.48)	36.13 (30.26 to 41.99)	34.89 (28.2 to 41.57)
Month 66 (n=29,19,8)	19.05 (14.62 to 23.48)	36.13 (30.26 to 41.99)	34.89 (28.2 to 41.57)
Month 72 (n=24,15,7)	21.94 (17.05 to 26.84)	40.12 (33.73 to 46.51)	43.03 (34.35 to 51.7)

Percentage of Participants with CSI by Visit

Statistical analysis description

Month 15

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[1]

P-value

= 0.6694

Method

Wald Test

Parameter type

Mean difference (final values)

Point estimate

2.19

Confidence interval

level

60%

sides

2-sided

lower limit

-2.12

upper limit

6.5

Variability estimate

Standard error of the mean

Dispersion value

5.12

Notes
[1] - Point estimates, lower and upper confidence limits represent percentages. The mean difference and standard error of the mean is the percentage difference and standard error of the percentage difference.

Percentage of Participants with CSI by Visit

Statistical analysis description

Month 15

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[2]

P-value

= 0.0873

Method

Wald Test

Parameter type

Mean difference (final values)

Point estimate

10.71

Confidence interval

level

60%

sides

2-sided

lower limit

5.44

upper limit

15.98

Variability estimate

Standard error of the mean

Dispersion value

6.26

Notes
[2] - Point estimates, lower and upper confidence limits represent percentages. The mean difference and standard error of the mean is the percentage difference and standard error of the percentage difference.

Percentage of Participants with CSI by Visit

Statistical analysis description

Month 18

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[3]

P-value

= 0.4912

Method

Wald Test

Parameter type

Mean difference (final values)

Point estimate

3.93

Confidence interval

level

60%

sides

2-sided

lower limit

-0.87

upper limit

8.74

Variability estimate

Standard error of the mean

Dispersion value

5.71

Notes
[3] - Point estimates, lower and upper confidence limits represent percentages. The mean difference and standard error of the mean is the percentage difference and standard error of the percentage difference.

Percentage of Participants with CSI by Visit

Statistical analysis description

Month 18

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[4]

P-value

= 0.0942

Method

Wald Test

Parameter type

Mean difference (final values)

Point estimate

11.06

Confidence interval

level

60%

sides

2-sided

lower limit

5.5

upper limit

16.62

Variability estimate

Standard error of the mean

Dispersion value

6.61

Notes
[4] - Point estimates, lower and upper confidence limits represent percentages. The mean difference and standard error of the mean is the percentage difference and standard error of the percentage difference.

Percentage of Participants with CSI by Visit

Statistical analysis description

Month 24

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[5]

P-value

= 0.2499

Method

Wald Test

Parameter type

Mean difference (final values)

Point estimate

7.31

Confidence interval

level

60%

sides

2-sided

lower limit

1.96

upper limit

12.66

Variability estimate

Standard error of the mean

Dispersion value

6.36

Notes
[5] - Point estimates, lower and upper confidence limits represent percentages. The mean difference and standard error of the mean is the percentage difference and standard error of the percentage difference.

Percentage of Participants with CSI by Visit

Statistical analysis description

Month 24

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[6]

P-value

= 0.058

Method

Wald Test

Parameter type

Mean difference (final values)

Point estimate

13.47

Confidence interval

level

60%

sides

2-sided

lower limit

7.49

upper limit

19.45

Variability estimate

Standard error of the mean

Dispersion value

7.1

Notes
[6] - Point estimates, lower and upper confidence limits represent percentages. The mean difference and standard error of the mean is the percentage difference and standard error of the percentage difference.

Percentage of Participants with CSI by Visit

Statistical analysis description

Month 30

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[7]

P-value

= 0.075

Method

Wald Test

Parameter type

Mean difference (final values)

Point estimate

12.62

Confidence interval

level

60%

sides

2-sided

lower limit

6.66

upper limit

18.59

Variability estimate

Standard error of the mean

Dispersion value

7.09

Notes
[7] - Point estimates, lower and upper confidence limits represent percentages. The mean difference and standard error of the mean is the percentage difference and standard error of the percentage difference.

Percentage of Participants with CSI by Visit

Statistical analysis description

Month 30

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[8]

P-value

= 0.0316

Method

Wald Test

Parameter type

Mean difference (final values)

Point estimate

16.66

Confidence interval

level

60%

sides

2-sided

lower limit

10.14

upper limit

23.19

Variability estimate

Standard error of the mean

Dispersion value

7.75

Notes
[8] - Point estimates, lower and upper confidence limits represent percentages. The mean difference and standard error of the mean is the percentage difference and standard error of the percentage difference.

Percentage of Participants with CSI by Visit

Statistical analysis description

Month 36

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[9]

P-value

= 0.0783

Method

Wald Test

Parameter type

Mean difference (final values)

Point estimate

13.21

Confidence interval

level

60%

sides

2-sided

lower limit

6.9

upper limit

19.53

Variability estimate

Standard error of the mean

Dispersion value

7.5

Notes
[9] - Point estimates, lower and upper confidence limits represent percentages. The mean difference and standard error of the mean is the percentage difference and standard error of the percentage difference.

Percentage of Participants with CSI by Visit

Statistical analysis description

Month 36

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[10]

P-value

= 0.0266

Method

Wald Test

Parameter type

Mean difference (final values)

Point estimate

20.27

Confidence interval

level

60%

sides

2-sided

lower limit

12.58

upper limit

27.96

Variability estimate

Standard error of the mean

Dispersion value

9.14

Notes
[10] - Point estimates, lower and upper confidence limits represent percentages. The mean difference and standard error of the mean is the percentage difference and standard error of the percentage difference.

Percentage of Participants with CSI by Visit

Statistical analysis description

Month 42

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[11]

P-value

= 0.0783

Method

Wald Test

Parameter type

Mean difference (final values)

Point estimate

13.21

Confidence interval

level

60%

sides

2-sided

lower limit

6.9

upper limit

19.53

Variability estimate

Standard error of the mean

Dispersion value

7.5

Notes
[11] - Point estimates, lower and upper confidence limits represent percentages. The mean difference and standard error of the mean is the percentage difference and standard error of the percentage difference.

Percentage of Participants with CSI by Visit

Statistical analysis description

Month 42

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[12]

P-value

= 0.0266

Method

Wald Test

Parameter type

Mean difference (final values)

Point estimate

20.27

Confidence interval

level

60%

sides

2-sided

lower limit

12.58

upper limit

27.96

Variability estimate

Standard error of the mean

Dispersion value

9.14

Notes
[12] - Point estimates, lower and upper confidence limits represent percentages. The mean difference and standard error of the mean is the percentage difference and standard error of the percentage difference.

Percentage of Participants with CSI by Visit

Statistical analysis description

Month 48

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[13]

P-value

= 0.1545

Method

Wald Test

Parameter type

Mean difference (final values)

Point estimate

11.02

Confidence interval

level

60%

sides

2-sided

lower limit

4.51

upper limit

17.54

Variability estimate

Standard error of the mean

Dispersion value

7.74

Notes
[13] - Point estimates, lower and upper confidence limits represent percentages. The mean difference and standard error of the mean is the percentage difference and standard error of the percentage difference.

Percentage of Participants with CSI by Visit

Statistical analysis description

Month 48

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[14]

P-value

= 0.0528

Method

Wald Test

Parameter type

Mean difference (final values)

Point estimate

18.08

Confidence interval

level

60%

sides

2-sided

lower limit

10.22

upper limit

25.94

Variability estimate

Standard error of the mean

Dispersion value

9.34

Notes
[14] - Point estimates, lower and upper confidence limits represent percentages. The mean difference and standard error of the mean is the percentage difference and standard error of the percentage difference.

Percentage of Participants with CSI by Visit

Statistical analysis description

Month 54

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[15]

P-value

= 0.0968

Method

Wald Test

Parameter type

Mean difference (final values)

Point estimate

14.03

Confidence interval

level

60%

sides

2-sided

lower limit

6.92

upper limit

21.14

Variability estimate

Standard error of the mean

Dispersion value

8.45

Notes
[15] - Point estimates, lower and upper confidence limits represent percentages. The mean difference and standard error of the mean is the percentage difference and standard error of the percentage difference.

Percentage of Participants with CSI by Visit

Statistical analysis description

Month 54

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[16]

P-value

= 0.0966

Method

Wald Test

Parameter type

Mean difference (final values)

Point estimate

15.83

Confidence interval

level

60%

sides

2-sided

lower limit

7.81

upper limit

23.85

Variability estimate

Standard error of the mean

Dispersion value

9.53

Notes
[16] - Point estimates, lower and upper confidence limits represent percentages. The mean difference and standard error of the mean is the percentage difference and standard error of the percentage difference.

Percentage of Participants with CSI by Visit

Statistical analysis description

Month 60

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[17]

P-value

= 0.0507

Method

Wald Test

Parameter type

Mean difference (final values)

Point estimate

17.07

Confidence interval

level

60%

sides

2-sided

lower limit

9.72

upper limit

24.42

Variability estimate

Standard error of the mean

Dispersion value

8.74

Notes
[17] - Point estimates, lower and upper confidence limits represent percentages. The mean difference and standard error of the mean is the percentage difference and standard error of the percentage difference.

Percentage of Participants with CSI by Visit

Statistical analysis description

Month 60

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[18]

P-value

= 0.0966

Method

Wald Test

Parameter type

Mean difference (final values)

Point estimate

15.83

Confidence interval

level

60%

sides

2-sided

lower limit

7.81

upper limit

23.85

Variability estimate

Standard error of the mean

Dispersion value

9.53

Notes
[18] - Point estimates, lower and upper confidence limits represent percentages. The mean difference and standard error of the mean is the percentage difference and standard error of the percentage difference.

Percentage of Participants with CSI by Visit

Statistical analysis description

Month 66

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[19]

P-value

= 0.0507

Method

Wald Test

Parameter type

Mean difference (final values)

Point estimate

17.07

Confidence interval

level

60%

sides

2-sided

lower limit

9.72

upper limit

24.42

Variability estimate

Standard error of the mean

Dispersion value

8.74

Notes
[19] - Point estimates, lower and upper confidence limits represent percentages. The mean difference and standard error of the mean is the percentage difference and standard error of the percentage difference.

Percentage of Participants with CSI by Visit

Statistical analysis description

Month 66

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[20]

P-value

= 0.0966

Method

Wald Test

Parameter type

Mean difference (final values)

Point estimate

15.83

Confidence interval

level

60%

sides

2-sided

lower limit

7.81

upper limit

23.85

Variability estimate

Standard error of the mean

Dispersion value

9.53

Notes
[20] - Point estimates, lower and upper confidence limits represent percentages. The mean difference and standard error of the mean is the percentage difference and standard error of the percentage difference.

Percentage of Participants with CSI by Visit

Statistical analysis description

Month 72

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[21]

P-value

= 0.0574

Method

Wald Test

Parameter type

Mean difference (final values)

Point estimate

18.17

Confidence interval

level

60%

sides

2-sided

lower limit

10.12

upper limit

26.22

Variability estimate

Standard error of the mean

Dispersion value

9.56

Notes
[21] - Point estimates, lower and upper confidence limits represent percentages. The mean difference and standard error of the mean is the percentage difference and standard error of the percentage difference.

Percentage of Participants with CSI by Visit

Statistical analysis description

Month 72

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[22]

P-value

= 0.0749

Method

Wald Test

Parameter type

Mean difference (final values)

Point estimate

21.08

Confidence interval

level

60%

sides

2-sided

lower limit

11.12

upper limit

31.04

Variability estimate

Standard error of the mean

Dispersion value

11.84

Notes
[22] - Point estimates, lower and upper confidence limits represent percentages. The mean difference and standard error of the mean is the percentage difference and standard error of the percentage difference.

Percentage of Participants with CSI by Visit

Statistical analysis description

Month 12

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[23]

P-value

= 0.4116

Method

Wald Test

Parameter type

Mean difference (final values)

Point estimate

3.65

Confidence interval

level

60%

sides

2-sided

lower limit

-0.09

upper limit

7.38

Variability estimate

Standard error of the mean

Dispersion value

4.44

Notes
[23] - Point estimates, lower and upper confidence limits represent percentages. The mean difference and standard error of the mean is the percentage difference and standard error of the percentage difference.

Percentage of Participants with CSI by Visit

Statistical analysis description

Month 12

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[24]

P-value

= 0.7895

Method

Wald Test

Parameter type

Mean difference (final values)

Point estimate

-0.98

Confidence interval

level

60%

sides

2-sided

lower limit

-4.09

upper limit

2.12

Variability estimate

Standard error of the mean

Dispersion value

3.69

Notes
[24] - Point estimates, lower and upper confidence limits represent percentages. The mean difference and standard error of the mean is the percentage difference and standard error of the percentage difference.

Primary: Percentage of Participants with Malignancies

Top of page

End point title

Percentage of Participants with Malignancies

End point description

All treatment-emergent malignancies in Study A3921050 were included as collected on the Malignancy Case Report Form page.

End point type

Primary

End point timeframe

Months 12 through 72.

End point values	Cyclosporine (CsA)	Tofacitinib Less Intensive (LI)	Tofacitinib More Intensive (MI)
Number of subjects analysed	64	60	54
Units: Percentage of Participants
number (not applicable)	10.9	13.3	14.8

Percentage of Participants with Malignancies

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[25]

P-value

= 0.683

Method

Chi-squared

Parameter type

Mean difference (final values)

Point estimate

2.4

Confidence interval

level

95%

sides

2-sided

lower limit

-9.1

upper limit

13.9

Variability estimate

Standard error of the mean

Dispersion value

5.9

Notes
[25] - 'Mean difference' and 'standard error of the mean' refers to 'percentage difference' and 'standard error of the percentage difference'

Percentage of Participants with Malignancies

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[26]

P-value

= 0.529

Method

Chi-squared

Parameter type

Mean difference (final values)

Point estimate

3.9

Confidence interval

level

95%

sides

2-sided

lower limit

-8.3

upper limit

16.1

Variability estimate

Standard error of the mean

Dispersion value

6.2

Notes
[26] - 'Mean difference' and 'standard error of the mean' refers to 'percentage difference' and 'standard error of the percentage difference'

Primary: Least Squares Means of Measured Glomerular Filtration Rate (GFR) (Iohexol Serum Clearance in Milliliters per Minute [mL/min])

Top of page

End point title

Least Squares Means of Measured Glomerular Filtration Rate (GFR) (Iohexol Serum Clearance in Milliliters per Minute [mL/min])

End point description

GFR: an index of kidney function. GFR described the flow rate of filtered fluid through the kidney. GFR was calculated using iohexol serum clearance. For determination of iohexol serum clearance, iohexol was administered as an intravenous (IV) bolus over 5 minutes immediately after morning dosing of Tofacitinib or CsA on day of GFR evaluation. Blood samples for iohexol (3 millilitres [mL] each to provide a minimum of 1 mL serum) were collected into appropriately labeled tubes containing no additives at 120, 180, 240, and 300 minutes after the end of the iohexol IV bolus. A normal GFR is greater than (>) 90 mL/min, although children and older people usually have a lower GFR. Lower values indicated poor kidney function. A GFR less than (<) 15 mL/min indicated kidney failure.

End point type

Primary

End point timeframe

Month 36

End point values	Cyclosporine (CsA)	Tofacitinib Less Intensive (LI)	Tofacitinib More Intensive (MI)
Number of subjects analysed	39	30	13
Units: mL/min
least squares mean (standard error)	67.63 ( 3.38 )	76.86 ( 3.74 )	75.86 ( 5.35 )

Treatment Comparisons of Measured GFR

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[27]

P-value

= 0.0699

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

9.23

Confidence interval

level

60%

sides

2-sided

lower limit

4.97

upper limit

13.49

Variability estimate

Standard error of the mean

Dispersion value

5.04

Notes
[27] - 'Standard error of the mean' refers to 'standard error of the mean difference'

Treatment Comparisons of Measured GFR

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[28]

P-value

= 0.1958

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

8.23

Confidence interval

level

60%

sides

2-sided

lower limit

2.89

upper limit

13.58

Variability estimate

Standard error of the mean

Dispersion value

6.32

Notes
[28] - 'Standard error of the mean' refers to 'standard error of the mean difference'

Primary: Percentage of Participants with Progression of Chronic Allograft Lesions (CAL) at Month 36

Top of page

End point title

Percentage of Participants with Progression of Chronic Allograft Lesions (CAL) at Month 36

End point description

Progression of CAL was defined as an increase in the Banff chronicity score (Banff-CS) in biopsy from the implantation (baseline) biopsy in a given participant. Banff-CS was the sum of the Banff scores for the 4 chronic basic lesions (allograft glomerulopathy [cg] + interstitial fibrosis [ci] + tubular atrophy [ct] + vascular intimal thickening [cv]). The Banff-CS ranged from 0-12, higher score indicated greater lesions and Month 36 Banff-CS greater than the implantation biopsy score indicated progression of lesions.

End point type

Primary

End point timeframe

Month 36

End point values	Cyclosporine (CsA)	Tofacitinib Less Intensive (LI)	Tofacitinib More Intensive (MI)
Number of subjects analysed	24	18	8
Units: Percentage of Participants
number (not applicable)	87.5	77.78	87.5

Percentage of Participants with Progression of CAL

Statistical analysis description

Month 36

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[29]

P-value

= 0.438

Method

Chi-squared

Parameter type

Difference in percentage

Point estimate

-9.72

Confidence interval

level

sides

2-sided

lower limit

-100

upper limit

100

Variability estimate

Standard deviation

Dispersion value

Notes
[29] - Analysis uses Tofacitinib LI minus CsA. No confidence interval or dispersion value was calculated. The confidence interval and dispersion values provided are artificial numbers NOT from the study.

Percentage of Participants with Progressive CAL

Statistical analysis description

Month 36

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[30]

P-value

> 0.999

Method

Chi-squared

Parameter type

Difference in percentage

Point estimate

Confidence interval

level

sides

2-sided

lower limit

-100

upper limit

100

Variability estimate

Standard deviation

Dispersion value

Notes
[30] - Analysis uses Tofacitinib MI minus CsA. No confidence interval or dispersion value was calculated. The confidence interval and dispersion values provided are artificial numbers NOT from the study

Primary: Kaplan-Meier Analysis of Percentage of Participants with first Biopsy Proven Acute Rejection (BPAR) by Visit

Top of page

End point title

Kaplan-Meier Analysis of Percentage of Participants with first Biopsy Proven Acute Rejection (BPAR) by Visit

End point description

BPAR was category acute rejection as interpreted by the central blinded pathologist according to the Banff 97 working classification. The 'Number' and 'Confidence Interval 60%' columns represent cumulative proportions and 60% CIs as estimated from the fitted Kaplan-Meier curves for each treatment at scheduled visits..

End point type

Primary

End point timeframe

Months 12, 15, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72

End point values	Cyclosporine (CsA)	Tofacitinib Less Intensive (LI)	Tofacitinib More Intensive (MI)
Number of subjects analysed	64	60	54
Units: Percentage of Participants
number (confidence interval 60%)
Month 12 (n=60,54,51)	6.25 (3.7 to 8.8)	10 (6.74 to 13.26)	5.56 (2.93 to 8.18)
Month 15 (n=59,54,50)	7.81 (4.99 to 10.64)	10 (6.74 to 13.26)	7.41 (4.41 to 10.41)
Month 18 (n=57,54,48)	9.4 (6.33 to 12.48)	10 (6.74 to 13.26)	7.41 (4.41 to 10.41)
Month 24 (n=55,53,42)	9.4 (6.33 to 12.48)	10 (6.74 to 13.26)	7.41 (4.41 to 10.41)
Month 30 (n=51,37,28)	9.4 (6.33 to 12.48)	10 (6.74 to 13.26)	7.41 (4.41 to 10.41)
Month 36 (n=48,28,14)	11.18 (7.82 to 14.54)	10 (6.74 to 13.26)	7.41 (4.41 to 10.41)
Month 42 (n=40,28,13)	13.34 (9.61 to 17.08)	10 (6.74 to 13.26)	7.41 (4.41 to 10.41)
Month 48 (n=38,28,13)	13.34 (9.61 to 17.08)	10 (6.74 to 13.26)	7.41 (4.41 to 10.41)
Month 54 (n=38,27,12)	13.34 (9.61 to 17.08)	10 (6.74 to 13.26)	7.41 (4.41 to 10.41)
Month 60 (n=36,23,11)	13.34 (9.61 to 17.08)	10 (6.74 to 13.26)	7.41 (4.41 to 10.41)
Month 66 (n=31,20,10)	13.34 (9.61 to 17.08)	10 (6.74 to 13.26)	7.41 (4.41 to 10.41)
Month 72 (n=28,18,10)	13.34 (9.61 to 17.08)	10 (6.74 to 13.26)	7.41 (4.41 to 10.41)

Percentage of Participants with First BPAR

Statistical analysis description

Month 15

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[31]

P-value

= 0.6694

Method

Wald Test

Parameter type

Mean difference (final values)

Point estimate

2.19

Confidence interval

level

60%

sides

2-sided

lower limit

-2.12

upper limit

6.5

Variability estimate

Standard error of the mean

Dispersion value

5.12

Notes
[31] - Point estimates, lower and upper confidence limits represent percentages. The mean difference and standard error of the mean is the percentage difference and standard error of the percentage difference.

Percentage of Participants with First BPAR

Statistical analysis description

Month 15

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[32]

P-value

= 0.934

Method

Wald Test

Parameter type

Mean difference (final values)

Point estimate

-0.41

Confidence interval

level

60%

sides

2-sided

lower limit

-4.52

upper limit

3.71

Variability estimate

Standard error of the mean

Dispersion value

4.89

Notes
[32] - Point estimates, lower and upper confidence limits represent percentages. The mean difference and standard error of the mean is the percentage difference and standard error of the percentage difference.

Percentage of Participants with First BPAR

Statistical analysis description

Month 18

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[33]

P-value

= 0.9106

Method

Wald Test

Parameter type

Mean difference (final values)

Point estimate

0.6

Confidence interval

level

60%

sides

2-sided

lower limit

-3.88

upper limit

5.08

Variability estimate

Standard error of the mean

Dispersion value

5.32

Notes
[33] - Point estimates, lower and upper confidence limits represent percentages. The mean difference and standard error of the mean is the percentage difference and standard error of the percentage difference.

Percentage of Participants with First BPAR

Statistical analysis description

Month 18

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[34]

P-value

= 0.696

Method

Wald Test

Parameter type

Mean difference (final values)

Point estimate

-1.99

Confidence interval

level

60%

sides

2-sided

lower limit

-6.29

upper limit

2.3

Variability estimate

Standard error of the mean

Dispersion value

5.1

Notes
[34] - Point estimates, lower and upper confidence limits represent percentages. The mean difference and standard error of the mean is the percentage difference and standard error of the percentage difference.

Percentage of Participants with First BPAR

Statistical analysis description

Month 24

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[35]

P-value

= 0.9106

Method

Wald Test

Parameter type

Mean difference (final values)

Point estimate

0.6

Confidence interval

level

60%

sides

2-sided

lower limit

-3.88

upper limit

5.08

Variability estimate

Standard error of the mean

Dispersion value

5.32

Notes
[35] - Point estimates, lower and upper confidence limits represent percentages. The mean difference and standard error of the mean is the percentage difference and standard error of the percentage difference.

Percentage of Participants with First BPAR

Statistical analysis description

Month 24

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[36]

P-value

= 0.696

Method

Wald Test

Parameter type

Mean difference (final values)

Point estimate

-1.99

Confidence interval

level

60%

sides

2-sided

lower limit

-6.29

upper limit

2.3

Variability estimate

Standard error of the mean

Dispersion value

5.1

Notes
[36] - Point estimates, lower and upper confidence limits represent percentages. The mean difference and standard error of the mean is the percentage difference and standard error of the percentage difference.

Percentage of Participants with First BPAR

Statistical analysis description

Month 30

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[37]

P-value

= 0.9106

Method

Wald Test

Parameter type

Mean difference (final values)

Point estimate

0.6

Confidence interval

level

60%

sides

2-sided

lower limit

-3.88

upper limit

5.08

Variability estimate

Standard error of the mean

Dispersion value

5.32

Notes
[37] - Point estimates, lower and upper confidence limits represent percentages. The mean difference and standard error of the mean is the percentage difference and standard error of the percentage difference.

Percentage of Participants with First BPAR

Statistical analysis description

Month 30

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[38]

P-value

= 0.696

Method

Wald Test

Parameter type

Mean difference (final values)

Point estimate

-1.99

Confidence interval

level

60%

sides

2-sided

lower limit

-6.29

upper limit

2.3

Variability estimate

Standard error of the mean

Dispersion value

5.1

Notes
[38] - Point estimates, lower and upper confidence limits represent percentages. The mean difference and standard error of the mean is the percentage difference and standard error of the percentage difference.

Percentage of Participants with First BPAR

Statistical analysis description

Month 36

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[39]

P-value

= 0.8322

Method

Wald Test

Parameter type

Mean difference (final values)

Point estimate

-1.18

Confidence interval

level

60%

sides

2-sided

lower limit

-5.86

upper limit

3.5

Variability estimate

Standard error of the mean

Dispersion value

5.56

Notes
[39] - Point estimates, lower and upper confidence limits represent percentages. The mean difference and standard error of the mean is the percentage difference and standard error of the percentage difference.

Percentage of Participants with First BPAR

Statistical analysis description

Month 36

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[40]

P-value

= 0.4809

Method

Wald Test

Parameter type

Mean difference (final values)

Point estimate

-3.77

Confidence interval

level

60%

sides

2-sided

lower limit

-8.27

upper limit

0.73

Variability estimate

Standard error of the mean

Dispersion value

5.35

Notes
[40] - Point estimates, lower and upper confidence limits represent percentages. The mean difference and standard error of the mean is the percentage difference and standard error of the percentage difference.

Percentage of Participants with First BPAR

Statistical analysis description

Month 42

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[41]

P-value

= 0.5704

Method

Wald Test

Parameter type

Mean difference (final values)

Point estimate

-3.34

Confidence interval

level

60%

sides

2-sided

lower limit

-8.31

upper limit

1.62

Variability estimate

Standard error of the mean

Dispersion value

5.89

Notes
[41] - Point estimates, lower and upper confidence limits represent percentages. The mean difference and standard error of the mean is the percentage difference and standard error of the percentage difference.

Percentage of Participants with First BPAR

Statistical analysis description

Month 42

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[42]

P-value

= 0.2972

Method

Wald Test

Parameter type

Mean difference (final values)

Point estimate

-5.94

Confidence interval

level

60%

sides

2-sided

lower limit

-10.73

upper limit

-1.14

Variability estimate

Standard error of the mean

Dispersion value

5.7

Notes
[42] - Point estimates, lower and upper confidence limits represent percentages. The mean difference and standard error of the mean is the percentage difference and standard error of the percentage difference.

Percentage of Participants with First BPAR

Statistical analysis description

Month 48

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[43]

P-value

= 0.5704

Method

Wald Test

Parameter type

Mean difference (final values)

Point estimate

-3.34

Confidence interval

level

60%

sides

2-sided

lower limit

-8.31

upper limit

1.62

Variability estimate

Standard error of the mean

Dispersion value

5.89

Notes
[43] - Point estimates, lower and upper confidence limits represent percentages. The mean difference and standard error of the mean is the percentage difference and standard error of the percentage difference.

Percentage of Participants with First BPAR

Statistical analysis description

Month 48

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[44]

P-value

= 0.2972

Method

Wald Test

Parameter type

Mean difference (final values)

Point estimate

-5.94

Confidence interval

level

60%

sides

2-sided

lower limit

-10.73

upper limit

-1.14

Variability estimate

Standard error of the mean

Dispersion value

5.7

Notes
[44] - Point estimates, lower and upper confidence limits represent percentages. The mean difference and standard error of the mean is the percentage difference and standard error of the percentage difference.

Percentage of Participants with First BPAR

Statistical analysis description

Month 54

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[45]

P-value

= 0.5704

Method

Wald Test

Parameter type

Mean difference (final values)

Point estimate

-3.34

Confidence interval

level

60%

sides

2-sided

lower limit

-8.31

upper limit

1.62

Variability estimate

Standard error of the mean

Dispersion value

5.89

Notes
[45] - Point estimates, lower and upper confidence limits represent percentages. The mean difference and standard error of the mean is the percentage difference and standard error of the percentage difference.

Percentage of Participants with First BPAR

Statistical analysis description

Month 54

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[46]

P-value

= 0.2972

Method

Wald Test

Parameter type

Mean difference (final values)

Point estimate

-5.94

Confidence interval

level

60%

sides

2-sided

lower limit

-10.73

upper limit

-1.14

Variability estimate

Standard error of the mean

Dispersion value

5.7

Notes
[46] - Point estimates, lower and upper confidence limits represent percentages. The mean difference and standard error of the mean is the percentage difference and standard error of the percentage difference.

Percentage of Participants with First BPAR

Statistical analysis description

Month 60

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[47]

P-value

= 0.5704

Method

Wald Test

Parameter type

Mean difference (final values)

Point estimate

-3.34

Confidence interval

level

60%

sides

2-sided

lower limit

-8.31

upper limit

1.62

Variability estimate

Standard error of the mean

Dispersion value

5.89

Notes
[47] - Point estimates, lower and upper confidence limits represent percentages. The mean difference and standard error of the mean is the percentage difference and standard error of the percentage difference.

Percentage of Participants with First BPAR

Statistical analysis description

Month 60

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[48]

P-value

= 0.2972

Method

Wald Test

Parameter type

Mean difference (final values)

Point estimate

-5.94

Confidence interval

level

60%

sides

2-sided

lower limit

-10.73

upper limit

-1.14

Variability estimate

Standard error of the mean

Dispersion value

5.7

Notes
[48] - Point estimates, lower and upper confidence limits represent percentages. The mean difference and standard error of the mean is the percentage difference and standard error of the percentage difference.

Percentage of Participants with First BPAR

Statistical analysis description

Month 66

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[49]

P-value

= 0.5704

Method

Wald Test

Parameter type

Mean difference (final values)

Point estimate

-3.34

Confidence interval

level

60%

sides

2-sided

lower limit

-8.31

upper limit

1.62

Variability estimate

Standard error of the mean

Dispersion value

5.89

Notes
[49] - Point estimates, lower and upper confidence limits represent percentages. The mean difference and standard error of the mean is the percentage difference and standard error of the percentage difference.

Percentage of Participants with First BPAR

Statistical analysis description

Month 66

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[50]

P-value

= 0.2972

Method

Wald Test

Parameter type

Mean difference (final values)

Point estimate

-5.94

Confidence interval

level

60%

sides

2-sided

lower limit

-10.73

upper limit

-1.14

Variability estimate

Standard error of the mean

Dispersion value

5.7

Notes
[50] - Point estimates, lower and upper confidence limits represent percentages. The mean difference and standard error of the mean is the percentage difference and standard error of the percentage difference.

Percentage of Participants with First BPAR

Statistical analysis description

Month 72

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[51]

P-value

= 0.5704

Method

Wald Test

Parameter type

Mean difference (final values)

Point estimate

-3.34

Confidence interval

level

60%

sides

2-sided

lower limit

-8.31

upper limit

1.62

Variability estimate

Standard error of the mean

Dispersion value

5.89

Notes
[51] - Point estimates, lower and upper confidence limits represent percentages. The mean difference and standard error of the mean is the percentage difference and standard error of the percentage difference.

Percentage of Participants with First BPAR

Statistical analysis description

Month 72

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[52]

P-value

= 0.2972

Method

Wald Test

Parameter type

Mean difference (final values)

Point estimate

-5.94

Confidence interval

level

60%

sides

2-sided

lower limit

-10.73

upper limit

-1.14

Variability estimate

Standard error of the mean

Dispersion value

5.7

Notes
[52] - Point estimates, lower and upper confidence limits represent percentages. The mean difference and standard error of the mean is the percentage difference and standard error of the percentage difference.

Percentage of Participants with First BPAR

Statistical analysis description

Month 12

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[53]

P-value

= 0.4455

Method

Wald Test

Parameter type

Mean difference (final values)

Point estimate

3.75

Confidence interval

level

60%

sides

2-sided

lower limit

-0.39

upper limit

7.89

Variability estimate

Standard error of the mean

Dispersion value

4.91

Notes
[53] - Point estimates, lower and upper confidence limits represent percentages. The mean difference and standard error of the mean is the percentage difference and standard error of the percentage difference.

Percentage of Participants with First BPAR

Statistical analysis description

Month 12

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[54]

P-value

= 0.873

Method

Wald Test

Parameter type

Mean difference (final values)

Point estimate

-0.69

Confidence interval

level

60%

sides

2-sided

lower limit

-4.35

upper limit

2.96

Variability estimate

Standard error of the mean

Dispersion value

4.34

Notes
[54] - Point estimates, lower and upper confidence limits represent percentages. The mean difference and standard error of the mean is the percentage difference and standard error of the percentage difference.

Primary: Kaplan-Meier Analysis of Percentage of Participants with Treated Clinical Acute Rejection (TCAR) by Visit

Top of page

End point title

Kaplan-Meier Analysis of Percentage of Participants with Treated Clinical Acute Rejection (TCAR) by Visit

End point description

Treated clinical acute rejection (TCAR) was defined as an acute rejection episode that was diagnosed based on local biopsy readout and received anti-rejection treatment. The 'Number' and 'Confidence Interval 60%' columns represent cumulative proportions and 60% CIs as estimated from the fitted Kaplan-Meier curves for each treatment at scheduled visits..

End point type

Primary

End point timeframe

Months 12, 15, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72

End point values	Cyclosporine (CsA)	Tofacitinib Less Intensive (LI)	Tofacitinib More Intensive (MI)
Number of subjects analysed	64	60	54
Units: Percentage of Participants
number (confidence interval 60%)
Month 12 (n=55,56,49)	14.06 (10.41 to 17.72)	6.67 (3.96 to 9.38)	9.26 (5.94 to 12.58)
Month 15 (n=53,56,48)	17.19 (13.22 to 21.16)	6.67 (3.96 to 9.38)	11.11 (7.51 to 14.71)
Month 18 (n=51,54,46)	18.75 (14.64 to 22.86)	10 (6.74 to 13.26)	11.11 (7.51 to 14.71)
Month 24 (n=49,52,40)	18.75 (14.64 to 22.86)	11.67 (8.18 to 15.15)	11.11 (7.51 to 14.71)
Month 30 (n=46,37,27)	20.48 (16.21 to 24.75)	11.67 (8.18 to 15.15)	11.11 (7.51 to 14.71)
Month 36 (n=42,29,14)	23.94 (19.38 to 28.49)	11.67 (8.18 to 15.15)	11.11 (7.51 to 14.71)
Month 42 (n=36,29,13)	27.56 (22.74 to 32.38)	11.67 (8.18 to 15.15)	11.11 (7.51 to 14.71)
Month 48 (n=34,29,13)	27.56 (22.74 to 32.38)	11.67 (8.18 to 15.15)	11.11 (7.51 to 14.71)
Month 54 (n=33,28,12)	29.69 (24.69 to 34.69)	11.67 (8.18 to 15.15)	11.11 (7.51 to 14.71)
Month 60 (n=30,24,11)	29.69 (24.69 to 34.69)	11.67 (8.18 to 15.15)	11.11 (7.51 to 14.71)
Month 66 (n=25,21,9)	29.69 (24.69 to 34.69)	11.67 (8.18 to 15.15)	11.11 (7.51 to 14.71)
Month 72 (n=22,18,9)	29.69 (24.69 to 34.69)	11.67 (8.18 to 15.15)	11.11 (7.51 to 14.71)

Percentage of Participants with TCAR by Visit

Statistical analysis description

Month 15

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[55]

P-value

= 0.0654

Method

Wald Test

Parameter type

Mean difference (final values)

Point estimate

-10.52

Confidence interval

level

60%

sides

2-sided

lower limit

-15.33

upper limit

-5.71

Variability estimate

Standard error of the mean

Dispersion value

5.71

Notes
[55] - Point estimates, lower and upper confidence limits represent percentages. The mean difference and standard error of the mean is the percentage difference and standard error of the percentage difference.

Percentage of Participants with TCAR by Visit

Statistical analysis description

Month 15

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[56]

P-value

= 0.3398

Method

Wald Test

Parameter type

Mean difference (final values)

Point estimate

-6.08

Confidence interval

level

60%

sides

2-sided

lower limit

-11.43

upper limit

-0.72

Variability estimate

Standard error of the mean

Dispersion value

6.37

Notes
[56] - Point estimates, lower and upper confidence limits represent percentages. The mean difference and standard error of the mean is the percentage difference and standard error of the percentage difference.

Percentage of Participants with TCAR by Visit

Statistical analysis description

Month 18

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[57]

P-value

= 0.1601

Method

Wald Test

Parameter type

Mean difference (final values)

Point estimate

-8.75

Confidence interval

level

60%

sides

2-sided

lower limit

-13.99

upper limit

-3.51

Variability estimate

Standard error of the mean

Dispersion value

6.23

Notes
[57] - Point estimates, lower and upper confidence limits represent percentages. The mean difference and standard error of the mean is the percentage difference and standard error of the percentage difference.

Percentage of Participants with TCAR by Visit

Statistical analysis description

Month 18

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[58]

P-value

= 0.239

Method

Wald Test

Parameter type

Mean difference (final values)

Point estimate

-7.64

Confidence interval

level

60%

sides

2-sided

lower limit

-13.1

upper limit

-2.18

Variability estimate

Standard error of the mean

Dispersion value

6.49

Notes
[58] - Point estimates, lower and upper confidence limits represent percentages. The mean difference and standard error of the mean is the percentage difference and standard error of the percentage difference.

Percentage of Participants with TCAR by Visit

Statistical analysis description

Month 24

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[59]

P-value

= 0.2685

Method

Wald Test

Parameter type

Mean difference (final values)

Point estimate

-7.08

Confidence interval

level

60%

sides

2-sided

lower limit

-12.47

upper limit

-1.7

Variability estimate

Standard error of the mean

Dispersion value

6.4

Notes
[59] - Point estimates, lower and upper confidence limits represent percentages. The mean difference and standard error of the mean is the percentage difference and standard error of the percentage difference.

Percentage of Participants with TCAR by Visit

Statistical analysis description

Month 24

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[60]

P-value

= 0.239

Method

Wald Test

Parameter type

Mean difference (final values)

Point estimate

-7.64

Confidence interval

level

60%

sides

2-sided

lower limit

-13.1

upper limit

-2.18

Variability estimate

Standard error of the mean

Dispersion value

6.49

Notes
[60] - Point estimates, lower and upper confidence limits represent percentages. The mean difference and standard error of the mean is the percentage difference and standard error of the percentage difference.

Percentage of Participants with TCAR by Visit

Statistical analysis description

Month 30

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[61]

P-value

= 0.1785

Method

Wald Test

Parameter type

Mean difference (final values)

Point estimate

-8.81

Confidence interval

level

60%

sides

2-sided

lower limit

-14.32

upper limit

-3.3

Variability estimate

Standard error of the mean

Dispersion value

6.55

Notes
[61] - Point estimates, lower and upper confidence limits represent percentages. The mean difference and standard error of the mean is the percentage difference and standard error of the percentage difference.

Percentage of Participants with TCAR by Visit

Statistical analysis description

Month 30

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[62]

P-value

= 0.158

Method

Wald Test

Parameter type

Mean difference (final values)

Point estimate

-9.37

Confidence interval

level

60%

sides

2-sided

lower limit

-14.95

upper limit

-3.78

Variability estimate

Standard error of the mean

Dispersion value

6.63

Notes
[62] - Point estimates, lower and upper confidence limits represent percentages. The mean difference and standard error of the mean is the percentage difference and standard error of the percentage difference.

Percentage of Participants with TCAR by Visit

Statistical analysis description

Month 36

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[63]

P-value

= 0.0718

Method

Wald Test

Parameter type

Mean difference (final values)

Point estimate

-12.27

Confidence interval

level

60%

sides

2-sided

lower limit

-18

upper limit

-6.53

Variability estimate

Standard error of the mean

Dispersion value

6.81

Notes
[63] - Point estimates, lower and upper confidence limits represent percentages. The mean difference and standard error of the mean is the percentage difference and standard error of the percentage difference.

Percentage of Participants with TCAR by Visit

Statistical analysis description

Month 36

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[64]

P-value

= 0.0629

Method

Wald Test

Parameter type

Mean difference (final values)

Point estimate

-12.83

Confidence interval

level

60%

sides

2-sided

lower limit

-18.63

upper limit

-7.02

Variability estimate

Standard error of the mean

Dispersion value

6.9

Notes
[64] - Point estimates, lower and upper confidence limits represent percentages. The mean difference and standard error of the mean is the percentage difference and standard error of the percentage difference.

Percentage of Participants with TCAR by Visit

Statistical analysis description

Month 42

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[65]

P-value

= 0.0246

Method

Wald Test

Parameter type

Mean difference (final values)

Point estimate

-15.89

Confidence interval

level

60%

sides

2-sided

lower limit

-21.84

upper limit

-9.94

Variability estimate

Standard error of the mean

Dispersion value

7.07

Notes
[65] - Point estimates, lower and upper confidence limits represent percentages. The mean difference and standard error of the mean is the percentage difference and standard error of the percentage difference.

Percentage of Participants with TCAR by Visit

Statistical analysis description

Month 42

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[66]

P-value

= 0.0214

Method

Wald Test

Parameter type

Mean difference (final values)

Point estimate

-16.45

Confidence interval

level

60%

sides

2-sided

lower limit

-22.46

upper limit

-10.43

Variability estimate

Standard error of the mean

Dispersion value

7.15

Notes
[66] - Point estimates, lower and upper confidence limits represent percentages. The mean difference and standard error of the mean is the percentage difference and standard error of the percentage difference.

Percentage of Participants with TCAR by Visit

Statistical analysis description

Month 48

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[67]

P-value

= 0.0246

Method

Wald Test

Parameter type

Mean difference (final values)

Point estimate

-15.89

Confidence interval

level

60%

sides

2-sided

lower limit

-21.84

upper limit

-9.94

Variability estimate

Standard error of the mean

Dispersion value

7.07

Notes
[67] - Point estimates, lower and upper confidence limits represent percentages. The mean difference and standard error of the mean is the percentage difference and standard error of the percentage difference.

Percentage of Participants with TCAR by Visit

Statistical analysis description

Month 48

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[68]

P-value

= 0.0214

Method

Wald Test

Parameter type

Mean difference (final values)

Point estimate

-16.45

Confidence interval

level

60%

sides

2-sided

lower limit

-22.46

upper limit

-10.43

Variability estimate

Standard error of the mean

Dispersion value

7.15

Notes
[68] - Point estimates, lower and upper confidence limits represent percentages. The mean difference and standard error of the mean is the percentage difference and standard error of the percentage difference.

Percentage of Participants with TCAR by Visit

Statistical analysis description

Month 54

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[69]

P-value

= 0.0128

Method

Wald Test

Parameter type

Mean difference (final values)

Point estimate

-18.02

Confidence interval

level

60%

sides

2-sided

lower limit

-24.12

upper limit

-11.93

Variability estimate

Standard error of the mean

Dispersion value

7.24

Notes
[69] - Point estimates, lower and upper confidence limits represent percentages. The mean difference and standard error of the mean is the percentage difference and standard error of the percentage difference.

Percentage of Participants with TCAR by Visit

Statistical analysis description

Month 54

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[70]

P-value

= 0.0111

Method

Wald Test

Parameter type

Mean difference (final values)

Point estimate

-18.58

Confidence interval

level

60%

sides

2-sided

lower limit

-24.74

upper limit

-12.42

Variability estimate

Standard error of the mean

Dispersion value

7.32

Notes
[70] - Point estimates, lower and upper confidence limits represent percentages. The mean difference and standard error of the mean is the percentage difference and standard error of the percentage difference.

Percentage of Participants with TCAR by Visit

Statistical analysis description

Month 60

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[71]

P-value

= 0.0128

Method

Wald Test

Parameter type

Mean difference (final values)

Point estimate

-18.02

Confidence interval

level

60%

sides

2-sided

lower limit

-24.12

upper limit

-11.93

Variability estimate

Standard error of the mean

Dispersion value

7.24

Notes
[71] - Point estimates, lower and upper confidence limits represent percentages. The mean difference and standard error of the mean is the percentage difference and standard error of the percentage difference.

Percentage of Participants with TCAR by Visit

Statistical analysis description

Month 60

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[72]

P-value

= 0.0111

Method

Wald Test

Parameter type

Mean difference (final values)

Point estimate

-18.58

Confidence interval

level

60%

sides

2-sided

lower limit

-24.74

upper limit

-12.42

Variability estimate

Standard error of the mean

Dispersion value

7.32

Notes
[72] - Point estimates, lower and upper confidence limits represent percentages. The mean difference and standard error of the mean is the percentage difference and standard error of the percentage difference.

Percentage of Participants with TCAR by Visit

Statistical analysis description

Month 66

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[73]

P-value

= 0.0128

Method

Wald Test

Parameter type

Mean difference (final values)

Point estimate

-18.02

Confidence interval

level

60%

sides

2-sided

lower limit

-24.12

upper limit

-11.93

Variability estimate

Standard error of the mean

Dispersion value

7.24

Notes
[73] - Point estimates, lower and upper confidence limits represent percentages. The mean difference and standard error of the mean is the percentage difference and standard error of the percentage difference.

Percentage of Participants with TCAR by Visit

Statistical analysis description

Month 66

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[74]

P-value

= 0.0111

Method

Wald Test

Parameter type

Mean difference (final values)

Point estimate

-18.58

Confidence interval

level

60%

sides

2-sided

lower limit

-24.74

upper limit

-12.42

Variability estimate

Standard error of the mean

Dispersion value

7.32

Notes
[74] - Point estimates, lower and upper confidence limits represent percentages. The mean difference and standard error of the mean is the percentage difference and standard error of the percentage difference.

Percentage of Participants with TCAR by Visit

Statistical analysis description

Month 72

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[75]

P-value

= 0.0128

Method

Wald Test

Parameter type

Mean difference (final values)

Point estimate

-18.02

Confidence interval

level

60%

sides

2-sided

lower limit

-24.12

upper limit

-11.93

Variability estimate

Standard error of the mean

Dispersion value

7.24

Notes
[75] - Point estimates, lower and upper confidence limits represent percentages. The mean difference and standard error of the mean is the percentage difference and standard error of the percentage difference.

Percentage of Participants with TCAR by Visit

Statistical analysis description

Month 72

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[76]

P-value

= 0.0111

Method

Wald Test

Parameter type

Mean difference (final values)

Point estimate

-18.58

Confidence interval

level

60%

sides

2-sided

lower limit

-24.74

upper limit

-12.42

Variability estimate

Standard error of the mean

Dispersion value

7.32

Notes
[76] - Point estimates, lower and upper confidence limits represent percentages. The mean difference and standard error of the mean is the percentage difference and standard error of the percentage difference.

Percentage of Participants with TCAR by Visit

Statistical analysis description

Month 12

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[77]

P-value

= 0.1715

Method

Wald Test

Parameter type

Mean difference (final values)

Point estimate

-7.4

Confidence interval

level

60%

sides

2-sided

lower limit

-11.95

upper limit

-2.84

Variability estimate

Standard error of the mean

Dispersion value

5.41

Notes
[77] - Point estimates, lower and upper confidence limits represent percentages. The mean difference and standard error of the mean is the percentage difference and standard error of the percentage difference.

Percentage of Participants with TCAR by Visit

Statistical analysis description

Month 12

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[78]

P-value

= 0.4131

Method

Wald Test

Parameter type

Mean difference (final values)

Point estimate

-4.8

Confidence interval

level

60%

sides

2-sided

lower limit

-9.74

upper limit

0.14

Variability estimate

Standard error of the mean

Dispersion value

5.87

Notes
[78] - Point estimates, lower and upper confidence limits represent percentages. The mean difference and standard error of the mean is the percentage difference and standard error of the percentage difference.

Secondary: Kaplan-Meier Analysis of Percentage of Participants with Efficacy Failure by Visit

Top of page

End point title

Kaplan-Meier Analysis of Percentage of Participants with Efficacy Failure by Visit

End point description

Efficacy failure was the first occurrence of BPAR diagnosed by the central pathologist or graft loss including participant death. BPAR (category acute rejection) was interpreted by the central blinded pathologist according to the Banff 97 working classification. The 'Number' and 'Confidence Interval 60%' columns represent cumulative proportions and 60% CIs as estimated from the fitted Kaplan-Meier curves for each treatment at scheduled visits.

End point type

Secondary

End point timeframe

Months 12, 15, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72

End point values	Cyclosporine (CsA)	Tofacitinib Less Intensive (LI)	Tofacitinib More Intensive (MI)
Number of subjects analysed	64	60	54
Units: Percentage of Participants
number (confidence interval 60%)
Month 12 (n=60,54,51)	6.25 (3.7 to 8.8)	10 (6.74 to 13.26)	5.56 (2.93 to 8.18)
Month 15 (n=58,54,49)	7.81 (4.99 to 10.64)	10 (6.74 to 13.26)	9.26 (5.94 to 12.58)
Month 18 (n=56,54,49)	10.99 (7.69 to 14.29)	10 (6.74 to 13.26)	9.26 (5.94 to 12.58)
Month 24 (n=54,54,46)	10.99 (7.69 to 14.29)	10 (6.74 to 13.26)	14.81 (10.75 to 18.88)
Month 30 (n=53,52,46)	12.64 (9.12 to 16.16)	10 (6.74 to 13.26)	14.81 (10.75 to 18.88)
Month 36 (n=51,48,42)	15.94 (12.04 to 19.83)	15.19 (11.26 to 19.12)	16.71 (12.43 to 20.99)
Month 42 (n=44,47,41)	19.59 (15.3 to 23.88)	15.19 (11.26 to 19.12)	18.69 (14.2 to 23.18)
Month 48 (n=43,44,38)	21.42 (16.96 to 25.88)	18.84 (14.52 to 23.16)	18.69 (14.2 to 23.18)
Month 54 (n=41,44,36)	23.25 (18.63 to 27.86)	18.84 (14.52 to 23.16)	18.69 (14.2 to 23.18)
Month 60 (n=41,44,35)	23.25 (18.63 to 27.86)	18.84 (14.52 to 23.16)	20.95 (16.2 to 25.7)
Month 66 (n=39,42,29)	23.25 (18.63 to 27.86)	18.84 (14.52 to 23.16)	20.95 (16.2 to 25.7)
Month 72 (n=35,28,19)	23.25 (18.63 to 27.86)	22.81 (18.1 to 27.51)	20.95 (16.2 to 25.7)

Percentage of Participants with Efficacy Failure

Statistical analysis description

Month 15

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[79]

P-value

= 0.6694

Method

Wald Test

Parameter type

Mean difference (final values)

Point estimate

2.19

Confidence interval

level

60%

sides

2-sided

lower limit

-2.12

upper limit

6.5

Variability estimate

Standard error of the mean

Dispersion value

5.12

Notes
[79] - Point estimates, lower and upper confidence limits represent percentages. The mean difference and standard error of the mean is the percentage difference and standard error of the percentage difference.

Percentage of Participants with Efficacy Failure

Statistical analysis description

Month 15

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[80]

P-value

= 0.7799

Method

Wald Test

Parameter type

Mean difference (final values)

Point estimate

1.45

Confidence interval

level

60%

sides

2-sided

lower limit

-2.91

upper limit

5.8

Variability estimate

Standard error of the mean

Dispersion value

5.18

Notes
[80] - Point estimates, lower and upper confidence limits represent percentages. The mean difference and standard error of the mean is the percentage difference and standard error of the percentage difference.

Percentage of Participants with Efficacy Failure

Statistical analysis description

Month 18

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[81]

P-value

= 0.8572

Method

Wald Test

Parameter type

Mean difference (final values)

Point estimate

-0.99

Confidence interval

level

60%

sides

2-sided

lower limit

-5.63

upper limit

3.65

Variability estimate

Standard error of the mean

Dispersion value

5.51

Notes
[81] - Point estimates, lower and upper confidence limits represent percentages. The mean difference and standard error of the mean is the percentage difference and standard error of the percentage difference.

Percentage of Participants with Efficacy Failure

Statistical analysis description

Month 18

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[82]

P-value

= 0.7555

Method

Wald Test

Parameter type

Mean difference (final values)

Point estimate

-1.73

Confidence interval

level

60%

sides

2-sided

lower limit

-6.41

upper limit

2.95

Variability estimate

Standard error of the mean

Dispersion value

5.56

Notes
[82] - Point estimates, lower and upper confidence limits represent percentages. The mean difference and standard error of the mean is the percentage difference and standard error of the percentage difference.

Percentage of Participants with Efficacy Failure

Statistical analysis description

Month 24

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[83]

P-value

= 0.8572

Method

Wald Test

Parameter type

Mean difference (final values)

Point estimate

-0.99

Confidence interval

level

60%

sides

2-sided

lower limit

-5.63

upper limit

3.65

Variability estimate

Standard error of the mean

Dispersion value

5.51

Notes
[83] - Point estimates, lower and upper confidence limits represent percentages. The mean difference and standard error of the mean is the percentage difference and standard error of the percentage difference.

Percentage of Participants with Efficacy Failure

Statistical analysis description

Month 24

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[84]

P-value

= 0.539

Method

Wald Test

Parameter type

Mean difference (final values)

Point estimate

3.82

Confidence interval

level

60%

sides

2-sided

lower limit

-1.41

upper limit

9.06

Variability estimate

Standard error of the mean

Dispersion value

6.22

Notes
[84] - Point estimates, lower and upper confidence limits represent percentages. The mean difference and standard error of the mean is the percentage difference and standard error of the percentage difference.

Percentage of Participants with Efficacy Failure

Statistical analysis description

Month 30

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[85]

P-value

= 0.6432

Method

Wald Test

Parameter type

Mean difference (final values)

Point estimate

-2.64

Confidence interval

level

60%

sides

2-sided

lower limit

-7.44

upper limit

2.16

Variability estimate

Standard error of the mean

Dispersion value

5.7

Notes
[85] - Point estimates, lower and upper confidence limits represent percentages. The mean difference and standard error of the mean is the percentage difference and standard error of the percentage difference.

Percentage of Participants with Efficacy Failure

Statistical analysis description

Month 30

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[86]

P-value

= 0.7336

Method

Wald Test

Parameter type

Mean difference (final values)

Point estimate

2.18

Confidence interval

level

60%

sides

2-sided

lower limit

-3.2

upper limit

7.55

Variability estimate

Standard error of the mean

Dispersion value

6.39

Notes
[86] - Point estimates, lower and upper confidence limits represent percentages. The mean difference and standard error of the mean is the percentage difference and standard error of the percentage difference.

Percentage of Participants with Efficacy Failure

Statistical analysis description

Month 36

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[87]

P-value

= 0.9099

Method

Wald Test

Parameter type

Mean difference (final values)

Point estimate

-0.74

Confidence interval

level

60%

sides

2-sided

lower limit

-6.28

upper limit

4.79

Variability estimate

Standard error of the mean

Dispersion value

6.57

Notes
[87] - Point estimates, lower and upper confidence limits represent percentages. The mean difference and standard error of the mean is the percentage difference and standard error of the percentage difference.

Percentage of Participants with Efficacy Failure

Statistical analysis description

Month 36

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[88]

P-value

= 0.9106

Method

Wald Test

Parameter type

Mean difference (final values)

Point estimate

0.77

Confidence interval

level

60%

sides

2-sided

lower limit

-5.01

upper limit

6.56

Variability estimate

Standard error of the mean

Dispersion value

6.87

Notes
[88] - Point estimates, lower and upper confidence limits represent percentages. The mean difference and standard error of the mean is the percentage difference and standard error of the percentage difference.

Percentage of Participants with Efficacy Failure

Statistical analysis description

Month 42

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[89]

P-value

= 0.5244

Method

Wald Test

Parameter type

Mean difference (final values)

Point estimate

-4.4

Confidence interval

level

60%

sides

2-sided

lower limit

-10.22

upper limit

1.42

Variability estimate

Standard error of the mean

Dispersion value

6.91

Notes
[89] - Point estimates, lower and upper confidence limits represent percentages. The mean difference and standard error of the mean is the percentage difference and standard error of the percentage difference.

Percentage of Participants with Efficacy Failure

Statistical analysis description

Month 42

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[90]

P-value

= 0.9029

Method

Wald Test

Parameter type

Mean difference (final values)

Point estimate

-0.9

Confidence interval

level

60%

sides

2-sided

lower limit

-7.11

upper limit

5.31

Variability estimate

Standard error of the mean

Dispersion value

7.38

Notes
[90] - Point estimates, lower and upper confidence limits represent percentages. The mean difference and standard error of the mean is the percentage difference and standard error of the percentage difference.

Percentage of Participants with Efficacy Failure

Statistical analysis description

Month 48

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[91]

P-value

= 0.7267

Method

Wald Test

Parameter type

Mean difference (final values)

Point estimate

-2.58

Confidence interval

level

60%

sides

2-sided

lower limit

-8.78

upper limit

3.63

Variability estimate

Standard error of the mean

Dispersion value

7.38

Notes
[91] - Point estimates, lower and upper confidence limits represent percentages. The mean difference and standard error of the mean is the percentage difference and standard error of the percentage difference.

Percentage of Participants with Efficacy Failure

Statistical analysis description

Month 48

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[92]

P-value

= 0.7168

Method

Wald Test

Parameter type

Mean difference (final values)

Point estimate

-2.73

Confidence interval

level

60%

sides

2-sided

lower limit

-9.06

upper limit

3.6

Variability estimate

Standard error of the mean

Dispersion value

7.52

Notes
[92] - Point estimates, lower and upper confidence limits represent percentages. The mean difference and standard error of the mean is the percentage difference and standard error of the percentage difference.

Percentage of Participants with Efficacy Failure

Statistical analysis description

Month 54

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[93]

P-value

= 0.5574

Method

Wald Test

Parameter type

Mean difference (final values)

Point estimate

-4.4

Confidence interval

level

60%

sides

2-sided

lower limit

-10.72

upper limit

1.91

Variability estimate

Standard error of the mean

Dispersion value

7.51

Notes
[93] - Point estimates, lower and upper confidence limits represent percentages. The mean difference and standard error of the mean is the percentage difference and standard error of the percentage difference.

Percentage of Participants with Efficacy Failure

Statistical analysis description

Month 54

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[94]

P-value

= 0.5515

Method

Wald Test

Parameter type

Mean difference (final values)

Point estimate

-4.56

Confidence interval

level

60%

sides

2-sided

lower limit

-10.99

upper limit

1.88

Variability estimate

Standard error of the mean

Dispersion value

7.65

Notes
[94] - Point estimates, lower and upper confidence limits represent percentages. The mean difference and standard error of the mean is the percentage difference and standard error of the percentage difference.

Percentage of Participants with Efficacy Failure

Statistical analysis description

Month 60

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[95]

P-value

= 0.5574

Method

Wald Test

Parameter type

Mean difference (final values)

Point estimate

-4.4

Confidence interval

level

60%

sides

2-sided

lower limit

-10.72

upper limit

1.91

Variability estimate

Standard error of the mean

Dispersion value

7.51

Notes
[95] - Point estimates, lower and upper confidence limits represent percentages. The mean difference and standard error of the mean is the percentage difference and standard error of the percentage difference.

Percentage of Participants with Efficacy Failure

Statistical analysis description

Month 60

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[96]

P-value

= 0.7704

Method

Wald Test

Parameter type

Mean difference (final values)

Point estimate

-2.3

Confidence interval

level

60%

sides

2-sided

lower limit

-8.92

upper limit

4.33

Variability estimate

Standard error of the mean

Dispersion value

7.87

Notes
[96] - Point estimates, lower and upper confidence limits represent percentages. The mean difference and standard error of the mean is the percentage difference and standard error of the percentage difference.

Percentage of Participants with Efficacy Failure

Statistical analysis description

Month 66

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[97]

P-value

= 0.5574

Method

Wald Test

Parameter type

Mean difference (final values)

Point estimate

-4.4

Confidence interval

level

60%

sides

2-sided

lower limit

-10.72

upper limit

1.91

Variability estimate

Standard error of the mean

Dispersion value

7.51

Notes
[97] - Point estimates, lower and upper confidence limits represent percentages. The mean difference and standard error of the mean is the percentage difference and standard error of the percentage difference.

Percentage of Participants with Efficacy Failure

Statistical analysis description

Month 66

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[98]

P-value

= 0.7704

Method

Wald Test

Parameter type

Mean difference (final values)

Point estimate

-2.3

Confidence interval

level

60%

sides

2-sided

lower limit

-8.92

upper limit

4.33

Variability estimate

Standard error of the mean

Dispersion value

7.87

Notes
[98] - Point estimates, lower and upper confidence limits represent percentages. The mean difference and standard error of the mean is the percentage difference and standard error of the percentage difference.

Percentage of Participants with Efficacy Failure

Statistical analysis description

Month 72

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[99]

P-value

= 0.9551

Method

Wald Test

Parameter type

Mean difference (final values)

Point estimate

-0.44

Confidence interval

level

60%

sides

2-sided

lower limit

-7.03

upper limit

6.15

Variability estimate

Standard error of the mean

Dispersion value

7.83

Notes
[99] - Point estimates, lower and upper confidence limits represent percentages. The mean difference and standard error of the mean is the percentage difference and standard error of the percentage difference.

Percentage of Participants with Efficacy Failure

Statistical analysis description

Month 72

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[100]

P-value

= 0.7704

Method

Wald Test

Parameter type

Mean difference (final values)

Point estimate

-2.3

Confidence interval

level

60%

sides

2-sided

lower limit

-8.92

upper limit

4.33

Variability estimate

Standard error of the mean

Dispersion value

7.87

Notes
[100] - Point estimates, lower and upper confidence limits represent percentages. The mean difference and standard error of the mean is the percentage difference and standard error of the percentage difference.

Percentage of Participants with Efficacy Failure

Statistical analysis description

Month 12

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[101]

P-value

= 0.4455

Method

Wald Test

Parameter type

Mean difference (final values)

Point estimate

3.75

Confidence interval

level

60%

sides

2-sided

lower limit

-0.39

upper limit

7.89

Variability estimate

Standard error of the mean

Dispersion value

4.91

Notes
[101] - Point estimates, lower and upper confidence limits represent percentages. The mean difference and standard error of the mean is the percentage difference and standard error of the percentage difference.

Percentage of Participants with Efficacy Failure

Statistical analysis description

Month 12

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[102]

P-value

= 0.873

Method

Wald Test

Parameter type

Mean difference (final values)

Point estimate

-0.69

Confidence interval

level

60%

sides

2-sided

lower limit

-4.35

upper limit

2.96

Variability estimate

Standard error of the mean

Dispersion value

4.34

Notes
[102] - Point estimates, lower and upper confidence limits represent percentages. The mean difference and standard error of the mean is the percentage difference and standard error of the percentage difference.

Secondary: Kaplan-Meier Analysis of Percentage of Participants with Combined Banff Rejection (BR) by Visit

Top of page

End point title

Kaplan-Meier Analysis of Percentage of Participants with Combined Banff Rejection (BR) by Visit

End point description

Banff 97: standard classification for scoring and classifying rejection of kidney transplant biopsies in 6 diagnostic categories: normal, antibody-mediated rejection, borderline changes: ‘suspicious’ for acute cellular rejection, acute/active cellular rejection, chronic/sclerosing allograft nephropathy, and other. Combined Banff rejection calculated from categories of antibody-mediated rejection (Category 2) plus borderline changes (Category 3) plus acute rejection (Category 4), as interpreted by the central pathologist. The 'Number' and 'Confidence Interval 60%' columns represent cumulative proportions and 60% CIs as estimated from the fitted Kaplan-Meier curves for each treatment at scheduled visits.

End point type

Secondary

End point timeframe

Months 12, 15, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72

End point values	Cyclosporine (CsA)	Tofacitinib Less Intensive (LI)	Tofacitinib More Intensive (MI)
Number of subjects analysed	64	60	54
Units: Percentage of Participants
number (confidence interval 60%)
Month 12 (n=54,52,48)	15.63 (11.81 to 19.44)	13.33 (9.64 to 17.03)	11.11 (7.51 to 14.71)
Month 15 (n=51,52,45)	20.31 (16.08 to 24.55)	13.33 (9.64 to 17.03)	16.67 (12.4 to 20.93)
Month 18 (n=49,52,43)	21.91 (17.55 to 26.26)	13.33 (9.64 to 17.03)	16.67 (12.4 to 20.93)
Month 24 (n=46,50,37)	23.57 (19.09 to 28.05)	15 (11.12 to 18.88)	18.6 (14.13 to 23.07)
Month 30 (n=44,37,23)	23.57 (19.09 to 28.05)	15 (11.12 to 18.88)	21.41 (16.51 to 26.31)
Month 36 (n=41,28,12)	25.3 (20.69 to 29.92)	15 (11.12 to 18.88)	21.41 (16.51 to 26.31)
Month 42 (n=34,28,11)	27.44 (22.62 to 32.26)	15 (11.12 to 18.88)	21.41 (16.51 to 26.31)
Month 48 (n=33,28,11)	27.44 (22.62 to 32.26)	15 (11.12 to 18.88)	21.41 (16.51 to 26.31)
Month 54 (n=33,27,10)	27.44 (22.62 to 32.26)	15 (11.12 to 18.88)	21.41 (16.51 to 26.31)
Month 60 (n=31,23,9)	27.44 (22.62 to 32.26)	15 (11.12 to 18.88)	21.41 (16.51 to 26.31)
Month 66 (n=26,20,9)	27.44 (22.62 to 32.26)	15 (11.12 to 18.88)	21.41 (16.51 to 26.31)
Month 72 (n=24,18,9)	27.44 (22.62 to 32.26)	15 (11.12 to 18.88)	21.41 (16.51 to 26.31)

Percentage of Participants with Combined BR

Statistical analysis description

Month 15

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[103]

P-value

= 0.2957

Method

Wald Test

Parameter type

Mean difference (final values)

Point estimate

-6.98

Confidence interval

level

60%

sides

2-sided

lower limit

-12.6

upper limit

-1.36

Variability estimate

Standard error of the mean

Dispersion value

6.67

Notes
[103] - Point estimates, lower and upper confidence limits represent percentages. The mean difference and standard error of the mean is the percentage difference and standard error of the percentage difference.

Percentage of Participants with Combined BR

Statistical analysis description

Month 15

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[104]

P-value

= 0.6097

Method

Wald Test

Parameter type

Mean difference (final values)

Point estimate

-3.65

Confidence interval

level

60%

sides

2-sided

lower limit

-9.66

upper limit

2.37

Variability estimate

Standard error of the mean

Dispersion value

7.14

Notes
[104] - Point estimates, lower and upper confidence limits represent percentages. The mean difference and standard error of the mean is the percentage difference and standard error of the percentage difference.

Percentage of Participants with Combined BR

Statistical analysis description

Month 18

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[105]

P-value

= 0.2064

Method

Wald Test

Parameter type

Mean difference (final values)

Point estimate

-8.57

Confidence interval

level

60%

sides

2-sided

lower limit

-14.28

upper limit

-2.86

Variability estimate

Standard error of the mean

Dispersion value

6.79

Notes
[105] - Point estimates, lower and upper confidence limits represent percentages. The mean difference and standard error of the mean is the percentage difference and standard error of the percentage difference.

Percentage of Participants with Combined BR

Statistical analysis description

Month 18

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[106]

P-value

= 0.4696

Method

Wald Test

Parameter type

Mean difference (final values)

Point estimate

-5.24

Confidence interval

level

60%

sides

2-sided

lower limit

-11.34

upper limit

0.86

Variability estimate

Standard error of the mean

Dispersion value

7.25

Notes
[106] - Point estimates, lower and upper confidence limits represent percentages. The mean difference and standard error of the mean is the percentage difference and standard error of the percentage difference.

Percentage of Participants with Combined BR

Statistical analysis description

Month 24

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[107]

P-value

= 0.2238

Method

Wald Test

Parameter type

Mean difference (final values)

Point estimate

-8.57

Confidence interval

level

60%

sides

2-sided

lower limit

-14.5

upper limit

-2.64

Variability estimate

Standard error of the mean

Dispersion value

7.04

Notes
[107] - Point estimates, lower and upper confidence limits represent percentages. The mean difference and standard error of the mean is the percentage difference and standard error of the percentage difference.

Percentage of Participants with Combined BR

Statistical analysis description

Month 24

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[108]

P-value

= 0.5093

Method

Wald Test

Parameter type

Mean difference (final values)

Point estimate

-4.96

Confidence interval

level

60%

sides

2-sided

lower limit

-11.29

upper limit

1.37

Variability estimate

Standard error of the mean

Dispersion value

7.52

Notes
[108] - Point estimates, lower and upper confidence limits represent percentages. The mean difference and standard error of the mean is the percentage difference and standard error of the percentage difference.

Percentage of Participants with Combined BR

Statistical analysis description

Month 30

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[109]

P-value

= 0.2238

Method

Wald Test

Parameter type

Mean difference (final values)

Point estimate

-8.57

Confidence interval

level

60%

sides

2-sided

lower limit

-14.5

upper limit

-2.64

Variability estimate

Standard error of the mean

Dispersion value

7.04

Notes
[109] - Point estimates, lower and upper confidence limits represent percentages. The mean difference and standard error of the mean is the percentage difference and standard error of the percentage difference.

Percentage of Participants with Combined BR

Statistical analysis description

Month 30

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[110]

P-value

= 0.7846

Method

Wald Test

Parameter type

Mean difference (final values)

Point estimate

-2.16

Confidence interval

level

60%

sides

2-sided

lower limit

-8.8

upper limit

4.48

Variability estimate

Standard error of the mean

Dispersion value

7.89

Notes
[110] - Point estimates, lower and upper confidence limits represent percentages. The mean difference and standard error of the mean is the percentage difference and standard error of the percentage difference.

Percentage of Participants with Combined BR

Statistical analysis description

Month 36

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[111]

P-value

= 0.1501

Method

Wald Test

Parameter type

Mean difference (final values)

Point estimate

-10.3

Confidence interval

level

60%

sides

2-sided

lower limit

-16.33

upper limit

-4.28

Variability estimate

Standard error of the mean

Dispersion value

7.16

Notes
[111] - Point estimates, lower and upper confidence limits represent percentages. The mean difference and standard error of the mean is the percentage difference and standard error of the percentage difference.

Percentage of Participants with Combined BR

Statistical analysis description

Month 36

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[112]

P-value

= 0.6263

Method

Wald Test

Parameter type

Mean difference (final values)

Point estimate

-3.89

Confidence interval

level

60%

sides

2-sided

lower limit

-10.62

upper limit

2.84

Variability estimate

Standard error of the mean

Dispersion value

Notes
[112] - Point estimates, lower and upper confidence limits represent percentages. The mean difference and standard error of the mean is the percentage difference and standard error of the percentage difference.

Percentage of Participants with Combined BR

Statistical analysis description

Month 42

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[113]

P-value

= 0.0905

Method

Wald Test

Parameter type

Mean difference (final values)

Point estimate

-12.44

Confidence interval

level

60%

sides

2-sided

lower limit

-18.62

upper limit

-6.25

Variability estimate

Standard error of the mean

Dispersion value

7.35

Notes
[113] - Point estimates, lower and upper confidence limits represent percentages. The mean difference and standard error of the mean is the percentage difference and standard error of the percentage difference.

Percentage of Participants with Combined BR

Statistical analysis description

Month 42

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[114]

P-value

= 0.4604

Method

Wald Test

Parameter type

Mean difference (final values)

Point estimate

-6.03

Confidence interval

level

60%

sides

2-sided

lower limit

-12.9

upper limit

0.84

Variability estimate

Standard error of the mean

Dispersion value

8.16

Notes
[114] - Point estimates, lower and upper confidence limits represent percentages. The mean difference and standard error of the mean is the percentage difference and standard error of the percentage difference.

Percentage of Participants with Combined BR

Statistical analysis description

Month 48

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[115]

P-value

= 0.0905

Method

Wald Test

Parameter type

Mean difference (final values)

Point estimate

-12.44

Confidence interval

level

60%

sides

2-sided

lower limit

-18.62

upper limit

-6.25

Variability estimate

Standard error of the mean

Dispersion value

7.35

Notes
[115] - Point estimates, lower and upper confidence limits represent percentages. The mean difference and standard error of the mean is the percentage difference and standard error of the percentage difference.

Percentage of Participants with Combined BR

Statistical analysis description

Month 48

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[116]

P-value

= 0.4604

Method

Wald Test

Parameter type

Mean difference (final values)

Point estimate

-6.03

Confidence interval

level

60%

sides

2-sided

lower limit

-12.9

upper limit

0.84

Variability estimate

Standard error of the mean

Dispersion value

8.16

Notes
[116] - Point estimates, lower and upper confidence limits represent percentages. The mean difference and standard error of the mean is the percentage difference and standard error of the percentage difference.

Percentage of Participants with Combined BR

Statistical analysis description

Month 54

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[117]

P-value

= 0.0905

Method

Wald Test

Parameter type

Mean difference (final values)

Point estimate

-12.44

Confidence interval

level

60%

sides

2-sided

lower limit

-18.62

upper limit

-6.25

Variability estimate

Standard error of the mean

Dispersion value

7.35

Notes
[117] - Point estimates, lower and upper confidence limits represent percentages. The mean difference and standard error of the mean is the percentage difference and standard error of the percentage difference.

Percentage of Participants with Combined BR

Statistical analysis description

Month 54

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[118]

P-value

= 0.4604

Method

Wald Test

Parameter type

Mean difference (final values)

Point estimate

-6.03

Confidence interval

level

60%

sides

2-sided

lower limit

-12.9

upper limit

0.84

Variability estimate

Standard error of the mean

Dispersion value

8.16

Notes
[118] - Point estimates, lower and upper confidence limits represent percentages. The mean difference and standard error of the mean is the percentage difference and standard error of the percentage difference.

Percentage of Participants with Combined BR

Statistical analysis description

Month 60

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[119]

P-value

= 0.0905

Method

Wald Test

Parameter type

Mean difference (final values)

Point estimate

-12.44

Confidence interval

level

60%

sides

2-sided

lower limit

-18.62

upper limit

-6.25

Variability estimate

Standard error of the mean

Dispersion value

7.35

Notes
[119] - Point estimates, lower and upper confidence limits represent percentages. The mean difference and standard error of the mean is the percentage difference and standard error of the percentage difference.

Percentage of Participants with Combined BR

Statistical analysis description

Month 60

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[120]

P-value

= 0.4604

Method

Wald Test

Parameter type

Mean difference (final values)

Point estimate

-6.03

Confidence interval

level

60%

sides

2-sided

lower limit

-12.9

upper limit

0.84

Variability estimate

Standard error of the mean

Dispersion value

8.16

Notes
[120] - Point estimates, lower and upper confidence limits represent percentages. The mean difference and standard error of the mean is the percentage difference and standard error of the percentage difference.

Percentage of Participants with Combined BR

Statistical analysis description

Month 66

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[121]

P-value

= 0.0905

Method

Wald Test

Parameter type

Mean difference (final values)

Point estimate

-12.44

Confidence interval

level

60%

sides

2-sided

lower limit

-18.62

upper limit

-6.25

Variability estimate

Standard error of the mean

Dispersion value

7.35

Notes
[121] - Point estimates, lower and upper confidence limits represent percentages. The mean difference and standard error of the mean is the percentage difference and standard error of the percentage difference.

Percentage of Participants with Combined BR

Statistical analysis description

Month 66

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[122]

P-value

= 0.4604

Method

Wald Test

Parameter type

Mean difference (final values)

Point estimate

-6.03

Confidence interval

level

60%

sides

2-sided

lower limit

-12.9

upper limit

0.84

Variability estimate

Standard error of the mean

Dispersion value

8.16

Notes
[122] - Point estimates, lower and upper confidence limits represent percentages. The mean difference and standard error of the mean is the percentage difference and standard error of the percentage difference.

Percentage of Participants with Combined BR

Statistical analysis description

Month 72

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[123]

P-value

= 0.0905

Method

Wald Test

Parameter type

Mean difference (final values)

Point estimate

-12.44

Confidence interval

level

60%

sides

2-sided

lower limit

-18.62

upper limit

-6.25

Variability estimate

Standard error of the mean

Dispersion value

7.35

Notes
[123] - Point estimates, lower and upper confidence limits represent percentages. The mean difference and standard error of the mean is the percentage difference and standard error of the percentage difference.

Percentage of Participants with Combined BR

Statistical analysis description

Month 72

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[124]

P-value

= 0.4604

Method

Wald Test

Parameter type

Mean difference (final values)

Point estimate

-6.03

Confidence interval

level

60%

sides

2-sided

lower limit

-12.9

upper limit

0.84

Variability estimate

Standard error of the mean

Dispersion value

8.16

Notes
[124] - Point estimates, lower and upper confidence limits represent percentages. The mean difference and standard error of the mean is the percentage difference and standard error of the percentage difference.

Percentage of Participants with Combined BR

Statistical analysis description

Month 12

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[125]

P-value

= 0.7166

Method

Wald Test

Parameter type

Mean difference (final values)

Point estimate

-2.29

Confidence interval

level

60%

sides

2-sided

lower limit

-7.61

upper limit

3.02

Variability estimate

Standard error of the mean

Dispersion value

6.31

Notes
[125] - Point estimates, lower and upper confidence limits represent percentages. The mean difference and standard error of the mean is the percentage difference and standard error of the percentage difference.

Percentage of Participants with Combined BR

Statistical analysis description

Month 12

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[126]

P-value

= 0.4692

Method

Wald Test

Parameter type

Mean difference (final values)

Point estimate

-4.51

Confidence interval

level

60%

sides

2-sided

lower limit

-9.76

upper limit

0.73

Variability estimate

Standard error of the mean

Dispersion value

6.24

Notes
[126] - Point estimates, lower and upper confidence limits represent percentages. The mean difference and standard error of the mean is the percentage difference and standard error of the percentage difference.

Secondary: Kaplan-Meier Analysis of Percent of Participants with Graft Survival with Death Censored by Visit

Top of page

End point title

Kaplan-Meier Analysis of Percent of Participants with Graft Survival with Death Censored by Visit

End point description

Graft loss was defined as graft nephrectomy, subject death, retransplantation, or return to dialysis for at least 6 consecutive weeks. The 'Number' and 'Confidence Interval 60%' columns represent cumulative proportions and 60% CIs as estimated from the fitted Kaplan-Meier curves for each treatment at scheduled visits. Included data up to 2 months postdose in the clinical Follow-up visit.

End point type

Secondary

End point timeframe

Months 12, 15, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72

End point values	Cyclosporine (CsA)	Tofacitinib Less Intensive (LI)	Tofacitinib More Intensive (MI)
Number of subjects analysed	64	60	54
Units: Percentage of participants
number (confidence interval 60%)
Month 12 (n=64,60,54)	100 (99.58 to 100)	100 (98.48 to 100)	100 (98.32 to 100)
Month 15 (n=64,60,54)	100 (95.58 to 100)	100 (98.48 to 100)	100 (98.32 to 100)
Month 18 (n=62,59,51)	100 (98.53 to 100)	100 (98.46 to 100)	100 (98.22 to 100)
Month 24 (n=59,58,45)	100 (98.46 to 100)	100 (98.43 to 100)	100 (97.98 to 100)
Month 30 (n=55,42,31)	98.31 (96.89 to 99.72)	100 (97.84 to 100)	100 (97.09 to 100)
Month 36 (n=53,32,16)	96.48 (94.43 to 98.54)	100 (97.18 to 100)	100 (94.43 to 100)
Month 42 (n=46,32,15)	96.48 (94.43 to 98.54)	100 (97.18 to 100)	100 (94.07 to 100)
Month 48 (n=44,32,15)	96.48 (94.43 to 98.54)	100 (97.18 to 100)	100 (94.07 to 100)
Month 54 (n=43,31,14)	96.48 (94.43 to 98.54)	100 (97.09 to 100)	100 (93.66 to 100)
Month 60 (n=40,26,13)	96.48 (94.43 to 98.54)	100 (96.54 to 100)	100 (93.19 to 100)
Month 66 (n=35,23,11)	96.48 (94.43 to 98.54)	100 (96.09 to 100)	100 (92.01 to 100)
Month 72 (n=31,20,11)	96.48 (94.43 to 98.54)	100 (95.52 to 100)	100 (92.01 to 100)

Percent of Participants with Graft Survival

Statistical analysis description

Month 30

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[127]

P-value

= 0.3132

Method

Wald Test

Parameter type

Mean difference (final values)

Point estimate

1.69

Confidence interval

level

60%

sides

2-sided

lower limit

0.28

upper limit

3.11

Variability estimate

Standard error of the mean

Dispersion value

1.68

Notes
[127] - Point estimates, lower and upper confidence limits represent percentages. The mean difference and standard error of the mean is the percentage difference and standard error of the percentage difference.

Percent of Participants with Graft Survival

Statistical analysis description

Month 30

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[128]

P-value

= 0.3132

Method

Wald Test

Parameter type

Mean difference (final values)

Point estimate

1.69

Confidence interval

level

60%

sides

2-sided

lower limit

0.28

upper limit

3.11

Variability estimate

Standard error of the mean

Dispersion value

1.68

Notes
[128] - Point estimates, lower and upper confidence limits represent percentages. The mean difference and standard error of the mean is the percentage difference and standard error of the percentage difference.

Percent of Participants with Graft Survival

Statistical analysis description

Month 36

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[129]

P-value

= 0.1503

Method

Wald Test

Parameter type

Mean difference (final values)

Point estimate

3.52

Confidence interval

level

60%

sides

2-sided

lower limit

1.46

upper limit

5.57

Variability estimate

Standard error of the mean

Dispersion value

2.44

Notes
[129] - Point estimates, lower and upper confidence limits represent percentages. The mean difference and standard error of the mean is the percentage difference and standard error of the percentage difference.

Percent of Participants with Graft Survival

Statistical analysis description

Month 36

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[130]

P-value

= 0.1503

Method

Wald Test

Parameter type

Mean difference (final values)

Point estimate

3.52

Confidence interval

level

60%

sides

2-sided

lower limit

1.46

upper limit

5.57

Variability estimate

Standard error of the mean

Dispersion value

2.44

Notes
[130] - Point estimates, lower and upper confidence limits represent percentages. The mean difference and standard error of the mean is the percentage difference and standard error of the percentage difference.

Percent of Participants with Graft Survival

Statistical analysis description

Month 42

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[131]

P-value

= 0.1503

Method

Wald Test

Parameter type

Mean difference (final values)

Point estimate

3.52

Confidence interval

level

60%

sides

2-sided

lower limit

1.46

upper limit

5.57

Variability estimate

Standard error of the mean

Dispersion value

2.44

Notes
[131] - Point estimates, lower and upper confidence limits represent percentages. The mean difference and standard error of the mean is the percentage difference and standard error of the percentage difference.

Percent of Participants with Graft Survival

Statistical analysis description

Month 42

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[132]

P-value

= 0.1503

Method

Wald Test

Parameter type

Mean difference (final values)

Point estimate

3.52

Confidence interval

level

60%

sides

2-sided

lower limit

1.46

upper limit

5.57

Variability estimate

Standard error of the mean

Dispersion value

2.44

Notes
[132] - Point estimates, lower and upper confidence limits represent percentages. The mean difference and standard error of the mean is the percentage difference and standard error of the percentage difference.

Percent of Participants with Graft Survival

Statistical analysis description

Month 48

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[133]

P-value

= 0.1503

Method

Wald Test

Parameter type

Mean difference (final values)

Point estimate

3.52

Confidence interval

level

60%

sides

2-sided

lower limit

1.46

upper limit

5.57

Variability estimate

Standard error of the mean

Dispersion value

2.44

Notes
[133] - Point estimates, lower and upper confidence limits represent percentages. The mean difference and standard error of the mean is the percentage difference and standard error of the percentage difference.

Percent of Participants with Graft Survival

Statistical analysis description

Month 48

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[134]

P-value

= 0.1503

Method

Wald Test

Parameter type

Mean difference (final values)

Point estimate

3.52

Confidence interval

level

60%

sides

2-sided

lower limit

1.46

upper limit

5.57

Variability estimate

Standard error of the mean

Dispersion value

2.44

Notes
[134] - Point estimates, lower and upper confidence limits represent percentages. The mean difference and standard error of the mean is the percentage difference and standard error of the percentage difference.

Percent of Participants with Graft Survival

Statistical analysis description

Month 54

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[135]

P-value

= 0.1503

Method

Wald Test

Parameter type

Mean difference (final values)

Point estimate

3.52

Confidence interval

level

60%

sides

2-sided

lower limit

1.46

upper limit

5.57

Variability estimate

Standard error of the mean

Dispersion value

2.44

Notes
[135] - Point estimates, lower and upper confidence limits represent percentages. The mean difference and standard error of the mean is the percentage difference and standard error of the percentage difference.

Percent of Participants with Graft Survival

Statistical analysis description

Month 54

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[136]

P-value

= 0.1503

Method

Wald Test

Parameter type

Mean difference (final values)

Point estimate

3.52

Confidence interval

level

60%

sides

2-sided

lower limit

1.46

upper limit

5.57

Variability estimate

Standard error of the mean

Dispersion value

2.44

Notes
[136] - Point estimates, lower and upper confidence limits represent percentages. The mean difference and standard error of the mean is the percentage difference and standard error of the percentage difference.

Percent of Participants with Graft Survival

Statistical analysis description

Month 60

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[137]

P-value

= 0.1503

Method

Wald Test

Parameter type

Mean difference (final values)

Point estimate

3.52

Confidence interval

level

60%

sides

2-sided

lower limit

1.46

upper limit

5.57

Variability estimate

Standard error of the mean

Dispersion value

2.44

Notes
[137] - Point estimates, lower and upper confidence limits represent percentages. The mean difference and standard error of the mean is the percentage difference and standard error of the percentage difference.

Percent of Participants with Graft Survival

Statistical analysis description

Month 60

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[138]

P-value

= 0.1503

Method

Wald Test

Parameter type

Mean difference (final values)

Point estimate

3.52

Confidence interval

level

60%

sides

2-sided

lower limit

1.46

upper limit

5.57

Variability estimate

Standard error of the mean

Dispersion value

2.44

Notes
[138] - Point estimates, lower and upper confidence limits represent percentages. The mean difference and standard error of the mean is the percentage difference and standard error of the percentage difference.

Percent of Participants with Graft Survival

Statistical analysis description

Month 66

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[139]

P-value

= 0.1503

Method

Wald Test

Parameter type

Mean difference (final values)

Point estimate

3.52

Confidence interval

level

60%

sides

2-sided

lower limit

1.46

upper limit

5.57

Variability estimate

Standard error of the mean

Dispersion value

2.44

Notes
[139] - Point estimates, lower and upper confidence limits represent percentages. The mean difference and standard error of the mean is the percentage difference and standard error of the percentage difference.

Percent of Participants with Graft Survival

Statistical analysis description

Month 66

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[140]

P-value

= 0.1503

Method

Wald Test

Parameter type

Mean difference (final values)

Point estimate

3.52

Confidence interval

level

60%

sides

2-sided

lower limit

1.46

upper limit

5.57

Variability estimate

Standard error of the mean

Dispersion value

2.44

Notes
[140] - Point estimates, lower and upper confidence limits represent percentages. The mean difference and standard error of the mean is the percentage difference and standard error of the percentage difference.

Percent of Participants with Graft Survival

Statistical analysis description

Month 72

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[141]

P-value

= 0.1503

Method

Wald Test

Parameter type

Mean difference (final values)

Point estimate

3.52

Confidence interval

level

60%

sides

2-sided

lower limit

1.46

upper limit

5.57

Variability estimate

Standard error of the mean

Dispersion value

2.44

Notes
[141] - Point estimates, lower and upper confidence limits represent percentages. The mean difference and standard error of the mean is the percentage difference and standard error of the percentage difference.

Percent of Participants with Graft Survival

Statistical analysis description

Month 72

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[142]

P-value

= 0.1503

Method

Wald Test

Parameter type

Mean difference (final values)

Point estimate

3.52

Confidence interval

level

60%

sides

2-sided

lower limit

1.46

upper limit

5.57

Variability estimate

Standard error of the mean

Dispersion value

2.44

Notes
[142] - Point estimates, lower and upper confidence limits represent percentages. The mean difference and standard error of the mean is the percentage difference and standard error of the percentage difference.

Secondary: Kaplan-Meier Analysis of Percentage of Participants Surviving by Visit

Top of page

End point title

Kaplan-Meier Analysis of Percentage of Participants Surviving by Visit

End point description

The 'Number' and 'Confidence Interval 60%' columns represent cumulative proportions and 60% CIs as estimated from the fitted Kaplan-Meier curves for each treatment at scheduled visits. Included data up to 2 months postdose in the clinical Follow-up visit.

End point type

Secondary

End point timeframe

Months 12, 15, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72

End point values	Cyclosporine (CsA)	Tofacitinib Less Intensive (LI)	Tofacitinib More Intensive (MI)
Number of subjects analysed	64	60	54
Units: Percentage of Participants
number (confidence interval 60%)
Month 12 (n=64,60,54)	100 (98.58 to 100)	100 (98.48 to 100)	100 (98.32 to 100)
Month 15 (n=64,60,53)	100 (98.58 to 100)	100 (98.48 to 100)	98.15 (96.6 to 99.69)
Month 18 (n=61,59,51)	98.41 (97.09 to 99.74)	100 (98.46 to 100)	98.15 (96.6 to 99.69)
Month 24 (n=59,58,44)	98.41 (97.09 to 99.74)	100 (98.43 to 100)	94.22 (91.49 to 96.95)
Month 30 (n=55,42,31)	98.41 (97.09 to 99.74)	100 (97.84 to 100)	94.22 (91.49 to 96.95)
Month 36 (n=53,32,16)	98.41 (97.09 to 99.74)	100 (97.18 to 100)	90.97 (87.21 to 94.73)
Month 42 (n=45,32,15)	96.27 (94.07 to 98.48)	100 (97.18 to 100)	90.97 (87.21 to 94.73)
Month 48 (n=44,32,15)	96.27 (94.07 to 98.48)	100 (97.18 to 100)	90.97 (87.21 to 94.73)
Month 54 (n=43,31,14)	94.09 (91.27 to 96.9)	100 (97.09 to 100)	90.97 (87.21 to 94.73)
Month 60 (n=40,26,13)	94.09 (91.27 to 96.9)	100 (96.54 to 100)	90.97 (87.21 to 94.73)
Month 66 (n=35,23,11)	94.09 (91.27 to 96.9)	100 (96.09 to 100)	90.97 (87.21 to 94.73)
Month 72 (n=31,20,11)	94.09 (91.27 to 96.9)	100 (95.52 to 100)	90.97 (87.21 to 94.73)

Percentage of Participants Surviving by Visit

Statistical analysis description

Month 15

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[143]

P-value

= 0.3128

Method

Wald Test

Parameter type

Mean difference (final values)

Point estimate

-1.85

Confidence interval

level

60%

sides

2-sided

lower limit

-3.4

upper limit

-0.31

Variability estimate

Standard error of the mean

Dispersion value

1.83

Notes
[143] - Point estimates, lower and upper confidence limits represent percentages. The mean difference and standard error of the mean is the percentage difference and standard error of the percentage difference.

Percentage of Participants Surviving by Visit

Statistical analysis description

Month 18

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[144]

P-value

= 0.3134

Method

Wald Test

Parameter type

Mean difference (final values)

Point estimate

1.59

Confidence interval

level

60%

sides

2-sided

lower limit

0.26

upper limit

2.91

Variability estimate

Standard error of the mean

Dispersion value

1.57

Notes
[144] - Point estimates, lower and upper confidence limits represent percentages. The mean difference and standard error of the mean is the percentage difference and standard error of the percentage difference.

Percentage of Participants Surviving by Visit

Statistical analysis description

Month 18

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[145]

P-value

= 0.9129

Method

Wald Test

Parameter type

Mean difference (final values)

Point estimate

-0.26

Confidence interval

level

60%

sides

2-sided

lower limit

-2.3

upper limit

1.77

Variability estimate

Standard error of the mean

Dispersion value

2.42

Notes
[145] - Point estimates, lower and upper confidence limits represent percentages. The mean difference and standard error of the mean is the percentage difference and standard error of the percentage difference.

Percentage of Participants Surviving by Visit

Statistical analysis description

Month 24

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[146]

P-value

= 0.3134

Method

Wald Test

Parameter type

Mean difference (final values)

Point estimate

1.59

Confidence interval

level

60%

sides

2-sided

lower limit

0.26

upper limit

2.91

Variability estimate

Standard error of the mean

Dispersion value

1.57

Notes
[146] - Point estimates, lower and upper confidence limits represent percentages. The mean difference and standard error of the mean is the percentage difference and standard error of the percentage difference.

Percentage of Participants Surviving by Visit

Statistical analysis description

Month 24

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[147]

P-value

= 0.2447

Method

Wald Test

Parameter type

Mean difference (final values)

Point estimate

-4.19

Confidence interval

level

60%

sides

2-sided

lower limit

-7.23

upper limit

-1.16

Variability estimate

Standard error of the mean

Dispersion value

3.61

Notes
[147] - Point estimates, lower and upper confidence limits represent percentages. The mean difference and standard error of the mean is the percentage difference and standard error of the percentage difference.

Percentage of Participants Surviving by Visit

Statistical analysis description

Month 30

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[148]

P-value

= 0.3134

Method

Wald Test

Parameter type

Mean difference (final values)

Point estimate

1.59

Confidence interval

level

60%

sides

2-sided

lower limit

0.26

upper limit

2.91

Variability estimate

Standard error of the mean

Dispersion value

1.57

Notes
[148] - Point estimates, lower and upper confidence limits represent percentages. The mean difference and standard error of the mean is the percentage difference and standard error of the percentage difference.

Percentage of Participants Surviving by Visit

Statistical analysis description

Month 30

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[149]

P-value

= 0.2447

Method

Wald Test

Parameter type

Mean difference (final values)

Point estimate

-4.19

Confidence interval

level

60%

sides

2-sided

lower limit

-7.23

upper limit

-1.16

Variability estimate

Standard error of the mean

Dispersion value

3.61

Notes
[149] - Point estimates, lower and upper confidence limits represent percentages. The mean difference and standard error of the mean is the percentage difference and standard error of the percentage difference.

Percentage of Participants Surviving by Visit

Statistical analysis description

Month 36

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[150]

P-value

= 0.3134

Method

Wald Test

Parameter type

Mean difference (final values)

Point estimate

1.59

Confidence interval

level

60%

sides

2-sided

lower limit

0.26

upper limit

2.91

Variability estimate

Standard error of the mean

Dispersion value

1.57

Notes
[150] - Point estimates, lower and upper confidence limits represent percentages. The mean difference and standard error of the mean is the percentage difference and standard error of the percentage difference.

Percentage of Participants Surviving by Visit

Statistical analysis description

Month 36

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[151]

P-value

= 0.1164

Method

Wald Test

Parameter type

Mean difference (final values)

Point estimate

-7.44

Confidence interval

level

60%

sides

2-sided

lower limit

-11.43

upper limit

-3.45

Variability estimate

Standard error of the mean

Dispersion value

4.74

Notes
[151] - Point estimates, lower and upper confidence limits represent percentages. The mean difference and standard error of the mean is the percentage difference and standard error of the percentage difference.

Percentage of Participants Surviving by Visit

Statistical analysis description

Month 42

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[152]

P-value

= 0.1545

Method

Wald Test

Parameter type

Mean difference (final values)

Point estimate

3.73

Confidence interval

level

60%

sides

2-sided

lower limit

1.52

upper limit

5.93

Variability estimate

Standard error of the mean

Dispersion value

2.62

Notes
[152] - Point estimates, lower and upper confidence limits represent percentages. The mean difference and standard error of the mean is the percentage difference and standard error of the percentage difference.

Percentage of Participants Surviving by Visit

Statistical analysis description

Month 42

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[153]

P-value

= 0.3061

Method

Wald Test

Parameter type

Mean difference (final values)

Point estimate

-5.3

Confidence interval

level

60%

sides

2-sided

lower limit

-9.66

upper limit

-0.94

Variability estimate

Standard error of the mean

Dispersion value

5.18

Notes
[153] - Point estimates, lower and upper confidence limits represent percentages. The mean difference and standard error of the mean is the percentage difference and standard error of the percentage difference.

Percentage of Participants Surviving by Visit

Statistical analysis description

Month 48

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[154]

P-value

= 0.1545

Method

Wald Test

Parameter type

Mean difference (final values)

Point estimate

3.73

Confidence interval

level

60%

sides

2-sided

lower limit

1.52

upper limit

5.93

Variability estimate

Standard error of the mean

Dispersion value

2.62

Notes
[154] - Point estimates, lower and upper confidence limits represent percentages. The mean difference and standard error of the mean is the percentage difference and standard error of the percentage difference.

Percentage of Participants Surviving by Visit

Statistical analysis description

Month 48

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[155]

P-value

= 0.3061

Method

Wald Test

Parameter type

Mean difference (final values)

Point estimate

-5.3

Confidence interval

level

60%

sides

2-sided

lower limit

-9.66

upper limit

-0.94

Variability estimate

Standard error of the mean

Dispersion value

5.18

Notes
[155] - Point estimates, lower and upper confidence limits represent percentages. The mean difference and standard error of the mean is the percentage difference and standard error of the percentage difference.

Percentage of Participants Surviving by Visit

Statistical analysis description

Month 54

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[156]

P-value

= 0.0774

Method

Wald Test

Parameter type

Mean difference (final values)

Point estimate

5.91

Confidence interval

level

60%

sides

2-sided

lower limit

3.1

upper limit

8.73

Variability estimate

Standard error of the mean

Dispersion value

3.35

Notes
[156] - Point estimates, lower and upper confidence limits represent percentages. The mean difference and standard error of the mean is the percentage difference and standard error of the percentage difference.

Percentage of Participants Surviving by Visit

Statistical analysis description

Month 54

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[157]

P-value

= 0.5772

Method

Wald Test

Parameter type

Mean difference (final values)

Point estimate

-3.12

Confidence interval

level

60%

sides

2-sided

lower limit

-7.82

upper limit

1.59

Variability estimate

Standard error of the mean

Dispersion value

5.59

Notes
[157] - Point estimates, lower and upper confidence limits represent percentages. The mean difference and standard error of the mean is the percentage difference and standard error of the percentage difference.

Percentage of Participants Surviving by Visit

Statistical analysis description

Month 60

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[158]

P-value

= 0.0774

Method

Wald Test

Parameter type

Mean difference (final values)

Point estimate

5.91

Confidence interval

level

60%

sides

2-sided

lower limit

3.1

upper limit

8.73

Variability estimate

Standard error of the mean

Dispersion value

3.35

Notes
[158] - Point estimates, lower and upper confidence limits represent percentages. The mean difference and standard error of the mean is the percentage difference and standard error of the percentage difference.

Percentage of Participants Surviving by Visit

Statistical analysis description

Month 60

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[159]

P-value

= 0.5772

Method

Wald Test

Parameter type

Mean difference (final values)

Point estimate

-3.12

Confidence interval

level

60%

sides

2-sided

lower limit

-7.82

upper limit

1.59

Variability estimate

Standard error of the mean

Dispersion value

5.59

Notes
[159] - Point estimates, lower and upper confidence limits represent percentages. The mean difference and standard error of the mean is the percentage difference and standard error of the percentage difference.

Percentage of Participants Surviving by Visit

Statistical analysis description

Month 66

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[160]

P-value

= 0.0774

Method

Wald Test

Parameter type

Mean difference (final values)

Point estimate

5.91

Confidence interval

level

60%

sides

2-sided

lower limit

3.1

upper limit

8.73

Variability estimate

Standard error of the mean

Dispersion value

3.35

Notes
[160] - Point estimates, lower and upper confidence limits represent percentages. The mean difference and standard error of the mean is the percentage difference and standard error of the percentage difference.

Percentage of Participants Surviving by Visit

Statistical analysis description

Month 66

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[161]

P-value

= 0.5772

Method

Wald Test

Parameter type

Mean difference (final values)

Point estimate

-3.12

Confidence interval

level

60%

sides

2-sided

lower limit

-7.82

upper limit

1.59

Variability estimate

Standard error of the mean

Dispersion value

5.59

Notes
[161] - Point estimates, lower and upper confidence limits represent percentages. The mean difference and standard error of the mean is the percentage difference and standard error of the percentage difference.

Percentage of Participants Surviving by Visit

Statistical analysis description

Month 72

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[162]

P-value

= 0.0774

Method

Wald Test

Parameter type

Mean difference (final values)

Point estimate

5.91

Confidence interval

level

60%

sides

2-sided

lower limit

3.1

upper limit

8.73

Variability estimate

Standard error of the mean

Dispersion value

3.35

Notes
[162] - Point estimates, lower and upper confidence limits represent percentages. The mean difference and standard error of the mean is the percentage difference and standard error of the percentage difference.

Percentage of Participants Surviving by Visit

Statistical analysis description

Month 72

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[163]

P-value

= 0.5772

Method

Wald Test

Parameter type

Mean difference (final values)

Point estimate

-3.12

Confidence interval

level

60%

sides

2-sided

lower limit

-7.82

upper limit

1.59

Variability estimate

Standard error of the mean

Dispersion value

5.59

Notes
[163] - Point estimates, lower and upper confidence limits represent percentages. The mean difference and standard error of the mean is the percentage difference and standard error of the percentage difference.

Secondary: Percentage of Participants Discontinuing from the Study

Top of page

End point title

Percentage of Participants Discontinuing from the Study

End point description

Discontinuations were due to any reason including those occurring as a result of protocol Amendments 3 and 4.

End point type

Secondary

End point timeframe

Months 12 through 72.

End point values	Cyclosporine (CsA)	Tofacitinib Less Intensive (LI)	Tofacitinib More Intensive (MI)
Number of subjects analysed	64	60	54
Units: Percentage of Participants
number (not applicable)	43.8	75	85.2

No statistical analyses for this end point

Secondary: Least Squares (LS) Means of Total Serum Cholesterol Levels (milligrams per deciliter [mg/dL]) by Visit

Top of page

End point title

Least Squares (LS) Means of Total Serum Cholesterol Levels (milligrams per deciliter [mg/dL]) by Visit

End point description

Model contained treatment, visit and treatment by visit interaction as fixed effects and Baseline (predose in Study A3921030) as a covariate. A first-order autoregressive variance-covariance structure was used.

End point type

Secondary

End point timeframe

Months 15, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72

End point values	Cyclosporine (CsA)	Tofacitinib Less Intensive (LI)	Tofacitinib More Intensive (MI)
Number of subjects analysed	64	60	54
Units: mg/dL
least squares mean (standard error)
Month 15 (n=59,59,49)	199.14 ( 5.71 )	213.49 ( 5.81 )	196.27 ( 6.29 )
Month 18 (n=59,59,49)	200.51 ( 5.75 )	212.67 ( 5.82 )	193.5 ( 6.34 )
Month 24 (n=58,54,40)	198.78 ( 5.82 )	212.3 ( 5.98 )	185.57 ( 6.8 )
Month 30 (n=52,37,26)	193.99 ( 6.05 )	211.59 ( 6.84 )	202.73 ( 8.08 )
Month 36 (n=51,32,15)	198.62 ( 6.17 )	211.14 ( 7.51 )	192.97 ( 10.37 )
Month 42 (n=44,31,15)	200.36 ( 6.52 )	220.29 ( 7.83 )	208.77 ( 11.13 )
Month 48 (n=42,30,14)	196.56 ( 6.74 )	228.83 ( 7.98 )	188.83 ( 11.66 )
Month 54 (n=41,31,13)	193.66 ( 6.87 )	222.86 ( 7.98 )	183.17 ( 12.06 )
Month 60 (n=37,23,12)	190.1 ( 7.17 )	220.47 ( 8.85 )	184.14 ( 12.53 )
Month 66 (n=34,20,11)	191 ( 7.47 )	218.77 ( 9.47 )	189.15 ( 13.14 )
Month 72 (n=31,17,11)	188.74 ( 7.82 )	209.12 ( 10.26 )	182.6 ( 13.36 )

LS Means of Total Serum Cholesterol Levels

Statistical analysis description

Month 15

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[164]

P-value

= 0.0786

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

14.35

Confidence interval

level

60%

sides

2-sided

lower limit

7.49

upper limit

21.22

Variability estimate

Standard error of the mean

Dispersion value

8.15

Notes
[164] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of Total Serum Cholesterol Levels

Statistical analysis description

Month 15

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[165]

P-value

= 0.736

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-2.87

Confidence interval

level

60%

sides

2-sided

lower limit

-10.03

upper limit

4.29

Variability estimate

Standard error of the mean

Dispersion value

8.5

Notes
[165] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of Total Serum Cholesterol Levels

Statistical analysis description

Month 18

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[166]

P-value

= 0.1377

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

12.16

Confidence interval

level

60%

sides

2-sided

lower limit

5.27

upper limit

19.05

Variability estimate

Standard error of the mean

Dispersion value

8.19

Notes
[166] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of Total Serum Cholesterol Levels

Statistical analysis description

Month 18

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[167]

P-value

= 0.4131

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-7.01

Confidence interval

level

60%

sides

2-sided

lower limit

-14.21

upper limit

0.2

Variability estimate

Standard error of the mean

Dispersion value

8.56

Notes
[167] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of Total Serum Cholesterol Levels

Statistical analysis description

Month 24

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[168]

P-value

= 0.1057

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

13.52

Confidence interval

level

60%

sides

2-sided

lower limit

6.49

upper limit

20.55

Variability estimate

Standard error of the mean

Dispersion value

8.35

Notes
[168] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of Total Serum Cholesterol Levels

Statistical analysis description

Month 24

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[169]

P-value

= 0.1402

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-13.21

Confidence interval

level

60%

sides

2-sided

lower limit

-20.75

upper limit

-5.68

Variability estimate

Standard error of the mean

Dispersion value

8.95

Notes
[169] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of Total Serum Cholesterol Levels

Statistical analysis description

Month 30

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[170]

P-value

= 0.0542

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

17.6

Confidence interval

level

60%

sides

2-sided

lower limit

9.91

upper limit

25.29

Variability estimate

Standard error of the mean

Dispersion value

9.13

Notes
[170] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of Total Serum Cholesterol Levels

Statistical analysis description

Month 30

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[171]

P-value

= 0.3866

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

8.74

Confidence interval

level

60%

sides

2-sided

lower limit

0.24

upper limit

17.24

Variability estimate

Standard error of the mean

Dispersion value

10.09

Notes
[171] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of Total Serum Cholesterol Levels

Statistical analysis description

Month 36

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[172]

P-value

= 0.1981

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

12.52

Confidence interval

level

60%

sides

2-sided

lower limit

4.33

upper limit

20.71

Variability estimate

Standard error of the mean

Dispersion value

9.72

Notes
[172] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of Total Serum Cholesterol Levels

Statistical analysis description

Month 36

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[173]

P-value

= 0.6397

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-5.65

Confidence interval

level

60%

sides

2-sided

lower limit

-15.81

upper limit

4.51

Variability estimate

Standard error of the mean

Dispersion value

12.07

Notes
[173] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of Total Serum Cholesterol Levels

Statistical analysis description

Month 42

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[174]

P-value

= 0.0508

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

19.93

Confidence interval

level

60%

sides

2-sided

lower limit

11.35

upper limit

28.51

Variability estimate

Standard error of the mean

Dispersion value

10.19

Notes
[174] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of Total Serum Cholesterol Levels

Statistical analysis description

Month 42

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[175]

P-value

= 0.5143

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

8.42

Confidence interval

level

60%

sides

2-sided

lower limit

-2.45

upper limit

19.28

Variability estimate

Standard error of the mean

Dispersion value

12.9

Notes
[175] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of Total Serum Cholesterol Levels

Statistical analysis description

Month 48

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[176]

P-value

= 0.0021

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

32.26

Confidence interval

level

60%

sides

2-sided

lower limit

23.46

upper limit

41.06

Variability estimate

Standard error of the mean

Dispersion value

10.45

Notes
[176] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS means of Total Serum Cholesterol Levels

Statistical analysis description

Month 48

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[177]

P-value

= 0.5661

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-7.73

Confidence interval

level

60%

sides

2-sided

lower limit

-19.07

upper limit

3.61

Variability estimate

Standard error of the mean

Dispersion value

13.47

Notes
[177] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of Total Serum Cholesterol Levels

Statistical analysis description

Month 54

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[178]

P-value

= 0.0057

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

29.2

Confidence interval

level

60%

sides

2-sided

lower limit

20.33

upper limit

38.08

Variability estimate

Standard error of the mean

Dispersion value

10.54

Notes
[178] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of Total Serum Cholesterol Levels

Statistical analysis description

Month 54

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[179]

P-value

= 0.4504

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-10.49

Confidence interval

level

60%

sides

2-sided

lower limit

-22.18

upper limit

1.21

Variability estimate

Standard error of the mean

Dispersion value

13.89

Notes
[179] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of Total Serum Cholesterol Levels

Statistical analysis description

Month 60

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[180]

P-value

= 0.0078

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

30.37

Confidence interval

level

60%

sides

2-sided

lower limit

20.78

upper limit

39.96

Variability estimate

Standard error of the mean

Dispersion value

11.39

Notes
[180] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of Total Serum Cholesterol Levels

Statistical analysis description

Month 60

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[181]

P-value

= 0.6802

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-5.95

Confidence interval

level

60%

sides

2-sided

lower limit

-18.11

upper limit

6.2

Variability estimate

Standard error of the mean

Dispersion value

14.44

Notes
[181] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of Total Serum Cholesterol Levels

Statistical analysis description

Month 66

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[182]

P-value

= 0.0216

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

27.78

Confidence interval

level

60%

sides

2-sided

lower limit

17.61

upper limit

37.95

Variability estimate

Standard error of the mean

Dispersion value

12.08

Notes
[182] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of Total Serum Cholesterol Levels

Statistical analysis description

Month 66

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[183]

P-value

= 0.9026

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-1.85

Confidence interval

level

60%

sides

2-sided

lower limit

-14.58

upper limit

10.88

Variability estimate

Standard error of the mean

Dispersion value

15.12

Notes
[183] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of Total Serum Cholesterol Levels

Statistical analysis description

Month 72

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[184]

P-value

= 0.1146

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

20.38

Confidence interval

level

60%

sides

2-sided

lower limit

9.51

upper limit

31.24

Variability estimate

Standard error of the mean

Dispersion value

12.91

Notes
[184] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of Total Serum Cholesterol Levels

Statistical analysis description

Month 72

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[185]

P-value

= 0.6918

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-6.14

Confidence interval

level

60%

sides

2-sided

lower limit

-19.18

upper limit

6.9

Variability estimate

Standard error of the mean

Dispersion value

15.48

Notes
[185] - 'Standard error of the mean' refers to 'standard error of the mean difference'

Secondary: LS Means of Total Serum Low Density Lipoprotein (LDL) Cholesterol Levels (mg/dL) by Visit

Top of page

End point title

LS Means of Total Serum Low Density Lipoprotein (LDL) Cholesterol Levels (mg/dL) by Visit

End point description

End point type

Secondary

End point timeframe

Months 15, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72

End point values	Cyclosporine (CsA)	Tofacitinib Less Intensive (LI)	Tofacitinib More Intensive (MI)
Number of subjects analysed	64	60	54
Units: mg/dL
least squares mean (standard error)
Month 15 (n=54,54,48)	113.09 ( 4.6 )	119.71 ( 4.68 )	108.72 ( 4.94 )
Month 18 (n=56,54,49)	112.82 ( 4.58 )	119.36 ( 4.69 )	109.87 ( 4.94 )
Month 24 (n=55,49,40)	111.14 ( 4.64 )	119.15 ( 4.83 )	104.63 ( 5.29 )
Month 30 (n=49,36,25)	106.79 ( 4.84 )	125.24 ( 5.43 )	112.44 ( 6.36 )
Month 36 (n=47,31,15)	112.81 ( 4.97 )	123.27 ( 5.95 )	109.54 ( 8.1 )
Month 42 (n=42,27,15)	110.98 ( 5.21 )	122.51 ( 6.39 )	121.74 ( 8.67 )
Month 48 (n=41,27,14)	109.03 ( 5.35 )	127.65 ( 6.48 )	105.59 ( 9.08 )
Month 54 (n=40,28,13)	107.21 ( 5.44 )	128.39 ( 6.45 )	96.6 ( 9.39 )
Month 60 (n=36,21,12)	105.37 ( 5.66 )	123.71 ( 7.18 )	97.79 ( 9.75 )
Month 66 (n=32,19,11)	104.31 ( 5.95 )	123.74 ( 7.64 )	102.44 ( 10.23 )
Month 72 (n=30,16,11)	109.18 ( 6.19 )	116.17 ( 8.27 )	96.11 ( 10.4 )

LS Means of Total Serum LDL Cholesterol Levels

Statistical analysis description

Month 15

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[186]

P-value

= 0.3139

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

6.62

Confidence interval

level

60%

sides

2-sided

lower limit

1.09

upper limit

12.14

Variability estimate

Standard error of the mean

Dispersion value

6.57

Notes
[186] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of Total Serum LDL Cholesterol Levels

Statistical analysis description

Month 15

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[187]

P-value

= 0.5176

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-4.37

Confidence interval

level

60%

sides

2-sided

lower limit

-10.06

upper limit

1.31

Variability estimate

Standard error of the mean

Dispersion value

6.75

Notes
[187] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of Total Serum LDL Cholesterol Levels

Statistical analysis description

Month 18

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[188]

P-value

= 0.3191

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

6.54

Confidence interval

level

60%

sides

2-sided

lower limit

1.02

upper limit

12.06

Variability estimate

Standard error of the mean

Dispersion value

6.56

Notes
[188] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of Total Serum LDL Cholesterol Levels

Statistical analysis description

Month 18

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[189]

P-value

= 0.6608

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-2.95

Confidence interval

level

60%

sides

2-sided

lower limit

-8.62

upper limit

2.71

Variability estimate

Standard error of the mean

Dispersion value

6.73

Notes
[189] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of Total Serum LDL Cholesterol Levels

Statistical analysis description

Month 24

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[190]

P-value

= 0.2319

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

8.02

Confidence interval

level

60%

sides

2-sided

lower limit

2.37

upper limit

13.66

Variability estimate

Standard error of the mean

Dispersion value

6.7

Notes
[190] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of Total Serum LDL Cholesterol Levels

Statistical analysis description

Month 24

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[191]

P-value

= 0.3554

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-6.5

Confidence interval

level

60%

sides

2-sided

lower limit

-12.43

upper limit

-0.58

Variability estimate

Standard error of the mean

Dispersion value

7.04

Notes
[191] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of Total Serum LDL Cholesterol Levels

Statistical analysis description

Month 30

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[192]

P-value

= 0.0113

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

18.45

Confidence interval

level

60%

sides

2-sided

lower limit

12.33

upper limit

24.57

Variability estimate

Standard error of the mean

Dispersion value

7.27

Notes
[192] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of Total Serum LDL Cholesterol Levels

Statistical analysis description

Month 30

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[193]

P-value

= 0.479

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

5.66

Confidence interval

level

60%

sides

2-sided

lower limit

-1.07

upper limit

12.39

Variability estimate

Standard error of the mean

Dispersion value

7.99

Notes
[193] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of Total Serum LDL Cholesterol Levels

Statistical analysis description

Month 36

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[194]

P-value

= 0.1776

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

10.46

Confidence interval

level

60%

sides

2-sided

lower limit

3.93

upper limit

16.99

Variability estimate

Standard error of the mean

Dispersion value

7.75

Notes
[194] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of Total Serum LDL Cholesterol Levels

Statistical analysis description

Month 36

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[195]

P-value

= 0.7307

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-3.27

Confidence interval

level

60%

sides

2-sided

lower limit

-11.27

upper limit

4.73

Variability estimate

Standard error of the mean

Dispersion value

9.5

Notes
[195] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS means of Total Serum LDL Cholesterol Levels

Statistical analysis description

Month 42

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[196]

P-value

= 0.1625

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

11.53

Confidence interval

level

60%

sides

2-sided

lower limit

4.59

upper limit

18.48

Variability estimate

Standard error of the mean

Dispersion value

8.25

Notes
[196] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of Total Serum LDL Cholesterol Levels

Statistical analysis description

Month 42

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[197]

P-value

= 0.2876

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

10.77

Confidence interval

level

60%

sides

2-sided

lower limit

2.25

upper limit

19.29

Variability estimate

Standard error of the mean

Dispersion value

10.12

Notes
[197] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of Total Serum LDL Cholesterol Levels

Statistical analysis description

Month 48

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[198]

P-value

= 0.027

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

18.62

Confidence interval

level

60%

sides

2-sided

lower limit

11.54

upper limit

25.7

Variability estimate

Standard error of the mean

Dispersion value

8.41

Notes
[198] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of Total Serum LDL Cholesterol Levels

Statistical analysis description

Month 48

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[199]

P-value

= 0.7444

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-3.44

Confidence interval

level

60%

sides

2-sided

lower limit

-12.31

upper limit

5.44

Variability estimate

Standard error of the mean

Dispersion value

10.54

Notes
[199] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of Total Serum LDL Cholesterol Levels

Statistical analysis description

Month 54

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[200]

P-value

= 0.0122

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

21.18

Confidence interval

level

60%

sides

2-sided

lower limit

14.08

upper limit

28.29

Variability estimate

Standard error of the mean

Dispersion value

8.44

Notes
[200] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of Total Serum LDL Cholesterol Levels

Statistical analysis description

Month 54

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[201]

P-value

= 0.3288

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-10.61

Confidence interval

level

60%

sides

2-sided

lower limit

-19.75

upper limit

-1.47

Variability estimate

Standard error of the mean

Dispersion value

10.86

Notes
[201] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of Total Serum LDL Cholesterol Levels

Statistical analysis description

Month 60

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[202]

P-value

= 0.0453

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

18.34

Confidence interval

level

60%

sides

2-sided

lower limit

10.63

upper limit

26.05

Variability estimate

Standard error of the mean

Dispersion value

9.15

Notes
[202] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of Total Serum LDL Cholesterol Levels

Statistical analysis description

Month 60

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[203]

P-value

= 0.5016

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-7.59

Confidence interval

level

60%

sides

2-sided

lower limit

-17.09

upper limit

1.91

Variability estimate

Standard error of the mean

Dispersion value

11.28

Notes
[203] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of Total Serum LDL Cholesterol Levels

Statistical analysis description

Month 66

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[204]

P-value

= 0.0453

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

19.43

Confidence interval

level

60%

sides

2-sided

lower limit

11.27

upper limit

27.59

Variability estimate

Standard error of the mean

Dispersion value

9.69

Notes
[204] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of Total Serum LDL Cholsterol Levels

Statistical analysis description

Month 66

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[205]

P-value

= 0.8747

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-1.87

Confidence interval

level

60%

sides

2-sided

lower limit

-11.83

upper limit

8.1

Variability estimate

Standard error of the mean

Dispersion value

11.84

Notes
[205] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of Total Serum LDL Cholesterol Levels

Statistical analysis description

Month 72

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[206]

P-value

= 0.4997

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

6.98

Confidence interval

level

60%

sides

2-sided

lower limit

-1.72

upper limit

15.69

Variability estimate

Standard error of the mean

Dispersion value

10.34

Notes
[206] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of Total Serum LDL Cholesterol Levels

Statistical analysis description

Month 72

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[207]

P-value

= 0.2804

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-13.07

Confidence interval

level

60%

sides

2-sided

lower limit

-23.26

upper limit

-2.88

Variability estimate

Standard error of the mean

Dispersion value

12.1

Notes
[207] - 'Standard error of the mean' refers to 'standard error of the mean difference'

Secondary: LS Means of Total Serum High Density Lipoprotein (HDL) Cholesterol Levels (mg/dL) by Visit

Top of page

End point title

LS Means of Total Serum High Density Lipoprotein (HDL) Cholesterol Levels (mg/dL) by Visit

End point description

End point type

Secondary

End point timeframe

Months 15, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72

End point values	Cyclosporine (CsA)	Tofacitinib Less Intensive (LI)	Tofacitinib More Intensive (MI)
Number of subjects analysed	64	60	54
Units: mg/dL
least squares mean (standard error)
Month 15 (n=59,59,49)	49.88 ( 1.75 )	59.67 ( 1.79 )	55.2 ( 1.93 )
Month 18 (n=59,59,49)	50.47 ( 1.77 )	59.87 ( 1.79 )	55.78 ( 1.95 )
Month 24 (n=58,54,40)	51.47 ( 1.79 )	59.84 ( 1.84 )	53.52 ( 2.08 )
Month 30 (n=52,37,26)	49.55 ( 1.85 )	60.45 ( 2.1 )	53.84 ( 2.47 )
Month 36 (n=51,32,15)	50.46 ( 1.89 )	59.92 ( 2.3 )	54.59 ( 3.17 )
Month 42 (n=44,31,15)	53.24 ( 2 )	59.32 ( 2.4 )	58.59 ( 3.41 )
Month 48 (n=42,30,14)	54.59 ( 2.07 )	61.67 ( 2.45 )	53.55 ( 3.57 )
Month 54 (n=41,31,13)	54.55 ( 2.11 )	60.18 ( 2.45 )	52.38 ( 3.7 )
Month 60 (n=37,23,12)	54.72 ( 2.2 )	60.2 ( 2.71 )	58.98 ( 3.84 )
Month 66 (n=34,20,11)	54.69 ( 2.29 )	62.12 ( 2.9 )	56.08 ( 4.03 )
Month 72 (31,17,11)	52.8 ( 2.4 )	58.8 ( 3.14 )	54.93 ( 4.1 )

LS Means of Total Serum HDL Cholesterol Levels

Statistical analysis description

Month 15

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[208]

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

9.79

Confidence interval

level

60%

sides

2-sided

lower limit

7.68

upper limit

11.9

Variability estimate

Standard error of the mean

Dispersion value

2.5

Notes
[208] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of Total Serum HDL Cholesterol Levels

Statistical analysis description

Month 15

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[209]

P-value

= 0.0418

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

5.32

Confidence interval

level

60%

sides

2-sided

lower limit

3.12

upper limit

7.52

Variability estimate

Standard error of the mean

Dispersion value

2.61

Notes
[209] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of Total Serum HDL Cholesterol Levels

Statistical analysis description

Month 18

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[210]

P-value

= 0.0002

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

9.4

Confidence interval

level

60%

sides

2-sided

lower limit

7.28

upper limit

11.51

Variability estimate

Standard error of the mean

Dispersion value

2.51

Notes
[210] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of Total Serum HDL Cholesterol Levels

Statistical analysis description

Month 18

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[211]

P-value

= 0.0437

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

5.3

Confidence interval

level

60%

sides

2-sided

lower limit

3.09

upper limit

7.51

Variability estimate

Standard error of the mean

Dispersion value

2.63

Notes
[211] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of Total Serum HDL Cholesterol Levels

Statistical analysis description

Month 24

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[212]

P-value

= 0.0011

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

8.37

Confidence interval

level

60%

sides

2-sided

lower limit

6.21

upper limit

10.53

Variability estimate

Standard error of the mean

Dispersion value

2.56

Notes
[212] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of Total Serum HDL Cholesterol Levels

Statistical analysis description

Month 24

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[213]

P-value

= 0.4565

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

2.04

Confidence interval

level

60%

sides

2-sided

lower limit

-0.27

upper limit

4.36

Variability estimate

Standard error of the mean

Dispersion value

2.75

Notes
[213] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of Total Serum HDL Cholesterol Levels

Statistical analysis description

Month 30

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[214]

P-value

= 0.0001

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

10.9

Confidence interval

level

60%

sides

2-sided

lower limit

8.54

upper limit

13.26

Variability estimate

Standard error of the mean

Dispersion value

2.8

Notes
[214] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of Total Serum HDL Cholesterol Levels

Statistical analysis description

Month 30

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[215]

P-value

= 0.1654

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

4.29

Confidence interval

level

60%

sides

2-sided

lower limit

1.69

upper limit

6.89

Variability estimate

Standard error of the mean

Dispersion value

3.09

Notes
[215] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of Total Serum HDL Cholesterol Levels

Statistical analysis description

Month 36

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[216]

P-value

= 0.0015

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

9.45

Confidence interval

level

60%

sides

2-sided

lower limit

6.95

upper limit

11.96

Variability estimate

Standard error of the mean

Dispersion value

2.98

Notes
[216] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of Total Serum HDL Cholesterol Levels

Statistical analysis description

Month 36

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[217]

P-value

= 0.2636

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

4.13

Confidence interval

level

60%

sides

2-sided

lower limit

1.02

upper limit

7.23

Variability estimate

Standard error of the mean

Dispersion value

3.69

Notes
[217] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of Total Serum HDL Cholesterol Levels

Statistical analysis description

Month 42

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[218]

P-value

= 0.052

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

6.08

Confidence interval

level

60%

sides

2-sided

lower limit

3.45

upper limit

8.71

Variability estimate

Standard error of the mean

Dispersion value

3.12

Notes
[218] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of Total Serum HDL Cholesterol Levels

Statistical analysis description

Month 42

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[219]

P-value

= 0.176

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

5.35

Confidence interval

level

60%

sides

2-sided

lower limit

2.02

upper limit

8.67

Variability estimate

Standard error of the mean

Dispersion value

3.95

Notes
[219] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of Total Serum HDL Cholesterol Levels

Statistical analysis description

Month 48

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[220]

P-value

= 0.0274

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

7.08

Confidence interval

level

60%

sides

2-sided

lower limit

4.38

upper limit

9.77

Variability estimate

Standard error of the mean

Dispersion value

3.2

Notes
[220] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of Total Serum HDL Cholesterol Levels

Statistical analysis description

Month 48

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[221]

P-value

= 0.8018

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-1.04

Confidence interval

level

60%

sides

2-sided

lower limit

-4.51

upper limit

2.44

Variability estimate

Standard error of the mean

Dispersion value

4.13

Notes
[221] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of Total Serum HDL Cholesterol Levels

Statistical analysis description

Month 54

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[222]

P-value

= 0.0819

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

5.63

Confidence interval

level

60%

sides

2-sided

lower limit

2.91

upper limit

8.35

Variability estimate

Standard error of the mean

Dispersion value

3.23

Notes
[222] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of Total Serum HDL Cholesterol Levels

Statistical analysis description

Month 54

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[223]

P-value

= 0.6103

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-2.17

Confidence interval

level

60%

sides

2-sided

lower limit

-5.75

upper limit

1.41

Variability estimate

Standard error of the mean

Dispersion value

4.26

Notes
[223] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of Total Serum HDL Cholesterol Levels

Statistical analysis description

Month 60

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[224]

P-value

= 0.1168

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

5.48

Confidence interval

level

60%

sides

2-sided

lower limit

2.54

upper limit

8.41

Variability estimate

Standard error of the mean

Dispersion value

3.49

Notes
[224] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of Total Serum HDL Cholesterol Levels

Statistical analysis description

Month 60

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[225]

P-value

= 0.3357

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

4.26

Confidence interval

level

60%

sides

2-sided

lower limit

0.54

upper limit

7.99

Variability estimate

Standard error of the mean

Dispersion value

4.43

Notes
[225] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of Total Serum HDL Cholesterol Levels

Statistical analysis description

Month 66

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[226]

P-value

= 0.0448

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

7.42

Confidence interval

level

60%

sides

2-sided

lower limit

4.31

upper limit

10.54

Variability estimate

Standard error of the mean

Dispersion value

3.7

Notes
[226] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of Total Serum HDL Cholesterol Levels

Statistical analysis description

Month 66

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[227]

P-value

= 0.7642

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

1.39

Confidence interval

level

60%

sides

2-sided

lower limit

-2.51

upper limit

5.29

Variability estimate

Standard error of the mean

Dispersion value

4.64

Notes
[227] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of Total Serum HDL Cholesterol Levels

Statistical analysis description

Month 72

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[228]

P-value

= 0.1295

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

5.99

Confidence interval

level

60%

sides

2-sided

lower limit

2.67

upper limit

9.32

Variability estimate

Standard error of the mean

Dispersion value

3.95

Notes
[228] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of Total Serum HDL Cholesterol Levels

Statistical analysis description

Month 72

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[229]

P-value

= 0.654

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

2.13

Confidence interval

level

60%

sides

2-sided

lower limit

-1.87

upper limit

6.13

Variability estimate

Standard error of the mean

Dispersion value

4.75

Notes
[229] - 'Standard error of the mean' refers to 'standard error of the mean difference'

Secondary: LS Means of Total Serum Triglycerides (mg/dL) by Visit

Top of page

End point title

LS Means of Total Serum Triglycerides (mg/dL) by Visit

End point description

End point type

Secondary

End point timeframe

Month 15, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72

End point values	Cyclosporine (CsA)	Tofacitinib Less Intensive (LI)	Tofacitinib More Intensive (MI)
Number of subjects analysed	64	60	54
Units: mg/dL
least squares mean (standard error)
Month 15 (n=59,59,49)	177.33 ( 13.66 )	171.21 ( 13.94 )	167.38 ( 15.07 )
Month 18 (n=59,59,49)	181.92 ( 13.74 )	163.26 ( 13.97 )	145.05 ( 15.18 )
Month 24 (n=58,54,40)	183.79 ( 13.93 )	162.8 ( 14.33 )	142.07 ( 16.23 )
Month 30 (n=52,37,26)	182.49 ( 14.44 )	137.05 ( 16.28 )	178.56 ( 19.18 )
Month 36 (n=51,32,15)	174.01 ( 14.73 )	145.27 ( 17.85 )	152.98 ( 24.5 )
Month 42 (n=44,31,15)	178.93 ( 15.55 )	183.09 ( 18.64 )	148.62 ( 26.42 )
Month 48 (n=42,30,14)	166.38 ( 16.08 )	196.86 ( 19.04 )	156.12 ( 27.76 )
Month 54 (n=41,31,13)	163.57 ( 16.41 )	169.18 ( 19.07 )	178.24 ( 28.75 )
Month 60 (n=37,23,12)	156.27 ( 17.1 )	173.2 ( 21.06 )	142.27 ( 29.89 )
Month 66 (n=34,20,11)	165.83 ( 17.82 )	174.19 ( 22.54 )	158.73 ( 31.35 )
Month 72 (n=31,17,11)	143.03 ( 18.63 )	165.1 ( 24.4 )	161.28 ( 31.94 )

LS Means of Total Serum Triglycerides

Statistical analysis description

Month 15

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[230]

P-value

= 0.7543

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-6.11

Confidence interval

level

60%

sides

2-sided

lower limit

-22.55

upper limit

10.33

Variability estimate

Standard error of the mean

Dispersion value

19.53

Notes
[230] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of Total Serum Triglycerides

Statistical analysis description

Month 15

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[231]

P-value

= 0.6249

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-9.95

Confidence interval

level

60%

sides

2-sided

lower limit

-27.07

upper limit

7.17

Variability estimate

Standard error of the mean

Dispersion value

20.33

Notes
[231] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of Total Serum Triglycerides

Statistical analysis description

Month 18

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[232]

P-value

= 0.3415

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-18.66

Confidence interval

level

60%

sides

2-sided

lower limit

-35.17

upper limit

-2.15

Variability estimate

Standard error of the mean

Dispersion value

19.61

Notes
[232] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of Total Serum Triglycerides

Statistical analysis description

Month 18

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[233]

P-value

= 0.072

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-36.86

Confidence interval

level

60%

sides

2-sided

lower limit

-54.1

upper limit

-19.63

Variability estimate

Standard error of the mean

Dispersion value

20.47

Notes
[233] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of Total Serum Triglycerides

Statistical analysis description

Month 24

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[234]

P-value

= 0.2937

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-21

Confidence interval

level

60%

sides

2-sided

lower limit

-37.83

upper limit

-4.17

Variability estimate

Standard error of the mean

Dispersion value

19.99

Notes
[234] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of Total Serum Triglycerides

Statistical analysis description

Month 24

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[235]

P-value

= 0.0512

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-41.72

Confidence interval

level

60%

sides

2-sided

lower limit

-59.72

upper limit

-23.73

Variability estimate

Standard error of the mean

Dispersion value

21.38

Notes
[235] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of Total Serum Triglycerides

Statistical analysis description

Month 30

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[236]

P-value

= 0.037

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-45.43

Confidence interval

level

60%

sides

2-sided

lower limit

-63.75

upper limit

-27.11

Variability estimate

Standard error of the mean

Dispersion value

21.76

Notes
[236] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of Total Serum Triglycerides

Statistical analysis description

Month 30

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[237]

P-value

= 0.8701

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-3.92

Confidence interval

level

60%

sides

2-sided

lower limit

-24.13

upper limit

16.28

Variability estimate

Standard error of the mean

Dispersion value

Notes
[237] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of Total Serum Triglycerides

Statistical analysis description

Month 36

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[238]

P-value

= 0.2146

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-28.75

Confidence interval

level

60%

sides

2-sided

lower limit

-48.24

upper limit

-9.25

Variability estimate

Standard error of the mean

Dispersion value

23.15

Notes
[238] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of Total Serum Triglycerides

Statistical analysis description

Month 36

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[239]

P-value

= 0.462

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-21.03

Confidence interval

level

60%

sides

2-sided

lower limit

-45.09

upper limit

3.03

Variability estimate

Standard error of the mean

Dispersion value

28.58

Notes
[239] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of Total Serum Triglycerides

Statistical analysis description

Month 42

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[240]

P-value

= 0.8639

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

4.16

Confidence interval

level

60%

sides

2-sided

lower limit

-16.28

upper limit

24.6

Variability estimate

Standard error of the mean

Dispersion value

24.28

Notes
[240] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of Total Serum Triglycerides

Statistical analysis description

Month 42

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[241]

P-value

= 0.323

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-30.3

Confidence interval

level

60%

sides

2-sided

lower limit

-56.11

upper limit

-4.5

Variability estimate

Standard error of the mean

Dispersion value

30.65

Notes
[241] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of Total Serum Triglycerides

Statistical analysis description

Month 48

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[242]

P-value

= 0.2214

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

30.49

Confidence interval

level

60%

sides

2-sided

lower limit

9.51

upper limit

51.47

Variability estimate

Standard error of the mean

Dispersion value

24.92

Notes
[242] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of Total Serum Triglycerides

Statistical analysis description

Month 48

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[243]

P-value

= 0.7492

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-10.25

Confidence interval

level

60%

sides

2-sided

lower limit

-37.26

upper limit

16.75

Variability estimate

Standard error of the mean

Dispersion value

32.08

Notes
[243] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of Total Serum Triglycerides

Statistical analysis description

Month 54

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[244]

P-value

= 0.8236

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

5.61

Confidence interval

level

60%

sides

2-sided

lower limit

-15.57

upper limit

26.79

Variability estimate

Standard error of the mean

Dispersion value

25.15

Notes
[244] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of Total Serum Triglycerides

Statistical analysis description

Month 54

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[245]

P-value

= 0.6578

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

14.67

Confidence interval

level

60%

sides

2-sided

lower limit

-13.2

upper limit

42.54

Variability estimate

Standard error of the mean

Dispersion value

33.1

Notes
[245] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of Total Serum Triglycerides

Statistical analysis description

Month 60

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[246]

P-value

= 0.5326

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

16.93

Confidence interval

level

60%

sides

2-sided

lower limit

-5.9

upper limit

39.76

Variability estimate

Standard error of the mean

Dispersion value

27.12

Notes
[246] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of Total Serum Triglycerides

Statistical analysis description

Month 60

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[247]

P-value

= 0.6845

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-14

Confidence interval

level

60%

sides

2-sided

lower limit

-42.99

upper limit

Variability estimate

Standard error of the mean

Dispersion value

34.44

Notes
[247] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of Total Serum Triglycerides

Statistical analysis description

Month 66

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[248]

P-value

= 0.7713

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

8.35

Confidence interval

level

60%

sides

2-sided

lower limit

-15.83

upper limit

32.54

Variability estimate

Standard error of the mean

Dispersion value

28.73

Notes
[248] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of Total Serum Triglycerides

Statistical analysis description

Month 66

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[249]

P-value

= 0.8438

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-7.11

Confidence interval

level

60%

sides

2-sided

lower limit

-37.47

upper limit

23.26

Variability estimate

Standard error of the mean

Dispersion value

36.06

Notes
[249] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of Total Serum Triglycerides

Statistical analysis description

Month 72

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[250]

P-value

= 0.4724

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

22.06

Confidence interval

level

60%

sides

2-sided

lower limit

-3.78

upper limit

47.91

Variability estimate

Standard error of the mean

Dispersion value

30.7

Notes
[250] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of Total Serum Triglycerides

Statistical analysis description

Month 72

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[251]

P-value

= 0.6218

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

18.25

Confidence interval

level

60%

sides

2-sided

lower limit

-12.89

upper limit

49.38

Variability estimate

Standard error of the mean

Dispersion value

36.98

Notes
[251] - 'Standard error of the mean' refers to 'standard error of the mean difference'

Secondary: Mean Absolute Neutrophil Counts (ANC) (kelvin per millimeter cubed [K/mm^3]) by Visit

Top of page

End point title

Mean Absolute Neutrophil Counts (ANC) (kelvin per millimeter cubed [K/mm^3]) by Visit

End point description

Follow-up visit included Month 74 visit for completers and 2-month postdose visit for early withdrawals.

End point type

Secondary

End point timeframe

Months 15, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72 and Follow-up

End point values	Cyclosporine (CsA)	Tofacitinib Less Intensive (LI)	Tofacitinib More Intensive (MI)
Number of subjects analysed	64	60	54
Units: k/mm^3
arithmetic mean (standard deviation)
Month 15 (n=55,56,47)	4.53 ( 1.82 )	4.23 ( 1.79 )	4.33 ( 1.76 )
Month 18 (n=59,58,49)	4.59 ( 1.98 )	3.87 ( 1.57 )	4.83 ( 2.84 )
Month 24 (n=54,52,39)	4.62 ( 1.93 )	3.99 ( 1.43 )	4.38 ( 1.55 )
Month 30 (n=48,35,26)	4.69 ( 1.91 )	3.48 ( 1.25 )	4.55 ( 1.71 )
Month 36 (n=51,30,15)	4.48 ( 1.93 )	3.72 ( 1.41 )	4.62 ( 1.22 )
Month 42 (n=40,31,15)	4.3 ( 1.8 )	3.9 ( 1.76 )	4.49 ( 0.81 )
Month 48 (n=41,30,13)	3.86 ( 1.93 )	3.47 ( 1.58 )	3.86 ( 1.59 )
Month 54 (n=38,26,11)	4.11 ( 1.78 )	3.42 ( 1.09 )	4.27 ( 1.52 )
Month 60 (n=37,20,11)	4.3 ( 1.8 )	3.97 ( 1.57 )	4.01 ( 1.24 )
Month 66 (n=34,19,11)	4.53 ( 1.85 )	3.86 ( 1.51 )	4.28 ( 1.21 )
Month 72 (n=31,17,11)	4.33 ( 1.85 )	3.44 ( 1.12 )	4.73 ( 1.47 )
Follow-up (n=51,46,41)	4.65 ( 1.77 )	3.75 ( 1.26 )	4.37 ( 1.97 )

No statistical analyses for this end point

Secondary: Mean Hemoglobin (Hgb) (grams per deciliter [g/dL]) by Visit

Top of page

End point title

Mean Hemoglobin (Hgb) (grams per deciliter [g/dL]) by Visit

End point description

Follow-up visit included Month 74 visit for completers and 2-month postdose visit for early withdrawals.

End point type

Secondary

End point timeframe

Months 15, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72 and Follow-up

End point values	Cyclosporine (CsA)	Tofacitinib Less Intensive (LI)	Tofacitinib More Intensive (MI)
Number of subjects analysed	64	60	54
Units: g/dL
arithmetic mean (standard deviation)
Month 15 (n=58,59,48)	13.2 ( 1.78 )	13.14 ( 1.41 )	13.35 ( 1.65 )
Month 18 (n=59,59,49)	13.15 ( 1.71 )	13.31 ( 1.13 )	13.5 ( 1.86 )
Month 24 (n=57,54,41)	13.35 ( 1.58 )	13.58 ( 1.25 )	13.58 ( 1.54 )
Month 30 (n=48,37,28)	13.21 ( 1.66 )	13.66 ( 1.23 )	13.82 ( 1.6 )
Month 36 (n=52,32,15)	13.3 ( 1.59 )	13.91 ( 1.08 )	13.44 ( 1.94 )
Month 42 (n=41,31,15)	13.24 ( 1.6 )	13.99 ( 0.99 )	13.67 ( 1.7 )
Month 48 (n=42,31,13)	13.05 ( 1.71 )	14.01 ( 1.18 )	13.28 ( 1.45 )
Month 54 (n=40,29,11)	13.22 ( 1.53 )	13.98 ( 1.31 )	13.6 ( 1.54 )
Month 60 (n=37,20,12)	13.29 ( 1.56 )	14.4 ( 1.24 )	13.41 ( 1.94 )
Month 66 (n=34,19,11)	13.02 ( 1.88 )	14.62 ( 1.18 )	13.42 ( 2.14 )
Month 72 (n=31,17,11)	13.1 ( 1.84 )	14.22 ( 1.56 )	13.23 ( 2.03 )
Follow-up (n=51,47,41)	12.49 ( 2.04 )	13.23 ( 1.75 )	13.72 ( 2.09 )

No statistical analyses for this end point

Secondary: Mean Glycosylated Hemoglobin (HBA1c) (%) by Visit

Top of page

End point title

Mean Glycosylated Hemoglobin (HBA1c) (%) by Visit

End point description

HbA1c is a form of hemoglobin which is measured primarily to identify the average plasma glucose concentration over prolonged periods of time. The normal range for the HbA1c test is between 4 percent (%) and 5.6%. HbA1c levels between 5.7% and 6.4% indicate increased risk of diabetes and levels of 6.5% or higher indicate diabetes.

End point type

Secondary

End point timeframe

Months 24, 36, 48, 60, 72

End point values	Cyclosporine (CsA)	Tofacitinib Less Intensive (LI)	Tofacitinib More Intensive (MI)
Number of subjects analysed	64	60	54
Units: Percentage
arithmetic mean (standard deviation)
Month 24 n=(55,51,35)	6.35 ( 1.84 )	6.16 ( 1.53 )	6.37 ( 1.4 )
Month 36 (n=50,32,15)	6.16 ( 1.39 )	5.92 ( 1.2 )	6.69 ( 2.31 )
Month 48 (n=43,31,14)	6.15 ( 1.64 )	6.16 ( 1.88 )	6.59 ( 1.71 )
Month 60 (n=37,23,12)	6.36 ( 1.94 )	6.26 ( 2.03 )	6.28 ( 1.88 )
Month 72 (n=31,16,11)	6.52 ( 1.98 )	6.34 ( 1.57 )	6.33 ( 2.21 )

No statistical analyses for this end point

Secondary: LS Means of Fasting Serum Glucose Levels (mg/dL) by Visit

Top of page

End point title

LS Means of Fasting Serum Glucose Levels (mg/dL) by Visit

End point description

Model contained treatment, visit and treatment by visit interaction as fixed effects and Baseline (predose in Study A3921030) as a covariate. A compund symmetry variance-covariance structure was used.

End point type

Secondary

End point timeframe

Months 15, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72

End point values	Cyclosporine (CsA)	Tofacitinib Less Intensive (LI)	Tofacitinib More Intensive (MI)
Number of subjects analysed	64	60	54
Units: mg/dL
least squares mean (standard error)
Month 15 (n=59,58,49)	104.42 ( 5.56 )	102.1 ( 5.66 )	107.18 ( 6.13 )
Month 18 (n=59,59,49)	113.01 ( 5.57 )	106.17 ( 5.63 )	107.56 ( 6.13 )
Month 24 (n=58,54,41)	112.23 ( 5.6 )	107.81 ( 5.79 )	102.47 ( 6.5 )
Month 30 (n=50,38,27)	105.27 ( 5.87 )	108.01 ( 6.53 )	107.7 ( 7.55 )
Month 36 (n=51,32,15)	95.88 ( 5.84 )	106.27 ( 6.95 )	106.03 ( 9.55 )
Month 42 (n=44,31,15)	107.1 ( 6.14 )	114.43 ( 7.03 )	94.16 ( 9.55 )
Month 48 (n=42,30,14)	101.14 ( 6.23 )	109.86 ( 7.12 )	104.07 ( 9.83 )
Month 54 (n=41,31,13)	114.5 ( 6.29 )	110.62 ( 7.04 )	127.38 ( 10.13 )
Month 60 (n=37,23,12)	109.75 ( 6.52 )	106.64 ( 7.88 )	107.49 ( 10.49 )
Month 66 (n=34,20,11)	104.42 ( 6.72 )	103.25 ( 8.33 )	108.55 ( 10.88 )
Month 72 (n=30,17,11)	107.01 ( 7.04 )	105.22 ( 8.89 )	99.82 ( 10.88 )

LS Means of Fasting Serum Glucose Levels

Statistical analysis description

Month 15

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[252]

P-value

= 0.7693

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-2.33

Confidence interval

level

60%

sides

2-sided

lower limit

-9.01

upper limit

4.35

Variability estimate

Standard error of the mean

Dispersion value

7.93

Notes
[252] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of Fasting Serum Glucose Levels

Statistical analysis description

Month 15

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[253]

P-value

= 0.7396

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

2.75

Confidence interval

level

60%

sides

2-sided

lower limit

-4.22

upper limit

9.73

Variability estimate

Standard error of the mean

Dispersion value

8.28

Notes
[253] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of Fasting Serum Glucose Levels

Statistical analysis description

Month 18

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[254]

P-value

= 0.3881

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-6.84

Confidence interval

level

60%

sides

2-sided

lower limit

-13.51

upper limit

-0.17

Variability estimate

Standard error of the mean

Dispersion value

7.92

Notes
[254] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of Fasting Serum Glucose Levels

Statistical analysis description

Month 18

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[255]

P-value

= 0.5114

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-5.44

Confidence interval

level

60%

sides

2-sided

lower limit

-12.42

upper limit

1.53

Variability estimate

Standard error of the mean

Dispersion value

8.28

Notes
[255] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of Fasting Serum Glucose Levels

Statistical analysis description

Month 24

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[256]

P-value

= 0.5829

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-4.43

Confidence interval

level

60%

sides

2-sided

lower limit

-11.21

upper limit

2.36

Variability estimate

Standard error of the mean

Dispersion value

8.06

Notes
[256] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of Fasting Serum Glucose Levels

Statistical analysis description

Month 24

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[257]

P-value

= 0.2559

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-9.76

Confidence interval

level

60%

sides

2-sided

lower limit

-16.99

upper limit

-2.53

Variability estimate

Standard error of the mean

Dispersion value

8.58

Notes
[257] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of Fasting Serum Glucose Levels

Statistical analysis description

Month 30

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[258]

P-value

= 0.7548

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

2.74

Confidence interval

level

60%

sides

2-sided

lower limit

-4.65

upper limit

10.14

Variability estimate

Standard error of the mean

Dispersion value

8.78

Notes
[258] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of Fasting Serum Glucose Levels

Statistical analysis description

Match 30

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[259]

P-value

= 0.7998

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

2.43

Confidence interval

level

60%

sides

2-sided

lower limit

-5.63

upper limit

10.49

Variability estimate

Standard error of the mean

Dispersion value

9.57

Notes
[259] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of Fasting Serum Glucose Levels

Statistical analysis description

Month 36

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[260]

P-value

= 0.2531

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

10.39

Confidence interval

level

60%

sides

2-sided

lower limit

2.74

upper limit

18.03

Variability estimate

Standard error of the mean

Dispersion value

9.08

Notes
[260] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of Fasting Serum Glucose Levels

Statistical analysis description

Month 36

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[261]

P-value

= 0.365

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

10.14

Confidence interval

level

60%

sides

2-sided

lower limit

0.72

upper limit

19.57

Variability estimate

Standard error of the mean

Dispersion value

11.2

Notes
[261] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of Fasting Serum Glucose Levels

Statistical analysis description

Month 42

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[262]

P-value

= 0.4328

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

7.33

Confidence interval

level

60%

sides

2-sided

lower limit

-0.53

upper limit

15.19

Variability estimate

Standard error of the mean

Dispersion value

9.34

Notes
[262] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of Fasting Serum Glucose Levels

Statistical analysis description

Month 42

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[263]

P-value

= 0.2547

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-12.94

Confidence interval

level

60%

sides

2-sided

lower limit

-22.5

upper limit

-3.38

Variability estimate

Standard error of the mean

Dispersion value

11.35

Notes
[263] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of Fasting Serum Glucose Levels

Statistical analysis description

Month 48

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[264]

P-value

= 0.3572

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

8.72

Confidence interval

level

60%

sides

2-sided

lower limit

0.75

upper limit

16.69

Variability estimate

Standard error of the mean

Dispersion value

9.46

Notes
[264] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of Fasting Serum Glucose Levels

Statistical analysis description

Month 48

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[265]

P-value

= 0.8009

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

2.94

Confidence interval

level

60%

sides

2-sided

lower limit

-6.86

upper limit

12.74

Variability estimate

Standard error of the mean

Dispersion value

11.64

Notes
[265] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of Fasting Serum Glucose Levels

Statistical analysis description

Month 54

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[266]

P-value

= 0.6814

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-3.88

Confidence interval

level

60%

sides

2-sided

lower limit

-11.82

upper limit

4.07

Variability estimate

Standard error of the mean

Dispersion value

9.44

Notes
[266] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of Fasting Serum Glucose Levels

Statistical analysis description

Month 54

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[267]

P-value

= 0.2803

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

12.88

Confidence interval

level

60%

sides

2-sided

lower limit

2.84

upper limit

22.93

Variability estimate

Standard error of the mean

Dispersion value

11.93

Notes
[267] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of Fasting Serum Glucose Levels

Statistical analysis description

Month 60

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[268]

P-value

= 0.7613

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-3.11

Confidence interval

level

60%

sides

2-sided

lower limit

-11.72

upper limit

5.5

Variability estimate

Standard error of the mean

Dispersion value

10.23

Notes
[268] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of Fasting Serum Glucose Levels

Statistical analysis description

Month 60

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[269]

P-value

= 0.8554

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-2.25

Confidence interval

level

60%

sides

2-sided

lower limit

-12.65

upper limit

8.15

Variability estimate

Standard error of the mean

Dispersion value

12.35

Notes
[269] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of Fasting Serum Glucose Levels

Statistical analysis description

Month 66

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[270]

P-value

= 0.9132

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-1.17

Confidence interval

level

60%

sides

2-sided

lower limit

-10.18

upper limit

7.84

Variability estimate

Standard error of the mean

Dispersion value

10.7

Notes
[270] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of Fasting Serum Glucose Levels

Statistical analysis description

Month 66

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[271]

P-value

= 0.7465

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

4.14

Confidence interval

level

60%

sides

2-sided

lower limit

-6.63

upper limit

14.9

Variability estimate

Standard error of the mean

Dispersion value

12.79

Notes
[271] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of Fasting Serum Glucose Levels

Statistical analysis description

Month 72

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[272]

P-value

= 0.8747

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-1.79

Confidence interval

level

60%

sides

2-sided

lower limit

-11.34

upper limit

7.76

Variability estimate

Standard error of the mean

Dispersion value

11.34

Notes
[272] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of Fasting Serum Glucose Levels

Statistical analysis description

Month 72

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[273]

P-value

= 0.5793

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-7.19

Confidence interval

level

60%

sides

2-sided

lower limit

-18.1

upper limit

3.72

Variability estimate

Standard error of the mean

Dispersion value

12.96

Notes
[273] - 'Standard error of the mean' refers to 'standard error of the mean difference'

Secondary: Percentage of Participants by Proteinuria Category by Visit

Top of page

End point title

Percentage of Participants by Proteinuria Category by Visit

End point description

Proteinuria was defined as the presence of an excess of serum proteins in the urine. Normal value of proteinuria is below 0.15 grams per 24 hours (g/24 hr). Follow-up visit included Month 74 visit for completers and 2-month postdose visit for early withdrawals.

End point type

Secondary

End point timeframe

Months 24, 36, 48, 60, 72 and Follow-up

End point values	Cyclosporine (CsA)	Tofacitinib Less Intensive (LI)	Tofacitinib More Intensive (MI)
Number of subjects analysed	64	60	54
Units: Percentage of Participants
number (not applicable)
Month 24: >200 mg/day (n=51,47,36)	15.7	27.7	19.4
Month 24: >500 mg/day (n=51,47,36)	3.9	6.4	8.3
Month 24: >1500 mg/day (n=51,47,36)	2	2.1	5.6
Month 24: >500 Increase from Baseline (n=51,47,36)	2	0	0
Month 36: >200 mg/day (n=42,30,13)	14.3	26.7	15.4
Month 36: >500 mg/day (n=42,30,13)	2.4	3.3	0
Month 36: >1500 mg/day (n=42,30,13)	2.4	3.3	0
Month 36: >500 Increase from Baseline (n=42,30,13)	0	0	0
Month 48: >200 mg/day (n=36,29,12)	16.7	31	0
Month 48: >500 mg/day (n=36,29,12)	5.6	17.2	0
Month 48: >1500 mg/day (n=36,29,12)	2.8	6.9	0
Month 48: >500 Increase in Baseline (n=36,29,12)	0	3.4	0
Month 60: >200 mg/day (n=29,20,10)	10.3	20	10
Month 60: >500 mg/day (n=29,20,10)	10.3	15	0
Month 60: >1500 mg/day (n=29,20,10)	3.4	5	0
Month 60: >500 Increase in Baseline (n=29,20,10)	0	5	0
Month 72: >200 mg/day (n=22,15,9)	9.1	20	22.2
Month 72: >500 mg/day (n=22,15,9)	4.5	20	11.1
Month 72: >1500 mg/day (n=22,15,9)	0	13.3	0
Month 72: >500 Increase in Baseline (n=22,15,9)	0	0	11.1
Follow-up: >200 mg/day (n=46,34,39)	13	17.6	20.5
Follow-up: >500 mg/day (n=46,34,39)	6.5	8.8	5.1
Follow-up: >1500 mg/day (n=46,34,39)	2.2	5.9	2.6
Follow-up: >500 Increase in Baseline (n=46,34,39)	0	0	2.6

No statistical analyses for this end point

Secondary: LS Means of Estimated GFR Calculated Using the Nankivell Equation by Visit

Top of page

End point title

LS Means of Estimated GFR Calculated Using the Nankivell Equation by Visit

End point description

GFR: an index of kidney function. GFR described the flow rate of filtered fluid through the kidney. GFR was measured directly or estimated using established formulas. GFR was calculated using Nankivell formula, where: Creatinine clearance (mL/minute) = 6.7/serum creatinine (millimols per litre [mmol/L]) - serum urea (mmol/dL)/2 + actual body weight (kilograms [kg])/4 - 100/Height (metres)^2 + (35 for male or 25 for female). A normal GFR for adults is > 90 mL/min. Lower values indicate poor kidney function. A GFR <15 is consistent with kidney failure. Model contained treatment, visit and treatment by visit interaction as fixed effects. An unstructured variance-covariance structure was used.

End point type

Secondary

End point timeframe

Month 15, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72

End point values	Cyclosporine (CsA)	Tofacitinib Less Intensive (LI)	Tofacitinib More Intensive (MI)
Number of subjects analysed	64	60	54
Units: minutes per milliliter (min/mL)
least squares mean (standard error)
Month 15 (n=59,59,50)	69.57 ( 1.95 )	82.33 ( 2 )	82.96 ( 2.13 )
Month 18 (n=59,59,50)	70.93 ( 2.09 )	82.41 ( 2.15 )	82.91 ( 2.28 )
Month 24 (n=58,54,41)	69.78 ( 2.09 )	82.63 ( 2.15 )	83.49 ( 2.32 )
Month 30 (n=51,37,27)	68.41 ( 2.28 )	84.27 ( 2.46 )	82.02 ( 2.73 )
Month 36 (n=51,32,15)	68.94 ( 2.44 )	81.1 ( 2.66 )	81.5 ( 3.14 )
Month 42 (n=44,31,15)	68.82 ( 2.29 )	81.24 ( 2.49 )	77.81 ( 2.98 )
Month 48 (n=42,30,14)	67.68 ( 2.54 )	80.08 ( 2.79 )	75.28 ( 3.46 )
Month 54 (n=41,31,13)	65.59 ( 2.69 )	79.63 ( 2.98 )	75.82 ( 3.88 )
Month 60 (n=37,24,12)	70.08 ( 2.46 )	77.8 ( 2.77 )	74.19 ( 3.51 )
Month 66 (n=34,20,11)	68.99 ( 2.8 )	76.74 ( 3.17 )	75.01 ( 4.01 )
Month 72 (n=30,17,11)	68.65 ( 3.39 )	81.68 ( 4.01 )	72.92 ( 5.1 )

LS Means of Estimated GFR - Nankivell Equation

Statistical analysis description

Month 15

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[274]

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

12.76

Confidence interval

level

60%

sides

2-sided

lower limit

10.4

upper limit

15.11

Variability estimate

Standard error of the mean

Dispersion value

2.79

Notes
[274] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of Estimated GFR - Nankivell Equation

Statistical analysis description

Month 15

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[275]

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

13.39

Confidence interval

level

60%

sides

2-sided

lower limit

10.96

upper limit

15.82

Variability estimate

Standard error of the mean

Dispersion value

2.88

Notes
[275] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of Estimated GFR - Nankivell Equation

Statistical analysis description

Month 18

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[276]

P-value

= 0.0002

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

11.48

Confidence interval

level

60%

sides

2-sided

lower limit

8.95

upper limit

Variability estimate

Standard error of the mean

Dispersion value

Notes
[276] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of Estimated GFR - Nankivell Equation

Statistical analysis description

Month 18

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[277]

P-value

= 0.0002

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

11.98

Confidence interval

level

60%

sides

2-sided

lower limit

9.37

upper limit

14.59

Variability estimate

Standard error of the mean

Dispersion value

3.09

Notes
[277] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of estimated GFR - Nankivell Equation

Statistical analysis description

Month 24

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[278]

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

12.86

Confidence interval

level

60%

sides

2-sided

lower limit

10.32

upper limit

15.39

Variability estimate

Standard error of the mean

Dispersion value

Notes
[278] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of Estimated GFR - Nankivell Equation

Statistical analysis description

Month 24

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[279]

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

13.71

Confidence interval

level

60%

sides

2-sided

lower limit

11.08

upper limit

16.35

Variability estimate

Standard error of the mean

Dispersion value

3.12

Notes
[279] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of Estimated GFR - Nankivell Equation

Statistical analysis description

Month 30

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[280]

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

15.86

Confidence interval

level

60%

sides

2-sided

lower limit

13.03

upper limit

18.69

Variability estimate

Standard error of the mean

Dispersion value

3.35

Notes
[280] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of Estimated GFR - Nankivell Equation

Statistical analysis description

Month 30

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[281]

P-value

= 0.0002

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

13.61

Confidence interval

level

60%

sides

2-sided

lower limit

10.61

upper limit

16.61

Variability estimate

Standard error of the mean

Dispersion value

3.56

Notes
[281] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of Estimated GFR - Nankivell Equation

Statistical analysis description

Month 36

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[282]

P-value

= 0.001

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

12.17

Confidence interval

level

60%

sides

2-sided

lower limit

9.12

upper limit

15.21

Variability estimate

Standard error of the mean

Dispersion value

3.61

Notes
[282] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of Estimated GFR - Nankivell Equation

Statistical analysis description

Month 36

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[283]

P-value

= 0.0019

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

12.56

Confidence interval

level

60%

sides

2-sided

lower limit

9.2

upper limit

15.92

Variability estimate

Standard error of the mean

Dispersion value

3.98

Notes
[283] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of Estimated GFR - Nankivell Equation

Statistical analysis description

Month 42

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[284]

P-value

= 0.0004

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

12.42

Confidence interval

level

60%

sides

2-sided

lower limit

9.56

upper limit

15.27

Variability estimate

Standard error of the mean

Dispersion value

3.38

Notes
[284] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of Estimated GFR - Nankivell Equation

Statistical analysis description

Month 42

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[285]

P-value

= 0.0182

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

8.99

Confidence interval

level

60%

sides

2-sided

lower limit

5.81

upper limit

12.16

Variability estimate

Standard error of the mean

Dispersion value

3.76

Notes
[285] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of Estimated GFR - Nankivell Equation

Statistical analysis description

Month 48

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[286]

P-value

= 0.0013

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

12.4

Confidence interval

level

60%

sides

2-sided

lower limit

9.22

upper limit

15.58

Variability estimate

Standard error of the mean

Dispersion value

3.77

Notes
[286] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of Estimated GFR - Nankivell Equation

Statistical analysis description

Month 48

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[287]

P-value

= 0.0782

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

7.6

Confidence interval

level

60%

sides

2-sided

lower limit

3.99

upper limit

11.22

Variability estimate

Standard error of the mean

Dispersion value

4.29

Notes
[287] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of Estimated GFR - Nankivell Equation

Statistical analysis description

Month 54

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[288]

P-value

= 0.0007

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

14.04

Confidence interval

level

60%

sides

2-sided

lower limit

10.64

upper limit

17.43

Variability estimate

Standard error of the mean

Dispersion value

4.02

Notes
[288] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of Estimated GFR - Nankivell Equation

Statistical analysis description

Month 54

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[289]

P-value

= 0.0322

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

10.23

Confidence interval

level

60%

sides

2-sided

lower limit

6.24

upper limit

14.22

Variability estimate

Standard error of the mean

Dispersion value

4.72

Notes
[289] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of Estimated GFR - Nankivell Equation

Statistical analysis description

Month 60

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[290]

P-value

= 0.0399

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

7.72

Confidence interval

level

60%

sides

2-sided

lower limit

4.59

upper limit

10.86

Variability estimate

Standard error of the mean

Dispersion value

3.7

Notes
[290] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of Estimated GFR - Nankivell Equation

Statistical analysis description

Month 60

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[291]

P-value

= 0.3391

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

4.11

Confidence interval

level

60%

sides

2-sided

lower limit

0.49

upper limit

7.73

Variability estimate

Standard error of the mean

Dispersion value

4.28

Notes
[291] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS means of Estimated GFR - Nankivell equation

Statistical analysis description

Month 66

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[292]

P-value

= 0.0702

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

7.75

Confidence interval

level

60%

sides

2-sided

lower limit

4.17

upper limit

11.33

Variability estimate

Standard error of the mean

Dispersion value

4.23

Notes
[292] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of Estimated GFR - Nankivell Equation

Statistical analysis description

Month 66

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[293]

P-value

= 0.221

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

6.02

Confidence interval

level

60%

sides

2-sided

lower limit

1.89

upper limit

10.15

Variability estimate

Standard error of the mean

Dispersion value

4.89

Notes
[293] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of Estimated GFR - Nankivell Equation

Statistical analysis description

Month 72

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[294]

P-value

= 0.015

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

13.03

Confidence interval

level

60%

sides

2-sided

lower limit

8.59

upper limit

17.46

Variability estimate

Standard error of the mean

Dispersion value

5.25

Notes
[294] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of Estimated GFR - Nankivell Equation

Statistical analysis description

Month 72

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[295]

P-value

= 0.4875

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

4.27

Confidence interval

level

60%

sides

2-sided

lower limit

-0.91

upper limit

9.45

Variability estimate

Standard error of the mean

Dispersion value

6.13

Notes
[295] - 'Standard error of the mean' refers to 'standard error of the mean difference'

Secondary: LS Means of Estimated GFR Calculated Using the Cockcroft-Gault Equation by Visit

Top of page

End point title

LS Means of Estimated GFR Calculated Using the Cockcroft-Gault Equation by Visit

End point description

GFR: an index of kidney function. GFR described the flow rate of filtered fluid through the kidney. GFR was measured directly or estimated using established formulas. GFR was calculated using Cockcroft-Gault equation. GFR (mL/min) by Cockcroft-Gault equation= body weight (kg)*(140 minus age in years) divided by (72*serum creatinine [mg/dL]). For females value obtained was multiplied by 0.85. A normal GFR is >90 mL/min, although children and older people usually have a lower GFR. Lower values indicated poor kidney function. A GFR <15 mL/min indicated kidney failure. Model contained treatment, visit and treatment by visit interaction as fixed effects. An unstructured variance-covariance structure was used.

End point type

Secondary

End point timeframe

Months 15, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72

End point values	Cyclosporine (CsA)	Tofacitinib Less Intensive (LI)	Tofacitinib More Intensive (MI)
Number of subjects analysed	64	60	54
Units: min/mL
least squares mean (standard error)
Month 15 (n=59,59,50)	72.74 ( 3.02 )	87.22 ( 3.1 )	87.67 ( 3.29 )
Month 18 (n=59,59,50)	73.56 ( 3.14 )	87.52 ( 3.23 )	87.12 ( 3.42 )
Month 24 (n=58,54,42)	72.7 ( 3.28 )	87.72 ( 3.39 )	87.62 ( 3.62 )
Month 30 (n=51,38,29)	70.7 ( 3.48 )	89.24 ( 3.68 )	87.15 ( 3.99 )
Month 36 (n=51,32,15)	70.71 ( 3.75 )	85.91 ( 4.04 )	85.64 ( 4.68 )
Month 42 (n=44,31,15)	69.63 ( 3.48 )	85.95 ( 3.76 )	81.88 ( 4.45 )
Month 48 (n=42,30,14)	67.63 ( 3.81 )	83.96 ( 4.15 )	77.42 ( 5.03 )
Month 54 (n=41,31,13)	65.81 ( 3.85 )	82.78 ( 4.2 )	77.6 ( 5.26 )
Month 60 (n=37,24,12)	70.52 ( 3.92 )	78.54 ( 4.43 )	74.18 ( 5.63 )
Month 66 (n=34,20,11)	69.09 ( 3.81 )	79.09 ( 4.21 )	74.52 ( 5.11 )
Month 72 (n=30,17,11)	68.34 ( 4.44 )	85.5 ( 5.11 )	73.05 ( 6.45 )

LS Means of Estimated GFR - Cockcroft-Gault

Statistical analysis description

Month 15

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[296]

P-value

= 0.001

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

14.48

Confidence interval

level

60%

sides

2-sided

lower limit

10.83

upper limit

18.13

Variability estimate

Standard error of the mean

Dispersion value

4.33

Notes
[296] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of Estimated GFR - Cockcroft-Gault

Statistical analysis description

Month 15

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[297]

P-value

= 0.001

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

14.93

Confidence interval

level

60%

sides

2-sided

lower limit

11.16

upper limit

18.7

Variability estimate

Standard error of the mean

Dispersion value

4.47

Notes
[297] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of Estimated GFR - Cockcroft-Gault

Statistical analysis description

Month 18

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[298]

P-value

= 0.0023

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

13.96

Confidence interval

level

60%

sides

2-sided

lower limit

10.16

upper limit

17.76

Variability estimate

Standard error of the mean

Dispersion value

4.5

Notes
[298] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of Estimated GFR - Cockcroft-Gault

Statistical analysis description

Month 18

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[299]

P-value

= 0.0039

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

13.57

Confidence interval

level

60%

sides

2-sided

lower limit

9.65

upper limit

17.48

Variability estimate

Standard error of the mean

Dispersion value

4.64

Notes
[299] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS means of Estimated GFR - Cockcroft-Gault

Statistical analysis description

Month 24

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[300]

P-value

= 0.0017

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

15.02

Confidence interval

level

60%

sides

2-sided

lower limit

11.04

upper limit

Variability estimate

Standard error of the mean

Dispersion value

4.72

Notes
[300] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of Estimated GFR - Cockcroft-Gault

Statistical analysis description

Month 24

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[301]

P-value

= 0.0026

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

14.93

Confidence interval

level

60%

sides

2-sided

lower limit

10.81

upper limit

19.04

Variability estimate

Standard error of the mean

Dispersion value

4.88

Notes
[301] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of Estimated GFR - Cockcroft-Gault

Statistical analysis description

Month 30

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[302]

P-value

= 0.0003

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

18.54

Confidence interval

level

60%

sides

2-sided

lower limit

14.27

upper limit

22.81

Variability estimate

Standard error of the mean

Dispersion value

5.06

Notes
[302] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of Estimated GFR - Cockcroft-Gault

Statistical analysis description

Month 30

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[303]

P-value

= 0.0022

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

16.45

Confidence interval

level

60%

sides

2-sided

lower limit

11.99

upper limit

20.91

Variability estimate

Standard error of the mean

Dispersion value

5.29

Notes
[303] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS means of Estimated GFR - Cockcroft-Gault

Statistical analysis description

Month 36

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[304]

P-value

= 0.0065

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

15.19

Confidence interval

level

60%

sides

2-sided

lower limit

10.55

upper limit

19.84

Variability estimate

Standard error of the mean

Dispersion value

5.51

Notes
[304] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of Estimated GFR - Cockcroft-Gault

Statistical analysis description

Month 36

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[305]

P-value

= 0.0137

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

14.93

Confidence interval

level

60%

sides

2-sided

lower limit

9.87

upper limit

19.99

Variability estimate

Standard error of the mean

Dispersion value

Notes
[305] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of Estimated GFR - Cockcroft-Gault

Statistical analysis description

Month 42

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[306]

P-value

= 0.0018

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

16.32

Confidence interval

level

60%

sides

2-sided

lower limit

11.99

upper limit

20.64

Variability estimate

Standard error of the mean

Dispersion value

5.12

Notes
[306] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of Estimated GFR - Cockcroft-Gault

Statistical analysis description

Month 42

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[307]

P-value

= 0.0316

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

12.24

Confidence interval

level

60%

sides

2-sided

lower limit

7.47

upper limit

17.01

Variability estimate

Standard error of the mean

Dispersion value

5.65

Notes
[307] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of Estimated GFR - Cockcroft-Gault

Statistical analysis description

Month 48

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[308]

P-value

= 0.0043

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

16.33

Confidence interval

level

60%

sides

2-sided

lower limit

11.57

upper limit

21.09

Variability estimate

Standard error of the mean

Dispersion value

5.64

Notes
[308] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of Estimated GFR - Cockcroft-Gault

Statistical analysis description

Month 48

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[309]

P-value

= 0.1226

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

9.8

Confidence interval

level

60%

sides

2-sided

lower limit

4.47

upper limit

15.12

Variability estimate

Standard error of the mean

Dispersion value

6.31

Notes
[309] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of Estimated GFR - Cockcroft-Gault

Statistical analysis description

Month 54

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[310]

P-value

= 0.0034

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

16.97

Confidence interval

level

60%

sides

2-sided

lower limit

12.17

upper limit

21.78

Variability estimate

Standard error of the mean

Dispersion value

5.7

Notes
[310] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of Estimated GFR - Cockcroft-Gault

Statistical analysis description

Month 54

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[311]

P-value

= 0.0724

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

11.79

Confidence interval

level

60%

sides

2-sided

lower limit

6.29

upper limit

17.29

Variability estimate

Standard error of the mean

Dispersion value

6.52

Notes
[311] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of Estimated GFR - Cockcroft-Gault

Statistical analysis description

Month 60

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[312]

P-value

= 0.1782

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

8.03

Confidence interval

level

60%

sides

2-sided

lower limit

3.02

upper limit

13.03

Variability estimate

Standard error of the mean

Dispersion value

5.92

Notes
[312] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of Estimated GFR - Cockcroft-Gault

Statistical analysis description

Month 60

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[313]

P-value

= 0.5947

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

3.66

Confidence interval

level

60%

sides

2-sided

lower limit

-2.14

upper limit

9.46

Variability estimate

Standard error of the mean

Dispersion value

6.86

Notes
[313] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of Estimated GFR - Cockcroft-Gault

Statistical analysis description

Month 66

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[314]

P-value

= 0.081

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

9.99

Confidence interval

level

60%

sides

2-sided

lower limit

5.2

upper limit

14.79

Variability estimate

Standard error of the mean

Dispersion value

5.68

Notes
[314] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of Estimated GFR - Cockcroft-Gault

Statistical analysis description

Month 66

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[315]

P-value

= 0.3965

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

5.42

Confidence interval

level

60%

sides

2-sided

lower limit

0.04

upper limit

10.81

Variability estimate

Standard error of the mean

Dispersion value

6.38

Notes
[315] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of Estimated GFR - Cockcroft-Gault

Statistical analysis description

Month 72

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[316]

P-value

= 0.0128

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

17.16

Confidence interval

level

60%

sides

2-sided

lower limit

11.44

upper limit

22.88

Variability estimate

Standard error of the mean

Dispersion value

6.77

Notes
[316] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of Estimated GFR - Cockcroft-Gault

Statistical analysis description

Month 72

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[317]

P-value

= 0.5487

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

4.71

Confidence interval

level

60%

sides

2-sided

lower limit

-1.91

upper limit

11.33

Variability estimate

Standard error of the mean

Dispersion value

7.83

Notes
[317] - 'Standard error of the mean' refers to 'standard error of the mean difference'

Secondary: LS Means of estimated GFR (eGFR) (mL/min/1.73m^2) Calculated by the Modification of Diet in Renal Disease (MDRD) Equation With Last Observation Carried Forward (LOCF) plus Imputation (eGFR=0 for graft loss/death) by Visit

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End point title

LS Means of estimated GFR (eGFR) (mL/min/1.73m^2) Calculated by the Modification of Diet in Renal Disease (MDRD) Equation With Last Observation Carried Forward (LOCF) plus Imputation (eGFR=0 for graft loss/death) by Visit

End point description

GFR: an index of kidney function. GFR described the flow rate of filtered fluid through the kidney. GFR was calculated using MDRD equation. GFR (mL/min/1.73 square meter (m^2) by MDRD equation = 170 * (serum creatinine [mg/dL])^(-0.999) * (age in years)^(-0.176) * (0.762 if female) * (1.18 if black) * (blood urea nitrogen concentration [mg/dL])^(-0.170) * (serum albumin concentration)^(0.318).A normal GFR is >90 mL/min/1.73 m^2, although children and older people usually have a lower GFR. Lower values indicated poor kidney function. A GFR <15 mL/min/1.73 m^2 indicated kidney failure. Model contained treatment, visit and treatment by visit interaction as fixed effects. An unstructured variance-covariance structure was used.

End point type

Secondary

End point timeframe

Months 15, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72

End point values	Cyclosporine (CsA)	Tofacitinib Less Intensive (LI)	Tofacitinib More Intensive (MI)
Number of subjects analysed	64	60	54
Units: mL/min/1.73m^2
least squares mean (standard error)
Month 15	56.25 ( 1.99 )	72.12 ( 2.06 )	70.22 ( 2.17 )
Month 18	58.13 ( 2.32 )	71.66 ( 2.39 )	69.69 ( 2.52 )
Month 24	56.3 ( 2.4 )	71.93 ( 2.47 )	68.2 ( 2.61 )
Month 30	53.82 ( 2.69 )	73.1 ( 2.78 )	64.44 ( 2.93 )
Month 36	54.37 ( 3 )	69.09 ( 3.1 )	63.27 ( 3.26 )
Month 42	53.59 ( 2.96 )	68.29 ( 3.05 )	62.14 ( 3.22 )
Month 48	51.69 ( 3.23 )	65.27 ( 3.34 )	60.81 ( 3.52 )
Month 54	48.64 ( 3.29 )	65.25 ( 3.4 )	60.79 ( 3.59 )
Month 60	50.43 ( 3.3 )	63.82 ( 3.41 )	59.2 ( 3.59 )
Month 66	49.7 ( 3.34 )	63.33 ( 3.45 )	59.47 ( 3.63 )
Month 72	49.62 ( 3.51 )	64.27 ( 3.62 )	59.21 ( 3.82 )

LS Means of Estimated GFR - MDRD Equation (LOCF)

Statistical analysis description

Month 15

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[318]

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

15.87

Confidence interval

level

60%

sides

2-sided

lower limit

13.46

upper limit

18.29

Variability estimate

Standard error of the mean

Dispersion value

2.86

Notes
[318] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of Estimated GFR - MDRD Equation (LOCF)

Statistical analysis description

Month 15

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[319]

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

13.97

Confidence interval

level

60%

sides

2-sided

lower limit

11.49

upper limit

16.46

Variability estimate

Standard error of the mean

Dispersion value

2.95

Notes
[319] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of Estimated GFR - MDRD Equation (LOCF)

Statistical analysis description

Month 18

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[320]

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

13.53

Confidence interval

level

60%

sides

2-sided

lower limit

10.71

upper limit

16.34

Variability estimate

Standard error of the mean

Dispersion value

3.33

Notes
[320] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of Estimated GFR - MDRD Equation (LOCF)

Statistical analysis description

Month 18

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[321]

P-value

= 0.0009

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

11.56

Confidence interval

level

60%

sides

2-sided

lower limit

8.67

upper limit

14.45

Variability estimate

Standard error of the mean

Dispersion value

3.43

Notes
[321] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of Estimated GFR - MDRD Equation (LOCF)

Statistical analysis description

Month 24

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[322]

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

15.63

Confidence interval

level

60%

sides

2-sided

lower limit

12.72

upper limit

18.53

Variability estimate

Standard error of the mean

Dispersion value

3.44

Notes
[322] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of Estimated GFR - MDRD Equation (LOCF)

Statistical analysis description

Month 24

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[323]

P-value

= 0.001

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

11.89

Confidence interval

level

60%

sides

2-sided

lower limit

8.91

upper limit

14.88

Variability estimate

Standard error of the mean

Dispersion value

3.54

Notes
[323] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of Estimated GFR - MDRD Equation (LOCF)

Statistical analysis description

Month 30

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[324]

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

19.29

Confidence interval

level

60%

sides

2-sided

lower limit

16.03

upper limit

22.55

Variability estimate

Standard error of the mean

Dispersion value

3.86

Notes
[324] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of Estimated GFR - MDRD Equation (LOCF)

Statistical analysis description

Month 30

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[325]

P-value

= 0.0082

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

10.63

Confidence interval

level

60%

sides

2-sided

lower limit

7.27

upper limit

13.98

Variability estimate

Standard error of the mean

Dispersion value

3.97

Notes
[325] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of Estimated GFR - MDRD Equation (LOCF)

Statistical analysis description

Month 36

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[326]

P-value

= 0.0008

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

14.72

Confidence interval

level

60%

sides

2-sided

lower limit

11.09

upper limit

18.36

Variability estimate

Standard error of the mean

Dispersion value

4.31

Notes
[326] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of Estimated GFR - MDRD Equation (LOCF)

Statistical analysis description

Month 36

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[327]

P-value

= 0.0462

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

8.9

Confidence interval

level

60%

sides

2-sided

lower limit

5.16

upper limit

12.64

Variability estimate

Standard error of the mean

Dispersion value

4.43

Notes
[327] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of Estimated GFR - MDRD Equation (LOCF)

Statistical analysis description

Month 42

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[328]

P-value

= 0.0007

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

14.7

Confidence interval

level

60%

sides

2-sided

lower limit

11.11

upper limit

18.28

Variability estimate

Standard error of the mean

Dispersion value

4.25

Notes
[328] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of Estimated GFR - MDRD Equation (LOCF)

Statistical analysis description

Month 42

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[329]

P-value

= 0.0519

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

8.55

Confidence interval

level

60%

sides

2-sided

lower limit

4.87

upper limit

12.24

Variability estimate

Standard error of the mean

Dispersion value

4.37

Notes
[329] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of Estimated GFR - MDRD Equation (LOCF)

Statistical analysis description

Month 48

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[330]

P-value

= 0.0039

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

13.58

Confidence interval

level

60%

sides

2-sided

lower limit

9.66

upper limit

17.5

Variability estimate

Standard error of the mean

Dispersion value

4.65

Notes
[330] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of Estimated GFR - MDRD Equation (LOCF)

Statistical analysis description

Month 48

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[331]

P-value

= 0.058

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

9.12

Confidence interval

level

60%

sides

2-sided

lower limit

5.09

upper limit

13.15

Variability estimate

Standard error of the mean

Dispersion value

4.78

Notes
[331] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of Estimated GFR - MDRD Equation (LOCF)

Statistical analysis description

Month 54

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[332]

P-value

= 0.0006

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

16.61

Confidence interval

level

60%

sides

2-sided

lower limit

12.62

upper limit

20.61

Variability estimate

Standard error of the mean

Dispersion value

4.74

Notes
[332] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of Estimated GFR - MDRD Equation (LOCF)

Statistical analysis description

Month 54

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[333]

P-value

= 0.0136

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

12.15

Confidence interval

level

60%

sides

2-sided

lower limit

8.04

upper limit

16.26

Variability estimate

Standard error of the mean

Dispersion value

4.87

Notes
[333] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of Estimated GFR - MDRD Equation (LOCF)

Statistical analysis description

Month 60

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[334]

P-value

= 0.0053

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

13.39

Confidence interval

level

60%

sides

2-sided

lower limit

9.39

upper limit

17.39

Variability estimate

Standard error of the mean

Dispersion value

4.74

Notes
[334] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of Estimated GFR - MDRD Equation (LOCF)

Statistical analysis description

Month 60

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[335]

P-value

= 0.0736

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

8.77

Confidence interval

level

60%

sides

2-sided

lower limit

4.66

upper limit

12.88

Variability estimate

Standard error of the mean

Dispersion value

4.87

Notes
[335] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS means of Estimated GFR - MDRD Equation (LOCF)

Statistical analysis description

Month 66

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[336]

P-value

= 0.005

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

13.63

Confidence interval

level

60%

sides

2-sided

lower limit

9.58

upper limit

17.67

Variability estimate

Standard error of the mean

Dispersion value

4.8

Notes
[336] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of Estimated GFR - MDRD Equation (LOCF)

Statistical analysis description

Month 66

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[337]

P-value

= 0.0491

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

9.77

Confidence interval

level

60%

sides

2-sided

lower limit

5.61

upper limit

13.93

Variability estimate

Standard error of the mean

Dispersion value

4.93

Notes
[337] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of Estimated GFR - MDRD Equation (LOCF)

Statistical analysis description

Month 72

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[338]

P-value

= 0.0041

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

14.66

Confidence interval

level

60%

sides

2-sided

lower limit

10.4

upper limit

18.91

Variability estimate

Standard error of the mean

Dispersion value

5.04

Notes
[338] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of Estimated GFR - MDRD Equation (LOCF)

Statistical analysis description

Month 72

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[339]

P-value

= 0.066

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

9.59

Confidence interval

level

60%

sides

2-sided

lower limit

5.22

upper limit

13.97

Variability estimate

Standard error of the mean

Dispersion value

5.19

Notes
[339] - 'Standard error of the mean' refers to 'standard error of the mean difference'

Secondary: LS Means of Short Form 36 Version 2 (SF-36 V2) Component and Domain Scores at Months 24 and 36

Top of page

End point title

LS Means of Short Form 36 Version 2 (SF-36 V2) Component and Domain Scores at Months 24 and 36

End point description

The SF-36v2 is a self administered, 36-item generic health status measure. It measures 8 general health concepts: Physical Functioning, Role Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role Emotional, and Mental Health. These concepts were also summarized into 2 summary scores, the Physical Component Summary and Mental Component Summary. Higher domain and summary scores indicate better health status. The 8 subscales, 2 composite subscales and Question 2 of the Questionnaire were subjected to analysis. Model contained treatment, visit and treatment by visit interaction as fixed effects and Baseline (predose in Study A3921030) as a covariate. A first-order autoregressive variance-covariance structure was used.

End point type

Secondary

End point timeframe

Months 24, 36

End point values	Cyclosporine (CsA)	Tofacitinib Less Intensive (LI)	Tofacitinib More Intensive (MI)
Number of subjects analysed	64	60	54
Units: Score on a scale
least squares mean (standard error)
Month 24 (n=41,33,24): Physical Functioning	49.04 ( 1.16 )	47 ( 1.29 )	45.47 ( 1.49 )
Month 24 (n=41,33,24): Role Physical	46.36 ( 1.41 )	47.72 ( 1.56 )	44.4 ( 1.82 )
Month 24 (n=41,33,24): Bodily Pain	51.37 ( 1.42 )	51.66 ( 1.58 )	51.47 ( 1.84 )
Month 24 (n=41,33,24): General Health	46.51 ( 1.19 )	48.25 ( 1.32 )	47.6 ( 1.54 )
Month 24 (n=41,33,24): Vitality	53.31 ( 1.25 )	53.27 ( 1.39 )	55.07 ( 1.64 )
Month 24 (n=41,33,24): Social Functioning	49.55 ( 1.33 )	49.41 ( 1.47 )	49.95 ( 1.74 )
Month 24 (n=41,33,24): Role Emotional	44.65 ( 1.55 )	48.47 ( 1.72 )	44.17 ( 2.01 )
Month 24 (n=41,33,24): Mental Health	49.52 ( 1.35 )	47.83 ( 1.5 )	53.08 ( 1.76 )
Month 24 (n=41,33,24): TR Scale Score	2.63 ( 0.1 )	2.85 ( 0.12 )	2.86 ( 0.14 )
Month 24 (n=41,33,24): Physical Component Summary	49 ( 1.13 )	48.99 ( 1.25 )	46.57 ( 1.45 )
Month 24 (n=41,33,24): Mental Component Summary	48.65 ( 1.29 )	49.62 ( 1.43 )	51.92 ( 1.68 )
Month 36 (n=35,21,10): Physical Functioning	48.62 ( 1.25 )	46.97 ( 1.6 )	46.18 ( 2.27 )
Month 36 (n=35,21,10): Role Physical	48 ( 1.52 )	48.52 ( 1.94 )	46 ( 2.79 )
Month 36 (n=35,21,10): Bodily Pain	50.57 ( 1.54 )	52.66 ( 1.97 )	50.19 ( 2.84 )
Month 36 (n=35,21,10): General Health	46.06 ( 1.29 )	47.83 ( 1.63 )	47.02 ( 2.32 )
Month 36 (n=35,21,10): Vitality	53.01 ( 1.35 )	54.45 ( 1.73 )	57.43 ( 2.5 )
Month 36 (n=35,21,10): Social Functioning	48.96 ( 1.44 )	51.43 ( 1.84 )	48.33 ( 2.65 )
Month 36 (n=35,21,10): Role Emotional	46.35 ( 1.68 )	51.97 ( 2.15 )	47.58 ( 3.09 )
Month 36 (n=35,21,10): Mental health	50.21 ( 1.46 )	51.84 ( 1.86 )	50.59 ( 2.68 )
Month 36 (n=35,21,10): TR Scale Score	2.46 ( 0.11 )	2.65 ( 0.14 )	2.83 ( 0.21 )
Month 36 (n=35,21,10): Physical Component Summary	48.55 ( 1.22 )	48 ( 1.55 )	47.07 ( 2.21 )
Month 36 (n=35,21,10): Mental Component Summary	49.45 ( 1.39 )	53.5 ( 1.77 )	52.32 ( 2.55 )

LS Means of SF-36 V2 Component and Domain Scores

Statistical analysis description

Month 24: Physical Functioning

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[340]

P-value

= 0.2393

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-2.04

Confidence interval

level

95%

sides

2-sided

lower limit

-5.45

upper limit

1.36

Variability estimate

Standard error of the mean

Dispersion value

1.73

Notes
[340] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of SF-36 V2 Component and Domain Scores

Statistical analysis description

Month 24: Physical Functioning

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[341]

P-value

= 0.0595

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-3.57

Confidence interval

level

95%

sides

2-sided

lower limit

-7.29

upper limit

0.14

Variability estimate

Standard error of the mean

Dispersion value

1.89

Notes
[341] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of SF-36 V2 Component and Domain Scores

Statistical analysis description

Month 24: Role Physical

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[342]

P-value

= 0.5182

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

1.36

Confidence interval

level

95%

sides

2-sided

lower limit

-2.77

upper limit

5.49

Variability estimate

Standard error of the mean

Dispersion value

2.1

Notes
[342] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of SF-36 V2 Component and Domain Scores

Statistical analysis description

Month 24: Role Physical

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[343]

P-value

= 0.3938

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-1.96

Confidence interval

level

95%

sides

2-sided

lower limit

-6.49

upper limit

2.56

Variability estimate

Standard error of the mean

Dispersion value

2.3

Notes
[343] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of SF-36 V2 Component and Domain Scores

Statistical analysis description

Month 24: Bodily Pain

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[344]

P-value

= 0.8932

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

0.29

Confidence interval

level

95%

sides

2-sided

lower limit

-3.89

upper limit

4.46

Variability estimate

Standard error of the mean

Dispersion value

2.12

Notes
[344] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of SF-36 V2 Component and Domain Scores

Statistical analysis description

Month 24: Bodily Pain

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[345]

P-value

= 0.9673

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

0.1

Confidence interval

level

95%

sides

2-sided

lower limit

-4.48

upper limit

4.67

Variability estimate

Standard error of the mean

Dispersion value

2.33

Notes
[345] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of SF-36 V2 Component and Domain Scores

Statistical analysis description

Month 24: General Health

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[346]

P-value

= 0.329

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

1.74

Confidence interval

level

95%

sides

2-sided

lower limit

-1.76

upper limit

5.23

Variability estimate

Standard error of the mean

Dispersion value

1.78

Notes
[346] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of SF-36 V2 Component and Domain Scores

Statistical analysis description

Month 24: General Health

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[347]

P-value

= 0.578

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

1.09

Confidence interval

level

95%

sides

2-sided

lower limit

-2.75

upper limit

4.92

Variability estimate

Standard error of the mean

Dispersion value

1.95

Notes
[347] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of SF36 V2 Component and Domain Scores

Statistical analysis description

Month 24: Vitality

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[348]

P-value

= 0.9799

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.05

Confidence interval

level

95%

sides

2-sided

lower limit

-3.72

upper limit

3.62

Variability estimate

Standard error of the mean

Dispersion value

1.87

Notes
[348] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS means of SF-36 V2 Component and Domain Scores

Statistical analysis description

Month 24: Vitality

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[349]

P-value

= 0.396

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

1.76

Confidence interval

level

95%

sides

2-sided

lower limit

-2.31

upper limit

5.83

Variability estimate

Standard error of the mean

Dispersion value

2.07

Notes
[349] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of SF-36 V2 Component and Domain Scores

Statistical analysis description

Month 24: Social Functioning

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[350]

P-value

= 0.94

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.15

Confidence interval

level

95%

sides

2-sided

lower limit

-4.05

upper limit

3.75

Variability estimate

Standard error of the mean

Dispersion value

1.98

Notes
[350] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of SF-36 V2 Component and Domain Scores

Statistical analysis description

Month 24: Social Functioning

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[351]

P-value

= 0.8583

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

0.39

Confidence interval

level

95%

sides

2-sided

lower limit

-3.94

upper limit

4.72

Variability estimate

Standard error of the mean

Dispersion value

2.2

Notes
[351] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of SF-36 V2 Component and Domain Scores

Statistical analysis description

Month 24: Role Emotional

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[352]

P-value

= 0.0997

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

3.82

Confidence interval

level

95%

sides

2-sided

lower limit

-0.73

upper limit

8.37

Variability estimate

Standard error of the mean

Dispersion value

2.31

Notes
[352] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of SF-36 V2 Component and Domain Scores

Statistical analysis description

Month 24: Role Emotional

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[353]

P-value

= 0.852

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.47

Confidence interval

level

95%

sides

2-sided

lower limit

-5.47

upper limit

4.52

Variability estimate

Standard error of the mean

Dispersion value

2.54

Notes
[353] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of SF-36 V2 Component and Domain Scores

Statistical analysis description

Month 24: Mental Health

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[354]

P-value

= 0.4023

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-1.69

Confidence interval

level

95%

sides

2-sided

lower limit

-5.64

upper limit

2.27

Variability estimate

Standard error of the mean

Dispersion value

2.01

Notes
[354] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of SF-36 V2 Component and Domain Scores

Statistical analysis description

Month 24: Mental Health

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[355]

P-value

= 0.1092

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

3.56

Confidence interval

level

95%

sides

2-sided

lower limit

-0.8

upper limit

7.92

Variability estimate

Standard error of the mean

Dispersion value

2.22

Notes
[355] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of SF-36 V2 Component and Domain Scores

Statistical analysis description

Month 24: TR Scale Score

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[356]

P-value

= 0.1754

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

0.21

Confidence interval

level

95%

sides

2-sided

lower limit

-0.1

upper limit

0.52

Variability estimate

Standard error of the mean

Dispersion value

0.16

Notes
[356] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS means of SF-36 V2 Component and Domain Scores

Statistical analysis description

Month 24: TR Scale Score

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[357]

P-value

= 0.1802

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

0.23

Confidence interval

level

95%

sides

2-sided

lower limit

-0.11

upper limit

0.57

Variability estimate

Standard error of the mean

Dispersion value

0.17

Notes
[357] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of SF-36 V2 Component and Domain Scores

Statistical analysis description

Month 24: Physical Component Summary

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[358]

P-value

= 0.9966

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.01

Confidence interval

level

95%

sides

2-sided

lower limit

-3.31

upper limit

3.29

Variability estimate

Standard error of the mean

Dispersion value

1.68

Notes
[358] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS means of SF-36 V2 Component and Domain Scores

Statistical analysis description

Month 24: Physical Component Summary

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[359]

P-value

= 0.188

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-2.42

Confidence interval

level

95%

sides

2-sided

lower limit

-6.04

upper limit

1.19

Variability estimate

Standard error of the mean

Dispersion value

1.84

Notes
[359] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of SF-36 V2 Component and Domain Scores

Statistical analysis description

Month 24: Mental Component Summary

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[360]

P-value

= 0.6154

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

0.96

Confidence interval

level

95%

sides

2-sided

lower limit

-2.81

upper limit

4.73

Variability estimate

Standard error of the mean

Dispersion value

1.92

Notes
[360] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of SF-36 V2 Component and Domain Scores

Statistical analysis description

Month 24: Mental Component Summary

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[361]

P-value

= 0.1248

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

3.26

Confidence interval

level

95%

sides

2-sided

lower limit

-0.91

upper limit

7.43

Variability estimate

Standard error of the mean

Dispersion value

2.12

Notes
[361] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of SF-36 V2 Component and Domain Scores

Statistical analysis description

Month 36: Physical Functioning

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[362]

P-value

= 0.4174

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-1.65

Confidence interval

level

95%

sides

2-sided

lower limit

-5.63

upper limit

2.34

Variability estimate

Standard error of the mean

Dispersion value

2.03

Notes
[362] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of SF-36 V2 Component and Domain Scores

Statistical analysis description

Month 36: Physical Functioning

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[363]

P-value

= 0.3486

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-2.44

Confidence interval

level

95%

sides

2-sided

lower limit

-7.54

upper limit

2.66

Variability estimate

Standard error of the mean

Dispersion value

2.6

Notes
[363] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of SF-36 V2 Component and Domain Scores

Statistical analysis description

Month 36: Role Physical

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[364]

P-value

= 0.8335

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

0.52

Confidence interval

level

95%

sides

2-sided

lower limit

-4.33

upper limit

5.37

Variability estimate

Standard error of the mean

Dispersion value

2.47

Notes
[364] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of SF-36 V2 Component and Domain Scores

Statistical analysis description

Month 36: Role Physical

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[365]

P-value

= 0.5291

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-2

Confidence interval

level

95%

sides

2-sided

lower limit

-8.24

upper limit

4.24

Variability estimate

Standard error of the mean

Dispersion value

3.18

Notes
[365] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of SF-36 V2 Component and Domain Scores

Statistical analysis description

Month 36: Bodily Pain

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[366]

P-value

= 0.4033

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

2.09

Confidence interval

level

95%

sides

2-sided

lower limit

-2.82

upper limit

Variability estimate

Standard error of the mean

Dispersion value

2.5

Notes
[366] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of SF-36 V2 Component and Domain Scores

Statistical analysis description

Month 36: Bodily Pain

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[367]

P-value

= 0.9078

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.38

Confidence interval

level

95%

sides

2-sided

lower limit

-6.74

upper limit

5.99

Variability estimate

Standard error of the mean

Dispersion value

3.24

Notes
[367] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of SF-36 V2 Component and Domain Scores

Statistical analysis description

Month 36: General Health

Comparison groups

Tofacitinib Less Intensive (LI) v Cyclosporine (CsA)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[368]

P-value

= 0.3947

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

1.77

Confidence interval

level

95%

sides

2-sided

lower limit

-2.31

upper limit

5.86

Variability estimate

Standard error of the mean

Dispersion value

2.08

Notes
[368] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of SF-36 V2 Component and Domain Scores

Statistical analysis description

Month 36: General Health

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[369]

P-value

= 0.7165

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

0.97

Confidence interval

level

95%

sides

2-sided

lower limit

-4.26

upper limit

6.2

Variability estimate

Standard error of the mean

Dispersion value

2.66

Notes
[369] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of SF-36 V2 Component and Domain Scores

Statistical analysis description

Month 36: Vitality

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[370]

P-value

= 0.5112

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

1.44

Confidence interval

level

95%

sides

2-sided

lower limit

-2.87

upper limit

5.75

Variability estimate

Standard error of the mean

Dispersion value

2.19

Notes
[370] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of SF-36 V2 Component and Domain Scores

Statistical analysis description

Month 36: Vitality

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[371]

P-value

= 0.1218

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

4.43

Confidence interval

level

95%

sides

2-sided

lower limit

-1.18

upper limit

10.04

Variability estimate

Standard error of the mean

Dispersion value

2.86

Notes
[371] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of SF-36 V2 Component and Domain Scores

Statistical analysis description

Month 36: Social Functioning

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[372]

P-value

= 0.2895

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

2.47

Confidence interval

level

95%

sides

2-sided

lower limit

-2.11

upper limit

7.05

Variability estimate

Standard error of the mean

Dispersion value

2.33

Notes
[372] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of SF-36 V2 Component and Domain Scores

Statistical analysis description

Month 36: Social Functioning

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[373]

P-value

= 0.8349

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.63

Confidence interval

level

95%

sides

2-sided

lower limit

-6.58

upper limit

5.32

Variability estimate

Standard error of the mean

Dispersion value

3.03

Notes
[373] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of SF-36 V2 Component and Domain Scores

Statistical analysis description

Month 36: Role Emotional

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[374]

P-value

= 0.0393

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

5.62

Confidence interval

level

95%

sides

2-sided

lower limit

0.28

upper limit

10.97

Variability estimate

Standard error of the mean

Dispersion value

2.72

Notes
[374] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of SF-36 V2 Component and Domain Scores

Statistical analysis description

Month 36: Role Emotional

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[375]

P-value

= 0.7266

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

1.23

Confidence interval

level

95%

sides

2-sided

lower limit

-5.69

upper limit

8.16

Variability estimate

Standard error of the mean

Dispersion value

3.52

Notes
[375] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of SF-36 V2 Component and Domain Scores

Statistical analysis description

Month 36: Mental Health

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[376]

P-value

= 0.4916

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

1.63

Confidence interval

level

95%

sides

2-sided

lower limit

-3.02

upper limit

6.27

Variability estimate

Standard error of the mean

Dispersion value

2.36

Notes
[376] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of SF-36 V2 Component and Domain Scores

Statistical analysis description

Month 36: Mental Health

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[377]

P-value

= 0.9008

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

0.38

Confidence interval

level

95%

sides

2-sided

lower limit

-5.62

upper limit

6.38

Variability estimate

Standard error of the mean

Dispersion value

3.05

Notes
[377] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS means of SF-36 V2 Component and Domain Scores

Statistical analysis description

Month 36: TR Scale Score

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[378]

P-value

= 0.2965

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

0.19

Confidence interval

level

95%

sides

2-sided

lower limit

-0.17

upper limit

0.55

Variability estimate

Standard error of the mean

Dispersion value

0.18

Notes
[378] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of SF-36 V2 Component and Domain Scores

Statistical analysis description

Month 36: TR Scale Score

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[379]

P-value

= 0.1147

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

0.37

Confidence interval

level

95%

sides

2-sided

lower limit

-0.09

upper limit

0.84

Variability estimate

Standard error of the mean

Dispersion value

0.24

Notes
[379] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of SF-36 V2 Component and Domain Scores

Statistical analysis description

Month 36: Physical Component Summary

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[380]

P-value

= 0.7786

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.55

Confidence interval

level

95%

sides

2-sided

lower limit

-4.42

upper limit

3.31

Variability estimate

Standard error of the mean

Dispersion value

1.97

Notes
[380] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of SF-36 V2 Component and Domain Scores

Statistical analysis description

Month 36: Physical Component Summary

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[381]

P-value

= 0.5582

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-1.48

Confidence interval

level

95%

sides

2-sided

lower limit

-6.45

upper limit

3.49

Variability estimate

Standard error of the mean

Dispersion value

2.53

Notes
[381] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of SF-36 V2 Component and Domain Scores

Statistical analysis description

Month 36: Mental Component Summary

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[382]

P-value

= 0.0727

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

4.05

Confidence interval

level

95%

sides

2-sided

lower limit

-0.37

upper limit

8.47

Variability estimate

Standard error of the mean

Dispersion value

2.25

Notes
[382] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of SF-36 V2 Component and Domain Scores

Statistical analysis description

Month 36: Mental Component Summary

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[383]

P-value

= 0.3264

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

2.86

Confidence interval

level

95%

sides

2-sided

lower limit

-2.86

upper limit

8.59

Variability estimate

Standard error of the mean

Dispersion value

2.91

Notes
[383] - 'Standard error of the mean' refers to 'standard error of the mean difference'

Secondary: LS Means of End-Stage Renal Disease (ESRD) Symptom Checklist (SCL) -Transplantation Modules at Months 24 and 36

Top of page

End point title

LS Means of End-Stage Renal Disease (ESRD) Symptom Checklist (SCL) -Transplantation Modules at Months 24 and 36

End point description

ESRD-SCL: a 43-item disease specific self-administered questionnaire. Participants’ rated the question “At the moment,how much do you suffer?” for each item on a 5 point scale, range (Ra) from 0 (not at all) to 4 (extremely). Consisted of 6 subscales: Cardiac and Renal (CR) dysfunction; Ra 0 to 28, Increased(In) Growth of Gum and Hair (IGGH); Ra 0 to 20, Limited Cognitive Capacity (LCC); Ra 0 to 32, Limited Physical Capacity (LPC); Ra 0 to 40, Side Effects (SEs) of Corticosteroids; Ra 0 to 20, Transplantation Associated Psychological Distress (TAPD); Ra 0 to 32. Total Score: 0 to 172, higher scores indicate greater dysfunction. Model contained treatment, visit and treatment by visit interaction as fixed effects and Baseline (predose in Study A3921030) as a covariate. A first-order autoregressive variance-covariance structure was used.

End point type

Secondary

End point timeframe

Months 24, 36

End point values	Cyclosporine (CsA)	Tofacitinib Less Intensive (LI)	Tofacitinib More Intensive (MI)
Number of subjects analysed	64	60	54
Units: Score on a scale
least squares mean (standard error)
Month 24 Limited Physical Capacity (n=40,33,23)	0.59 ( 0.07 )	0.7 ( 0.08 )	0.71 ( 0.1 )
Month 24 Limited Cognitive Capacity (n=40,34,23)	0.63 ( 0.08 )	0.71 ( 0.08 )	0.75 ( 0.1 )
Month 24 CR Dysfunction (n=40,33,23)	0.63 ( 0.07 )	0.58 ( 0.08 )	0.53 ( 0.1 )
Month 24 SE of Corticosteroids (40, 33, 23)	0.42 ( 0.08 )	0.57 ( 0.09 )	0.6 ( 0.11 )
Month 24 IGGH (n=40,33,23)	0.54 ( 0.07 )	0.19 ( 0.08 )	0.17 ( 0.09 )
Month 24 TAPD (n=40,34,23)	0.61 ( 0.08 )	0.77 ( 0.09 )	0.63 ( 0.11 )
Month 24 Global Score (n=40,33,23)	0.58 ( 0.06 )	0.62 ( 0.06 )	0.59 ( 0.07 )
Month 36 Limited Physical Capacity (n=33,21,8)	0.71 ( 0.08 )	0.69 ( 0.1 )	0.88 ( 0.16 )
Month 36 Limited Cognitive Capacity (n=34,21,8)	0.67 ( 0.08 )	0.73 ( 0.1 )	0.85 ( 0.17 )
Month 36 Cardiac and Renal Dysfunction (n=33,21,8)	0.58 ( 0.08 )	0.57 ( 0.1 )	0.76 ( 0.16 )
Month 36 SE of Corticosteroids (n=33,21,8)	0.44 ( 0.09 )	0.39 ( 0.11 )	0.58 ( 0.18 )
Month 36 IGGH (n=33,20,8)	0.54 ( 0.08 )	0.33 ( 0.1 )	0.23 ( 0.15 )
Month 36 TAPD (n=34,21,8)	0.77 ( 0.09 )	0.82 ( 0.11 )	0.68 ( 0.18 )
Month 36 Global Score (n=33,21,8)	0.64 ( 0.06 )	0.63 ( 0.08 )	0.7 ( 0.12 )

LS Means of ESRD SCL Transplantation Modules

Statistical analysis description

Month 24 Limited Physical Capacity

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[384]

P-value

= 0.3093

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

0.11

Confidence interval

level

95%

sides

2-sided

lower limit

-0.1

upper limit

0.33

Variability estimate

Standard error of the mean

Dispersion value

0.11

Notes
[384] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of ESRD SCL Transplantation Modules

Statistical analysis description

Month 24 Limited Physical Capacity

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[385]

P-value

= 0.3223

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

0.12

Confidence interval

level

95%

sides

2-sided

lower limit

-0.12

upper limit

0.36

Variability estimate

Standard error of the mean

Dispersion value

0.12

Notes
[385] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of ESRD SCL Transplantation Modules

Statistical analysis description

Month 24 Limited Cognitive Capacity

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[386]

P-value

= 0.4858

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

0.08

Confidence interval

level

95%

sides

2-sided

lower limit

-0.14

upper limit

0.3

Variability estimate

Standard error of the mean

Dispersion value

0.11

Notes
[386] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of ESRD SCL Transplantation Modules

Statistical analysis description

Month 24 Limited Cognitive Capacity

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[387]

P-value

= 0.3679

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

0.11

Confidence interval

level

95%

sides

2-sided

lower limit

-0.13

upper limit

0.36

Variability estimate

Standard error of the mean

Dispersion value

0.13

Notes
[387] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of ESRD SCL Transplantation Modules

Statistical analysis description

Month 24 Cardiac and Renal Dysfunction

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[388]

P-value

= 0.6416

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.05

Confidence interval

level

95%

sides

2-sided

lower limit

-0.27

upper limit

0.17

Variability estimate

Standard error of the mean

Dispersion value

0.11

Notes
[388] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of ESRD SCL Transplantation Modules

Statistical analysis description

Month 24 Cardiac and Renal Dysfunction

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[389]

P-value

= 0.4241

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.1

Confidence interval

level

95%

sides

2-sided

lower limit

-0.34

upper limit

0.14

Variability estimate

Standard error of the mean

Dispersion value

0.12

Notes
[389] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of ESRD SCL Transplantation Modules

Statistical analysis description

Month 24 Side Effects of Corticosteroids

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[390]

P-value

= 0.2133

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

0.15

Confidence interval

level

95%

sides

2-sided

lower limit

-0.09

upper limit

0.39

Variability estimate

Standard error of the mean

Dispersion value

0.12

Notes
[390] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of ESRD SCL Transplantation Modules

Statistical analysis description

Month 24 Side Effects of Corticosteroids

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[391]

P-value

= 0.1918

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

0.17

Confidence interval

level

95%

sides

2-sided

lower limit

-0.09

upper limit

0.44

Variability estimate

Standard error of the mean

Dispersion value

0.13

Notes
[391] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of ESRD SCL Transplantation Modules

Statistical analysis description

Month 24 Increased Growth of Gum and Hair

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[392]

P-value

= 0.001

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.35

Confidence interval

level

95%

sides

2-sided

lower limit

-0.55

upper limit

-0.14

Variability estimate

Standard error of the mean

Dispersion value

0.1

Notes
[392] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of ESRD SCL Transplantation Modules

Statistical analysis description

Month 24 Increased Growth of Gum and Hair

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[393]

P-value

= 0.002

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.36

Confidence interval

level

95%

sides

2-sided

lower limit

-0.59

upper limit

-0.13

Variability estimate

Standard error of the mean

Dispersion value

0.12

Notes
[393] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of ESRD SCL Transplantation Modules

Statistical analysis description

Month 24 Transplantation-Associated Psychological Distress

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[394]

P-value

= 0.2012

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

0.16

Confidence interval

level

95%

sides

2-sided

lower limit

-0.08

upper limit

0.4

Variability estimate

Standard error of the mean

Dispersion value

0.12

Notes
[394] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of ESRD SCL Transplantation Modules

Statistical analysis description

Month 24 Transplantation-Associated Psychological Distress

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[395]

P-value

= 0.8986

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

0.02

Confidence interval

level

95%

sides

2-sided

lower limit

-0.25

upper limit

0.29

Variability estimate

Standard error of the mean

Dispersion value

0.14

Notes
[395] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of ESRD SCL Transplantation Modules

Statistical analysis description

Month 24 Global Score

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[396]

P-value

= 0.6724

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

0.04

Confidence interval

level

95%

sides

2-sided

lower limit

-0.13

upper limit

0.2

Variability estimate

Standard error of the mean

Dispersion value

0.08

Notes
[396] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of ESRD SCL Transplantation Modules

Statistical analysis description

Month 24 Global Score

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[397]

P-value

= 0.9297

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

0.01

Confidence interval

level

95%

sides

2-sided

lower limit

-0.18

upper limit

0.19

Variability estimate

Standard error of the mean

Dispersion value

0.09

Notes
[397] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of ESRD SCL Transplantation Modules

Statistical analysis description

Month 36 Limited Physical Capacity

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[398]

P-value

= 0.8682

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.02

Confidence interval

level

95%

sides

2-sided

lower limit

-0.28

upper limit

0.23

Variability estimate

Standard error of the mean

Dispersion value

0.13

Notes
[398] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of ESRD SCL Transplantation Modules

Statistical analysis description

Month 36 Limited Physical Capacity

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[399]

P-value

= 0.3392

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

0.17

Confidence interval

level

95%

sides

2-sided

lower limit

-0.18

upper limit

0.53

Variability estimate

Standard error of the mean

Dispersion value

0.18

Notes
[399] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of ESRD SCL Transplantation Modules

Statistical analysis description

Month 36 Limited Cognitive Capacity

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[400]

P-value

= 0.6545

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

0.06

Confidence interval

level

95%

sides

2-sided

lower limit

-0.2

upper limit

0.32

Variability estimate

Standard error of the mean

Dispersion value

0.13

Notes
[400] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of ESRD SCL Transplantation Modules

Statistical analysis description

Month 36 Limited Cognitive Capacity

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[401]

P-value

= 0.3253

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

0.18

Confidence interval

level

95%

sides

2-sided

lower limit

-0.18

upper limit

0.55

Variability estimate

Standard error of the mean

Dispersion value

0.19

Notes
[401] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS means of ESRD SCL Transplantation Modules

Statistical analysis description

Month 36 Cardiac and Renal Dysfunction

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[402]

P-value

= 0.9698

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-0.26

upper limit

0.25

Variability estimate

Standard error of the mean

Dispersion value

0.13

Notes
[402] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of ESRD SCL Transplantation Modules

Statistical analysis description

Month 36 Cardiac and Renal Dysfunction

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[403]

P-value

= 0.3065

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

0.19

Confidence interval

level

95%

sides

2-sided

lower limit

-0.17

upper limit

0.54

Variability estimate

Standard error of the mean

Dispersion value

0.18

Notes
[403] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS means of ESRD SCL Transplantation Modules

Statistical analysis description

Month 36 Side Effects of Corticosteroids

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[404]

P-value

= 0.7147

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.05

Confidence interval

level

95%

sides

2-sided

lower limit

-0.33

upper limit

0.23

Variability estimate

Standard error of the mean

Dispersion value

0.14

Notes
[404] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of ESRD SCL Transplantation Modules

Statistical analysis description

Month 36 Side Effects of Corticosteroids

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[405]

P-value

= 0.4852

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

0.14

Confidence interval

level

95%

sides

2-sided

lower limit

-0.25

upper limit

0.53

Variability estimate

Standard error of the mean

Dispersion value

0.2

Notes
[405] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of ESRD SCL Transplantation Modules

Statistical analysis description

Month 36 Increased Growth of Gum and Hair

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[406]

P-value

= 0.0888

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.21

Confidence interval

level

95%

sides

2-sided

lower limit

-0.46

upper limit

0.03

Variability estimate

Standard error of the mean

Dispersion value

0.13

Notes
[406] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of ESRD SCL Transplantation Modules

Statistical analysis description

Month 36 Increased Growth of Gum and Hair

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[407]

P-value

= 0.0719

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.31

Confidence interval

level

95%

sides

2-sided

lower limit

-0.65

upper limit

0.03

Variability estimate

Standard error of the mean

Dispersion value

0.17

Notes
[407] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of ESRD SCL Transplantation Modules

Statistical analysis description

Month 36 Transplantation-Associated Psychological Distress

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[408]

P-value

= 0.7531

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

0.05

Confidence interval

level

95%

sides

2-sided

lower limit

-0.24

upper limit

0.33

Variability estimate

Standard error of the mean

Dispersion value

0.14

Notes
[408] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of ESRD SCL Transplantation Modules

Statistical analysis description

Month 36 Transplantation-Associated Psychological Distress

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[409]

P-value

= 0.6412

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.09

Confidence interval

level

95%

sides

2-sided

lower limit

-0.49

upper limit

0.3

Variability estimate

Standard error of the mean

Dispersion value

0.2

Notes
[409] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of ESRD SCL Transplantation Modules

Statistical analysis description

Month 36 Global Score

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[410]

P-value

= 0.9186

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.01

Confidence interval

level

95%

sides

2-sided

lower limit

-0.2

upper limit

0.18

Variability estimate

Standard error of the mean

Dispersion value

0.1

Notes
[410] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of ESRD SCL Transplantation Modules

Statistical analysis description

Month 36 Global Score

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[411]

P-value

= 0.6629

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

0.06

Confidence interval

level

95%

sides

2-sided

lower limit

-0.21

upper limit

0.33

Variability estimate

Standard error of the mean

Dispersion value

0.14

Notes
[411] - 'Standard error of the mean' refers to 'standard error of the mean difference'

Secondary: LSMeans of Severity of Dyspepsia Assessment (SODA) Subscales at Months 24 & 36

Top of page

End point title

LSMeans of Severity of Dyspepsia Assessment (SODA) Subscales at Months 24 & 36

End point description

SODA:17-item health scale, assessed participant-reported perceptions of dyspepsia; consists of 3 subscales: Pain Intensity (PI, 6-items to assess pain and intensity of abdominal discomfort; Range: 2 to 47, higher score indicates greater pain and abdominal discomfort), Non-Pain Symptoms (NPS, 7-items to assess severity and impact of non-pain symptoms: burping/belching, heartburn, bloating, flatulence, sour taste, nausea, and bad breath; Range: 7 to 35, higher scores indicate increased symptom severity and influence), and Satisfaction (4-items to assess degree of satisfaction with abdominal discomfort; Range: 2 to 23, higher scores indicate more satisfaction). Model contained treatment, visit and treatment by visit interaction as fixed effects and Baseline (predose in Study A3921030) as a covariate. A first-order autoregressive variance-covariance structure was used.

End point type

Secondary

End point timeframe

Months 24, 36

End point values	Cyclosporine (CsA)	Tofacitinib Less Intensive (LI)	Tofacitinib More Intensive (MI)
Number of subjects analysed	64	60	54
Units: Score
least squares mean (standard error)
Month 24 PI Total Converted Score (n=46,39,24)	9.51 ( 1.16 )	7.66 ( 1.26 )	10.73 ( 1.59 )
Month 24 NPS Converted Score (n=49,41,25)	11.44 ( 0.42 )	11.24 ( 0.46 )	12.25 ( 0.58 )
Month 24 Satisfaction Converted Score (n=49,41,24)	17.22 ( 0.66 )	18.11 ( 0.72 )	16.33 ( 0.94 )
Month 36 PI Total Converted Score (n=40,27,10)	9.63 ( 1.25 )	8.03 ( 1.51 )	10.59 ( 2.45 )
Month 36 NPS Converted Score (n=42,28,10)	11.31 ( 0.45 )	11.14 ( 0.55 )	12.44 ( 0.91 )
Month 36 Satisfaction Converted Score (n=42,28,10)	17.44 ( 0.72 )	17.9 ( 0.87 )	16.31 ( 1.45 )

LS Means of SODA Subscales

Statistical analysis description

Month 24 Pain Intensity Total Converted Score

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[412]

P-value

= 0.2826

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-1.85

Confidence interval

level

95%

sides

2-sided

lower limit

-5.22

upper limit

1.53

Variability estimate

Standard error of the mean

Dispersion value

1.72

Notes
[412] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of SODA Subscales

Statistical analysis description

Month 24 Pain Intensity Total Converted Score

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[413]

P-value

= 0.5371

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

1.22

Confidence interval

level

95%

sides

2-sided

lower limit

-2.65

upper limit

5.09

Variability estimate

Standard error of the mean

Dispersion value

1.97

Notes
[413] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of SODA Subscales

Statistical analysis description

Month 24 Non-Pain Symptoms Converted Score

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[414]

P-value

= 0.7503

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.2

Confidence interval

level

95%

sides

2-sided

lower limit

-1.41

upper limit

1.02

Variability estimate

Standard error of the mean

Dispersion value

0.62

Notes
[414] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of SODA Subscales

Statistical analysis description

Month 24 Non-Pain Symptoms Converted Score

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[415]

P-value

= 0.261

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

0.81

Confidence interval

level

95%

sides

2-sided

lower limit

-0.6

upper limit

2.21

Variability estimate

Standard error of the mean

Dispersion value

0.72

Notes
[415] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of SODA Subscales

Statistical analysis description

Month 24 Satisfaction Converted Score

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[416]

P-value

= 0.3656

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

0.89

Confidence interval

level

95%

sides

2-sided

lower limit

-1.04

upper limit

2.82

Variability estimate

Standard error of the mean

Dispersion value

0.98

Notes
[416] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of SODA Subscales

Statistical analysis description

Month 24 Satisfaction Converted Score

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[417]

P-value

= 0.4405

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.89

Confidence interval

level

95%

sides

2-sided

lower limit

-3.16

upper limit

1.37

Variability estimate

Standard error of the mean

Dispersion value

1.15

Notes
[417] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of SODA Subscales

Statistical analysis description

Month 36 Pain Intensity Total Converted Score

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[418]

P-value

= 0.4135

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-1.6

Confidence interval

level

95%

sides

2-sided

lower limit

-5.45

upper limit

2.25

Variability estimate

Standard error of the mean

Dispersion value

1.96

Notes
[418] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of SODA Subscales

Statistical analysis description

Month 36 Pain Intensity Total Converted Score

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[419]

P-value

= 0.7272

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

0.96

Confidence interval

level

95%

sides

2-sided

lower limit

-4.45

upper limit

6.37

Variability estimate

Standard error of the mean

Dispersion value

2.75

Notes
[419] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of SODA Subscales

Statistical analysis description

Month 36 Non-Pain symptoms Converted Score

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[420]

P-value

= 0.8111

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.17

Confidence interval

level

95%

sides

2-sided

lower limit

-1.56

upper limit

1.22

Variability estimate

Standard error of the mean

Dispersion value

0.71

Notes
[420] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of SODA Subscales

Statistical analysis description

Month 36 Non-Pain Symptoms Converted Score

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[421]

P-value

= 0.2636

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

1.14

Confidence interval

level

95%

sides

2-sided

lower limit

-0.86

upper limit

3.13

Variability estimate

Standard error of the mean

Dispersion value

1.02

Notes
[421] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of SODA Subscales

Statistical analysis description

Month 36 Satisfaction Converted Score

Comparison groups

Cyclosporine (CsA) v Tofacitinib Less Intensive (LI)

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority ^[422]

P-value

= 0.689

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

0.45

Confidence interval

level

95%

sides

2-sided

lower limit

-1.77

upper limit

2.67

Variability estimate

Standard error of the mean

Dispersion value

1.13

Notes
[422] - 'Standard error of the mean' refers to 'standard error of the mean difference'

LS Means of SODA Subscales

Statistical analysis description

Month 36 Satisfaction Converted Score

Comparison groups

Cyclosporine (CsA) v Tofacitinib More Intensive (MI)

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority ^[423]

P-value

= 0.4853

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-1.13

Confidence interval

level

95%

sides

2-sided

lower limit

-4.31

upper limit

2.05

Variability estimate

Standard error of the mean

Dispersion value

1.62

Notes
[423] - 'Standard error of the mean' refers to 'standard error of the mean difference'

Secondary: Mean Trough Levels of Tofacitinib by Visit

Top of page

End point title

Mean Trough Levels of Tofacitinib by Visit ^[424]

End point description

The dates and times were recorded for the 6 doses of tofacitinib administered before each scheduled PK sampling. The participant was instructed to follow a 12 hourly schedule for these 6 doses of tofacitinib, with each dose administered within 1 hour of the scheduled time. Trough samples were collected 0 to 10 minutes prior to the morning dose. 1 hour postdose samples were required within 10 minutes of the nominal time point. Samples taken at -2 hours predose and at time points >1 hour post dose were required within 30 minutes of the nominal time point.

End point type

Secondary

End point timeframe

Months 18 and 24 (-2 hours, predose, 1 hour, 2 hours), Month 30 (predose, 1 hour and 2 hours), Month 36 (predose, 1, 2, and 4 hours), Months 42, 48, 54, 60, 66, 72 (predose and 2 hours)

Notes
[424] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoint was defined for comparator and tofacitinb separately in the Sponsor agreed Endpoints list because the treatment groups had PK measures reported at different timepoints. All treatment groups in the baseline period arms are reported, but across 2 separate endpoints

End point values	Tofacitinib Less Intensive (LI)	Tofacitinib More Intensive (MI)
Number of subjects analysed	60	54
Units: ng/mL
arithmetic mean (standard deviation)
Month 18 Predose -2 hours (n=31,22)	13.2 ( 10.43 )	10.68 ( 6.86 )
Month 18 Predose (n=58,46)	12.45 ( 11.83 )	15.27 ( 24.14 )
Month 18 1 hour (n=58,45)	56.62 ( 32.96 )	56.58 ( 37.56 )
Month 18 2 hours (n=26,23)	59.55 ( 25.87 )	56.6 ( 28.85 )
Month 24 Predose -2 hours (n=18,15)	11.71 ( 11.77 )	8.95 ( 8.72 )
Month 24 Predose (n=50,32)	9.93 ( 14.5 )	7.42 ( 4.88 )
Month 24 1 hour (n=49,31)	44.06 ( 26.16 )	41.93 ( 27.27 )
Month 24 2 hours (n=28,15)	37.73 ( 14 )	34.15 ( 15.27 )
Month 30 Predose (n=35,21)	8.7 ( 8.53 )	6.89 ( 6.94 )
Month 30 1 hour (n=35,21)	39.15 ( 16.06 )	44.12 ( 19.99 )
Month 30 2 hours (n=34,19)	38.07 ( 11.42 )	37.16 ( 17.51 )
Month 36 Predose (n=31,15)	6.35 ( 4.68 )	8.33 ( 10.76 )
Month 36 1 hour (n=30,14)	46.09 ( 12.54 )	38.07 ( 14.06 )
Month 36 2 hours (n=30,15)	38.11 ( 14.41 )	31.76 ( 7.45 )
Month 36 4 hours (n=30,15)	24.03 ( 10.34 )	21.46 ( 4.33 )
Month 42 Predose (n=31,14)	11.42 ( 12.07 )	7 ( 5.34 )
Month 42 2 hours (n=30,12)	35.27 ( 15.57 )	34.33 ( 11.1 )
Month 48 Predose (n=32,14)	7.58 ( 6.94 )	13.78 ( 11.05 )
Month 48 2 hours (n=32,12)	38.46 ( 12.36 )	41.1 ( 12.35 )
Month 54 Predose (n=30,11)	7.86 ( 5.52 )	7.09 ( 6.45 )
Month 54 2 hours (n=30,10)	41.18 ( 12.25 )	48.03 ( 10.39 )
Month 60 Predose (n=23,10)	6.58 ( 3.82 )	7.31 ( 5.41 )
Month 60 2 hours (n=23,10)	39.43 ( 9.26 )	38.98 ( 13.33 )
Month 66 Predose (n=22,10)	7.53 ( 9.19 )	5.81 ( 6.03 )
Month 66 2 hours (n=21,10)	36.17 ( 12.74 )	41.12 ( 12.27 )
Month 72 Predose (n=16,8)	8.3 ( 7.22 )	5.37 ( 5.05 )
Month 72 2 hours (n=16,8)	38.55 ( 14.38 )	38.93 ( 13.19 )

No statistical analyses for this end point

Secondary: Mean Trough Levels of Cyclosporine by Visit

Top of page

End point title

Mean Trough Levels of Cyclosporine by Visit ^[425]

End point description

All CsA samples were taken predose (collected 0 to 10 minutes prior to the morning dose).

End point type

Secondary

End point timeframe

Predose: Months 18, 24, 36, 48, 60, 72

Notes
[425] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoint was defined for comparator and tofacitinb separately in the Sponsor agreed Endpoints list because the treatment groups had PK measures reported at different timepoints. All treatment groups in the baseline period arms are reported, but across 2 separate endpoints

End point values	Cyclosporine (CsA)
Number of subjects analysed	64
Units: ng/mL
arithmetic mean (standard deviation)
Month 18 (n=58)	113.88 ( 98.73 )
Month 24 (n=54)	89.52 ( 45.23 )
Month 36 (n=50)	101.1 ( 100.63 )
Month 48 (n=39)	88.54 ( 62.45 )
Month 60 (n=35)	95 ( 115.74 )
Month 72 (n=23)	135.3 ( 188.05 )

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

Adverse events recorded from the time the participant took at least one dose of study treatment through last participant visit. Serious adverse events were recorded from informed consent through and including 28 calendar days from last administration.

Adverse event reporting additional description

The same event may appear as both an AE and SAE. An event may be categorized as serious in 1 participant and non-serious in another, or 1 participant may have experienced both a serious and non-serious event during the study. The total number of deaths from AEs represents deaths from SAEs considered by the investigator as related to treatment.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

18.0

Reporting group title

Cyclosporine

Reporting group description

Reporting group title

Tofacitinib Less Intensive (LI)

Reporting group description

Reporting group title

Tofacitinib More Intensive (MI)

Reporting group description

Serious adverse events	Cyclosporine	Tofacitinib Less Intensive (LI)	Tofacitinib More Intensive (MI)
Total subjects affected by serious adverse events
subjects affected / exposed	40 / 64 (62.50%)	32 / 60 (53.33%)	31 / 54 (57.41%)
number of deaths (all causes)	4	1	5
number of deaths resulting from adverse events	2	0	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma
subjects affected / exposed	0 / 64 (0.00%)	1 / 60 (1.67%)	1 / 54 (1.85%)
occurrences causally related to treatment / all	0 / 0	0 / 1	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Cervix carcinoma stage 0
subjects affected / exposed	0 / 64 (0.00%)	0 / 60 (0.00%)	1 / 54 (1.85%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Cholangiocarcinoma
subjects affected / exposed	1 / 64 (1.56%)	0 / 60 (0.00%)	0 / 54 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0
Clear cell renal cell carcinoma
subjects affected / exposed	1 / 64 (1.56%)	0 / 60 (0.00%)	0 / 54 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Lymphoma
subjects affected / exposed	0 / 64 (0.00%)	0 / 60 (0.00%)	1 / 54 (1.85%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Metastases to peritoneum
subjects affected / exposed	1 / 64 (1.56%)	0 / 60 (0.00%)	0 / 54 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0
Neuroendocrine carcinoma
subjects affected / exposed	1 / 64 (1.56%)	0 / 60 (0.00%)	0 / 54 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Non-Hodgkin's lymphoma
subjects affected / exposed	0 / 64 (0.00%)	0 / 60 (0.00%)	1 / 54 (1.85%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	1 / 1
Parathyroid tumour benign
subjects affected / exposed	1 / 64 (1.56%)	0 / 60 (0.00%)	0 / 54 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Prostate cancer
subjects affected / exposed	0 / 64 (0.00%)	0 / 60 (0.00%)	1 / 54 (1.85%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Renal cell carcinoma
subjects affected / exposed	0 / 64 (0.00%)	0 / 60 (0.00%)	1 / 54 (1.85%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Small intestine carcinoma
subjects affected / exposed	1 / 64 (1.56%)	0 / 60 (0.00%)	0 / 54 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Squamous cell carcinoma
subjects affected / exposed	0 / 64 (0.00%)	0 / 60 (0.00%)	1 / 54 (1.85%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Squamous cell carcinoma of skin
subjects affected / exposed	2 / 64 (3.13%)	1 / 60 (1.67%)	1 / 54 (1.85%)
occurrences causally related to treatment / all	2 / 2	1 / 1	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Vascular disorders
Aortic stenosis
subjects affected / exposed	0 / 64 (0.00%)	1 / 60 (1.67%)	0 / 54 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Arteriosclerosis
subjects affected / exposed	0 / 64 (0.00%)	0 / 60 (0.00%)	1 / 54 (1.85%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 1
Deep vein thrombosis
subjects affected / exposed	1 / 64 (1.56%)	1 / 60 (1.67%)	1 / 54 (1.85%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Extremity necrosis
subjects affected / exposed	0 / 64 (0.00%)	1 / 60 (1.67%)	0 / 54 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Hypertension
subjects affected / exposed	1 / 64 (1.56%)	0 / 60 (0.00%)	1 / 54 (1.85%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 1
Hypertensive crisis
subjects affected / exposed	1 / 64 (1.56%)	0 / 60 (0.00%)	0 / 54 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Hypotension
subjects affected / exposed	0 / 64 (0.00%)	0 / 60 (0.00%)	1 / 54 (1.85%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Hypovolaemic shock
subjects affected / exposed	1 / 64 (1.56%)	0 / 60 (0.00%)	0 / 54 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0
Intermittent claudication
subjects affected / exposed	0 / 64 (0.00%)	1 / 60 (1.67%)	0 / 54 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Peripheral ischaemia
subjects affected / exposed	0 / 64 (0.00%)	0 / 60 (0.00%)	1 / 54 (1.85%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Superior vena cava occlusion
subjects affected / exposed	0 / 64 (0.00%)	1 / 60 (1.67%)	0 / 54 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Thrombosis
subjects affected / exposed	0 / 64 (0.00%)	1 / 60 (1.67%)	0 / 54 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0
Pregnancy, puerperium and perinatal conditions
Unintended pregnancy
subjects affected / exposed	1 / 64 (1.56%)	0 / 60 (0.00%)	0 / 54 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
General disorders and administration site conditions
Chest Pain
subjects affected / exposed	3 / 64 (4.69%)	0 / 60 (0.00%)	1 / 54 (1.85%)
occurrences causally related to treatment / all	1 / 3	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Drug ineffective
subjects affected / exposed	1 / 64 (1.56%)	0 / 60 (0.00%)	0 / 54 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Impaired healing
subjects affected / exposed	0 / 64 (0.00%)	1 / 60 (1.67%)	0 / 54 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Oedema
subjects affected / exposed	1 / 64 (1.56%)	0 / 60 (0.00%)	0 / 54 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pyrexia
subjects affected / exposed	3 / 64 (4.69%)	1 / 60 (1.67%)	0 / 54 (0.00%)
occurrences causally related to treatment / all	0 / 3	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Immune system disorders
Kidney transplant rejection
subjects affected / exposed	2 / 64 (3.13%)	3 / 60 (5.00%)	2 / 54 (3.70%)
occurrences causally related to treatment / all	0 / 2	1 / 3	1 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 1
Transplant rejection
subjects affected / exposed	6 / 64 (9.38%)	2 / 60 (3.33%)	1 / 54 (1.85%)
occurrences causally related to treatment / all	4 / 7	1 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Acute pulmonary oedema
subjects affected / exposed	0 / 64 (0.00%)	1 / 60 (1.67%)	0 / 54 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Acute respiratory distress syndrome
subjects affected / exposed	1 / 64 (1.56%)	0 / 60 (0.00%)	0 / 54 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Asthma
subjects affected / exposed	0 / 64 (0.00%)	1 / 60 (1.67%)	0 / 54 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Dyspnoea
subjects affected / exposed	1 / 64 (1.56%)	0 / 60 (0.00%)	0 / 54 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Dyspnoea exertional
subjects affected / exposed	1 / 64 (1.56%)	0 / 60 (0.00%)	0 / 54 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Haemothorax
subjects affected / exposed	1 / 64 (1.56%)	0 / 60 (0.00%)	0 / 54 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0
Hypoxia
subjects affected / exposed	1 / 64 (1.56%)	0 / 60 (0.00%)	0 / 54 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pneumothorax
subjects affected / exposed	1 / 64 (1.56%)	0 / 60 (0.00%)	0 / 54 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pulmonary embolism
subjects affected / exposed	0 / 64 (0.00%)	0 / 60 (0.00%)	1 / 54 (1.85%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Respiratory distress
subjects affected / exposed	1 / 64 (1.56%)	0 / 60 (0.00%)	1 / 54 (1.85%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Respiratory failure
subjects affected / exposed	1 / 64 (1.56%)	0 / 60 (0.00%)	1 / 54 (1.85%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 1
deaths causally related to treatment / all	1 / 1	0 / 0	0 / 1
Vocal cord cyst
subjects affected / exposed	0 / 64 (0.00%)	1 / 60 (1.67%)	0 / 54 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Psychiatric disorders
Depression
subjects affected / exposed	0 / 64 (0.00%)	1 / 60 (1.67%)	1 / 54 (1.85%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Mental status changes
subjects affected / exposed	1 / 64 (1.56%)	0 / 60 (0.00%)	0 / 54 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0
Psychotic disorder
subjects affected / exposed	0 / 64 (0.00%)	1 / 60 (1.67%)	0 / 54 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Suicidal ideation
subjects affected / exposed	0 / 64 (0.00%)	0 / 60 (0.00%)	1 / 54 (1.85%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Investigations
Blood creatinine increased
subjects affected / exposed	1 / 64 (1.56%)	0 / 60 (0.00%)	2 / 54 (3.70%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Liver function test abnormal
subjects affected / exposed	1 / 64 (1.56%)	0 / 60 (0.00%)	0 / 54 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0
Injury, poisoning and procedural complications
Ankle fracture
subjects affected / exposed	1 / 64 (1.56%)	0 / 60 (0.00%)	0 / 54 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Arteriovenous fistula aneurysm
subjects affected / exposed	0 / 64 (0.00%)	0 / 60 (0.00%)	1 / 54 (1.85%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Arteriovenous fistula thrombosis
subjects affected / exposed	0 / 64 (0.00%)	1 / 60 (1.67%)	0 / 54 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Exposure during pregnancy
subjects affected / exposed	1 / 64 (1.56%)	0 / 60 (0.00%)	0 / 54 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Exposure via father
subjects affected / exposed	0 / 64 (0.00%)	1 / 60 (1.67%)	0 / 54 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Femoral neck fracture
subjects affected / exposed	0 / 64 (0.00%)	1 / 60 (1.67%)	0 / 54 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Incisional hernia
subjects affected / exposed	1 / 64 (1.56%)	0 / 60 (0.00%)	0 / 54 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Injury
subjects affected / exposed	0 / 64 (0.00%)	1 / 60 (1.67%)	0 / 54 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Lower limb fracture
subjects affected / exposed	0 / 64 (0.00%)	1 / 60 (1.67%)	0 / 54 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pelvic fracture
subjects affected / exposed	1 / 64 (1.56%)	0 / 60 (0.00%)	0 / 54 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Post procedural haematuria
subjects affected / exposed	1 / 64 (1.56%)	0 / 60 (0.00%)	0 / 54 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Renal transplant failure
subjects affected / exposed	0 / 64 (0.00%)	0 / 60 (0.00%)	1 / 54 (1.85%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Rib fracture
subjects affected / exposed	0 / 64 (0.00%)	0 / 60 (0.00%)	1 / 54 (1.85%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Toxicity to various agents
subjects affected / exposed	1 / 64 (1.56%)	0 / 60 (0.00%)	0 / 54 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Transplant dysfunction
subjects affected / exposed	1 / 64 (1.56%)	0 / 60 (0.00%)	0 / 54 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Transplant failure
subjects affected / exposed	0 / 64 (0.00%)	1 / 60 (1.67%)	0 / 54 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Urethral injury
subjects affected / exposed	0 / 64 (0.00%)	0 / 60 (0.00%)	1 / 54 (1.85%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Wound dehiscence
subjects affected / exposed	0 / 64 (0.00%)	0 / 60 (0.00%)	1 / 54 (1.85%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Congenital, familial and genetic disorders
Hydrocele
subjects affected / exposed	1 / 64 (1.56%)	0 / 60 (0.00%)	0 / 54 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Cardiac disorders
Angina pectoris
subjects affected / exposed	1 / 64 (1.56%)	0 / 60 (0.00%)	0 / 54 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Angina unstable
subjects affected / exposed	0 / 64 (0.00%)	1 / 60 (1.67%)	0 / 54 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Atrial fibrillation
subjects affected / exposed	0 / 64 (0.00%)	1 / 60 (1.67%)	0 / 54 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Atrial flutter
subjects affected / exposed	1 / 64 (1.56%)	0 / 60 (0.00%)	0 / 54 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0
Atrioventricular block
subjects affected / exposed	0 / 64 (0.00%)	1 / 60 (1.67%)	0 / 54 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Cardiac arrest
subjects affected / exposed	0 / 64 (0.00%)	0 / 60 (0.00%)	1 / 54 (1.85%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 1
Cardiac failure congestive
subjects affected / exposed	1 / 64 (1.56%)	0 / 60 (0.00%)	0 / 54 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Cardiopulmonary failure
subjects affected / exposed	0 / 64 (0.00%)	0 / 60 (0.00%)	1 / 54 (1.85%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 1
Coronary artery disease
subjects affected / exposed	0 / 64 (0.00%)	0 / 60 (0.00%)	2 / 54 (3.70%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 1
Coronary artery dissection
subjects affected / exposed	0 / 64 (0.00%)	0 / 60 (0.00%)	1 / 54 (1.85%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Coronary artery occlusion
subjects affected / exposed	1 / 64 (1.56%)	0 / 60 (0.00%)	0 / 54 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Coronary artery stenosis
subjects affected / exposed	1 / 64 (1.56%)	0 / 60 (0.00%)	0 / 54 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Myocardial infarction
subjects affected / exposed	2 / 64 (3.13%)	0 / 60 (0.00%)	1 / 54 (1.85%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 1
Nervous system disorders
Brain mass
subjects affected / exposed	0 / 64 (0.00%)	0 / 60 (0.00%)	1 / 54 (1.85%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	1 / 1
Complex regional pain syndrome
subjects affected / exposed	0 / 64 (0.00%)	1 / 60 (1.67%)	0 / 54 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Dizziness
subjects affected / exposed	1 / 64 (1.56%)	0 / 60 (0.00%)	0 / 54 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Epilepsy
subjects affected / exposed	1 / 64 (1.56%)	0 / 60 (0.00%)	0 / 54 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Headache
subjects affected / exposed	1 / 64 (1.56%)	0 / 60 (0.00%)	0 / 54 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Hypoxic-ischaemic encephalopathy
subjects affected / exposed	0 / 64 (0.00%)	0 / 60 (0.00%)	1 / 54 (1.85%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Ischaemic stroke
subjects affected / exposed	0 / 64 (0.00%)	1 / 60 (1.67%)	0 / 54 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Somnolence
subjects affected / exposed	1 / 64 (1.56%)	0 / 60 (0.00%)	0 / 54 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Syncope
subjects affected / exposed	2 / 64 (3.13%)	0 / 60 (0.00%)	1 / 54 (1.85%)
occurrences causally related to treatment / all	0 / 3	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	0 / 64 (0.00%)	1 / 60 (1.67%)	2 / 54 (3.70%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Lymphadenopathy
subjects affected / exposed	1 / 64 (1.56%)	0 / 60 (0.00%)	0 / 54 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Ear and labyrinth disorders
Tympanic membrane perforation
subjects affected / exposed	0 / 64 (0.00%)	0 / 60 (0.00%)	1 / 54 (1.85%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Eye disorders
Cataract
subjects affected / exposed	0 / 64 (0.00%)	0 / 60 (0.00%)	1 / 54 (1.85%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Abdominal pain
subjects affected / exposed	0 / 64 (0.00%)	1 / 60 (1.67%)	0 / 54 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Chronic gastritis
subjects affected / exposed	2 / 64 (3.13%)	0 / 60 (0.00%)	0 / 54 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Diarrhoea
subjects affected / exposed	0 / 64 (0.00%)	2 / 60 (3.33%)	0 / 54 (0.00%)
occurrences causally related to treatment / all	0 / 0	2 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Gastric polyps
subjects affected / exposed	1 / 64 (1.56%)	0 / 60 (0.00%)	0 / 54 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Gastritis
subjects affected / exposed	2 / 64 (3.13%)	0 / 60 (0.00%)	0 / 54 (0.00%)
occurrences causally related to treatment / all	1 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Inguinal hernia
subjects affected / exposed	0 / 64 (0.00%)	1 / 60 (1.67%)	0 / 54 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Intestinal dilatation
subjects affected / exposed	0 / 64 (0.00%)	1 / 60 (1.67%)	0 / 54 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Small intestinal obstruction
subjects affected / exposed	0 / 64 (0.00%)	1 / 60 (1.67%)	0 / 54 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Swollen tongue
subjects affected / exposed	1 / 64 (1.56%)	0 / 60 (0.00%)	0 / 54 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Umbilical hernia
subjects affected / exposed	0 / 64 (0.00%)	1 / 60 (1.67%)	0 / 54 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Vomiting
subjects affected / exposed	0 / 64 (0.00%)	0 / 60 (0.00%)	1 / 54 (1.85%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Hepatobiliary disorders
Cholelithiasis
subjects affected / exposed	0 / 64 (0.00%)	1 / 60 (1.67%)	0 / 54 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Skin and subcutaneous tissue disorders
Diabetic foot
subjects affected / exposed	0 / 64 (0.00%)	0 / 60 (0.00%)	1 / 54 (1.85%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Skin ulcer
subjects affected / exposed	0 / 64 (0.00%)	0 / 60 (0.00%)	1 / 54 (1.85%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Night sweats
subjects affected / exposed	1 / 64 (1.56%)	0 / 60 (0.00%)	0 / 54 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Renal and urinary disorders
Acute kidney injury
subjects affected / exposed	1 / 64 (1.56%)	0 / 60 (0.00%)	0 / 54 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0
Glomerulonephritis membranous
subjects affected / exposed	0 / 64 (0.00%)	1 / 60 (1.67%)	0 / 54 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Haematuria
subjects affected / exposed	1 / 64 (1.56%)	0 / 60 (0.00%)	1 / 54 (1.85%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Hydronephrosis
subjects affected / exposed	0 / 64 (0.00%)	1 / 60 (1.67%)	0 / 54 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Nephrotic syndrome
subjects affected / exposed	1 / 64 (1.56%)	0 / 60 (0.00%)	0 / 54 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Renal injury
subjects affected / exposed	1 / 64 (1.56%)	0 / 60 (0.00%)	0 / 54 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Renal mass
subjects affected / exposed	0 / 64 (0.00%)	0 / 60 (0.00%)	1 / 54 (1.85%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Endocrine disorders
Hyperparathyrodism
subjects affected / exposed	0 / 64 (0.00%)	1 / 60 (1.67%)	0 / 54 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Hyperparathyroidism tertiary
subjects affected / exposed	0 / 64 (0.00%)	1 / 60 (1.67%)	0 / 54 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Back pain
subjects affected / exposed	1 / 64 (1.56%)	0 / 60 (0.00%)	0 / 54 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Flank pain
subjects affected / exposed	0 / 64 (0.00%)	0 / 60 (0.00%)	1 / 54 (1.85%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Myalgia
subjects affected / exposed	0 / 64 (0.00%)	1 / 60 (1.67%)	0 / 54 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Osteonecrosis
subjects affected / exposed	1 / 64 (1.56%)	0 / 60 (0.00%)	0 / 54 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Rotator cuff syndrome
subjects affected / exposed	0 / 64 (0.00%)	1 / 60 (1.67%)	0 / 54 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Infections and infestations
Abscess
subjects affected / exposed	0 / 64 (0.00%)	2 / 60 (3.33%)	0 / 54 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Arthritis bacterial
subjects affected / exposed	1 / 64 (1.56%)	0 / 60 (0.00%)	0 / 54 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Aspergilloma
subjects affected / exposed	0 / 64 (0.00%)	0 / 60 (0.00%)	1 / 54 (1.85%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Atypical pneumonia
subjects affected / exposed	1 / 64 (1.56%)	0 / 60 (0.00%)	0 / 54 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Bacteraemia
subjects affected / exposed	1 / 64 (1.56%)	0 / 60 (0.00%)	0 / 54 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Cellulitis
subjects affected / exposed	2 / 64 (3.13%)	2 / 60 (3.33%)	0 / 54 (0.00%)
occurrences causally related to treatment / all	3 / 4	3 / 4	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Cellulitis staphylococcal
subjects affected / exposed	0 / 64 (0.00%)	0 / 60 (0.00%)	1 / 54 (1.85%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Cytomegalovirus chorioretinitis
subjects affected / exposed	0 / 64 (0.00%)	0 / 60 (0.00%)	1 / 54 (1.85%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Cytomegalovirus infection
subjects affected / exposed	0 / 64 (0.00%)	0 / 60 (0.00%)	1 / 54 (1.85%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Diabetic foot infection
subjects affected / exposed	0 / 64 (0.00%)	0 / 60 (0.00%)	1 / 54 (1.85%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Diarrhoea infectious
subjects affected / exposed	0 / 64 (0.00%)	1 / 60 (1.67%)	0 / 54 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Diverticulitis
subjects affected / exposed	0 / 64 (0.00%)	0 / 60 (0.00%)	1 / 54 (1.85%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Ear infection
subjects affected / exposed	0 / 64 (0.00%)	1 / 60 (1.67%)	0 / 54 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Endophthalmitis
subjects affected / exposed	0 / 64 (0.00%)	0 / 60 (0.00%)	1 / 54 (1.85%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Gas gangrene
subjects affected / exposed	0 / 64 (0.00%)	0 / 60 (0.00%)	1 / 54 (1.85%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Gastroenteritis
subjects affected / exposed	1 / 64 (1.56%)	0 / 60 (0.00%)	0 / 54 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Gastroenteritis norovirus
subjects affected / exposed	0 / 64 (0.00%)	2 / 60 (3.33%)	0 / 54 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
H1N1 influenza
subjects affected / exposed	2 / 64 (3.13%)	0 / 60 (0.00%)	0 / 54 (0.00%)
occurrences causally related to treatment / all	1 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Herpes simplex
subjects affected / exposed	0 / 64 (0.00%)	1 / 60 (1.67%)	0 / 54 (0.00%)
occurrences causally related to treatment / all	0 / 0	2 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Herpes zoster
subjects affected / exposed	2 / 64 (3.13%)	2 / 60 (3.33%)	1 / 54 (1.85%)
occurrences causally related to treatment / all	2 / 2	2 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Influenza
subjects affected / exposed	0 / 64 (0.00%)	2 / 60 (3.33%)	0 / 54 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Localised infection
subjects affected / exposed	0 / 64 (0.00%)	0 / 60 (0.00%)	2 / 54 (3.70%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Mycobacterium chelonae infection
subjects affected / exposed	0 / 64 (0.00%)	1 / 60 (1.67%)	0 / 54 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Orchitis
subjects affected / exposed	1 / 64 (1.56%)	0 / 60 (0.00%)	1 / 54 (1.85%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Osteomyelitis
subjects affected / exposed	1 / 64 (1.56%)	0 / 60 (0.00%)	1 / 54 (1.85%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Otitis media acute
subjects affected / exposed	0 / 64 (0.00%)	0 / 60 (0.00%)	1 / 54 (1.85%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Paronychia
subjects affected / exposed	1 / 64 (1.56%)	0 / 60 (0.00%)	0 / 54 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pneumonia
subjects affected / exposed	4 / 64 (6.25%)	3 / 60 (5.00%)	2 / 54 (3.70%)
occurrences causally related to treatment / all	3 / 4	3 / 3	0 / 2
deaths causally related to treatment / all	1 / 1	0 / 0	0 / 0
Pneumonia bacterial
subjects affected / exposed	1 / 64 (1.56%)	0 / 60 (0.00%)	0 / 54 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pneumonia staphylococcal
subjects affected / exposed	0 / 64 (0.00%)	1 / 60 (1.67%)	0 / 54 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Polyomavirus-associated nephropathy
subjects affected / exposed	0 / 64 (0.00%)	3 / 60 (5.00%)	0 / 54 (0.00%)
occurrences causally related to treatment / all	0 / 0	3 / 3	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Postoperative wound infection
subjects affected / exposed	1 / 64 (1.56%)	0 / 60 (0.00%)	0 / 54 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pseudomonal sepsis
subjects affected / exposed	1 / 64 (1.56%)	1 / 60 (1.67%)	0 / 54 (0.00%)
occurrences causally related to treatment / all	1 / 1	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pyelonephritis
subjects affected / exposed	1 / 64 (1.56%)	0 / 60 (0.00%)	1 / 54 (1.85%)
occurrences causally related to treatment / all	1 / 1	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pyelonephritis acute
subjects affected / exposed	0 / 64 (0.00%)	0 / 60 (0.00%)	1 / 54 (1.85%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Respiratory tract infection
subjects affected / exposed	0 / 64 (0.00%)	1 / 60 (1.67%)	0 / 54 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Rhinovirus infection
subjects affected / exposed	0 / 64 (0.00%)	1 / 60 (1.67%)	0 / 54 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Sepsis
subjects affected / exposed	2 / 64 (3.13%)	0 / 60 (0.00%)	3 / 54 (5.56%)
occurrences causally related to treatment / all	2 / 2	0 / 0	1 / 3
deaths causally related to treatment / all	1 / 1	0 / 0	0 / 1
Sinusitis
subjects affected / exposed	2 / 64 (3.13%)	0 / 60 (0.00%)	0 / 54 (0.00%)
occurrences causally related to treatment / all	1 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Staphylococcal bacteraemia
subjects affected / exposed	1 / 64 (1.56%)	0 / 60 (0.00%)	0 / 54 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Staphylococcal sepsis
subjects affected / exposed	0 / 64 (0.00%)	0 / 60 (0.00%)	1 / 54 (1.85%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Tooth abscess
subjects affected / exposed	0 / 64 (0.00%)	1 / 60 (1.67%)	0 / 54 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Upper respiratory tract infection
subjects affected / exposed	0 / 64 (0.00%)	1 / 60 (1.67%)	0 / 54 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Urinary tract infection
subjects affected / exposed	0 / 64 (0.00%)	3 / 60 (5.00%)	0 / 54 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 3	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Urosepsis
subjects affected / exposed	0 / 64 (0.00%)	1 / 60 (1.67%)	0 / 54 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 3	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Wound infection
subjects affected / exposed	0 / 64 (0.00%)	1 / 60 (1.67%)	0 / 54 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Metabolism and nutrition disorders
Diabetes mellitus
subjects affected / exposed	0 / 64 (0.00%)	1 / 60 (1.67%)	0 / 54 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Diabetic ketoacidosis
subjects affected / exposed	1 / 64 (1.56%)	0 / 60 (0.00%)	1 / 54 (1.85%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Fluid retention
subjects affected / exposed	1 / 64 (1.56%)	0 / 60 (0.00%)	0 / 54 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Hypoglycaemia
subjects affected / exposed	0 / 64 (0.00%)	0 / 60 (0.00%)	1 / 54 (1.85%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Hypokalaemia
subjects affected / exposed	0 / 64 (0.00%)	1 / 60 (1.67%)	2 / 54 (3.70%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Hypomagnesaemia
subjects affected / exposed	0 / 64 (0.00%)	0 / 60 (0.00%)	1 / 54 (1.85%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Type 2 diabetes mellitus
subjects affected / exposed	0 / 64 (0.00%)	0 / 60 (0.00%)	1 / 54 (1.85%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	Cyclosporine	Tofacitinib Less Intensive (LI)	Tofacitinib More Intensive (MI)
Total subjects affected by non serious adverse events
subjects affected / exposed	49 / 64 (76.56%)	55 / 60 (91.67%)	45 / 54 (83.33%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Skin papilloma
subjects affected / exposed	4 / 64 (6.25%)	7 / 60 (11.67%)	1 / 54 (1.85%)
occurrences all number	5	9	1
Vascular disorders
Hypertension
subjects affected / exposed	6 / 64 (9.38%)	4 / 60 (6.67%)	4 / 54 (7.41%)
occurrences all number	6	4	4
Haematoma
subjects affected / exposed	4 / 64 (6.25%)	1 / 60 (1.67%)	1 / 54 (1.85%)
occurrences all number	4	1	1
General disorders and administration site conditions
Chest pain
subjects affected / exposed	7 / 64 (10.94%)	2 / 60 (3.33%)	1 / 54 (1.85%)
occurrences all number	8	3	1
Fatigue
subjects affected / exposed	3 / 64 (4.69%)	5 / 60 (8.33%)	5 / 54 (9.26%)
occurrences all number	3	5	5
Peripheral swelling
subjects affected / exposed	3 / 64 (4.69%)	6 / 60 (10.00%)	0 / 54 (0.00%)
occurrences all number	4	6	0
Oedema peripheral
subjects affected / exposed	4 / 64 (6.25%)	10 / 60 (16.67%)	4 / 54 (7.41%)
occurrences all number	8	10	4
Pyrexia
subjects affected / exposed	3 / 64 (4.69%)	7 / 60 (11.67%)	3 / 54 (5.56%)
occurrences all number	4	8	3
Immune system disorders
Transplant rejection
subjects affected / exposed	5 / 64 (7.81%)	1 / 60 (1.67%)	0 / 54 (0.00%)
occurrences all number	7	1	0
Social circumstances
Postmenopause
subjects affected / exposed ^[1]	0 / 20 (0.00%)	0 / 19 (0.00%)	1 / 14 (7.14%)
occurrences all number	0	0	1
Reproductive system and breast disorders
Menorrhagia
subjects affected / exposed ^[2]	0 / 20 (0.00%)	1 / 19 (5.26%)	1 / 14 (7.14%)
occurrences all number	0	1	1
Vulval disorder
subjects affected / exposed ^[3]	0 / 20 (0.00%)	1 / 19 (5.26%)	0 / 14 (0.00%)
occurrences all number	0	1	0
Respiratory, thoracic and mediastinal disorders
Cough
subjects affected / exposed	3 / 64 (4.69%)	4 / 60 (6.67%)	6 / 54 (11.11%)
occurrences all number	3	4	8
Dyspnoea
subjects affected / exposed	3 / 64 (4.69%)	2 / 60 (3.33%)	3 / 54 (5.56%)
occurrences all number	4	2	3
Psychiatric disorders
Anxiety
subjects affected / exposed	1 / 64 (1.56%)	5 / 60 (8.33%)	4 / 54 (7.41%)
occurrences all number	2	7	4
Depression
subjects affected / exposed	2 / 64 (3.13%)	4 / 60 (6.67%)	0 / 54 (0.00%)
occurrences all number	2	4	0
Insomnia
subjects affected / exposed	6 / 64 (9.38%)	3 / 60 (5.00%)	0 / 54 (0.00%)
occurrences all number	6	3	0
Investigations
Blood creatine phosphokinase increased
subjects affected / exposed	3 / 64 (4.69%)	4 / 60 (6.67%)	5 / 54 (9.26%)
occurrences all number	4	4	5
Cardiac murmur
subjects affected / exposed	2 / 64 (3.13%)	4 / 60 (6.67%)	4 / 54 (7.41%)
occurrences all number	2	4	4
Blood creatinine increased
subjects affected / exposed	7 / 64 (10.94%)	1 / 60 (1.67%)	2 / 54 (3.70%)
occurrences all number	8	2	2
Weight decreased
subjects affected / exposed	2 / 64 (3.13%)	5 / 60 (8.33%)	0 / 54 (0.00%)
occurrences all number	2	5	0
Weight increased
subjects affected / exposed	4 / 64 (6.25%)	5 / 60 (8.33%)	3 / 54 (5.56%)
occurrences all number	4	5	3
Injury, poisoning and procedural complications
Fall
subjects affected / exposed	4 / 64 (6.25%)	4 / 60 (6.67%)	6 / 54 (11.11%)
occurrences all number	4	6	6
Nervous system disorders
Dizziness
subjects affected / exposed	4 / 64 (6.25%)	2 / 60 (3.33%)	2 / 54 (3.70%)
occurrences all number	5	2	2
Headache
subjects affected / exposed	8 / 64 (12.50%)	7 / 60 (11.67%)	3 / 54 (5.56%)
occurrences all number	9	9	4
Tremor
subjects affected / exposed	1 / 64 (1.56%)	1 / 60 (1.67%)	3 / 54 (5.56%)
occurrences all number	1	1	3
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	8 / 64 (12.50%)	1 / 60 (1.67%)	3 / 54 (5.56%)
occurrences all number	9	2	6
Gastrointestinal disorders
Abdominal pain upper
subjects affected / exposed	4 / 64 (6.25%)	4 / 60 (6.67%)	1 / 54 (1.85%)
occurrences all number	4	5	1
Abdominal Pain
subjects affected / exposed	4 / 64 (6.25%)	7 / 60 (11.67%)	1 / 54 (1.85%)
occurrences all number	4	8	1
Constipation
subjects affected / exposed	4 / 64 (6.25%)	4 / 60 (6.67%)	2 / 54 (3.70%)
occurrences all number	7	4	2
Diarrhoea
subjects affected / exposed	10 / 64 (15.63%)	9 / 60 (15.00%)	4 / 54 (7.41%)
occurrences all number	12	9	5
Nausea
subjects affected / exposed	6 / 64 (9.38%)	7 / 60 (11.67%)	2 / 54 (3.70%)
occurrences all number	12	7	2
Vomiting
subjects affected / exposed	9 / 64 (14.06%)	8 / 60 (13.33%)	2 / 54 (3.70%)
occurrences all number	12	8	2
Skin and subcutaneous tissue disorders
Acne
subjects affected / exposed	0 / 64 (0.00%)	2 / 60 (3.33%)	3 / 54 (5.56%)
occurrences all number	0	2	3
Actinic keratosis
subjects affected / exposed	2 / 64 (3.13%)	4 / 60 (6.67%)	2 / 54 (3.70%)
occurrences all number	2	4	2
Alopecia
subjects affected / exposed	1 / 64 (1.56%)	6 / 60 (10.00%)	2 / 54 (3.70%)
occurrences all number	1	7	2
Hirsutism
subjects affected / exposed ^[4]	2 / 20 (10.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)
occurrences all number	2	0	0
Pruritus
subjects affected / exposed	0 / 64 (0.00%)	5 / 60 (8.33%)	1 / 54 (1.85%)
occurrences all number	0	5	1
Rash
subjects affected / exposed	0 / 64 (0.00%)	3 / 60 (5.00%)	4 / 54 (7.41%)
occurrences all number	0	3	4
Renal and urinary disorders
Haematuria
subjects affected / exposed	1 / 64 (1.56%)	5 / 60 (8.33%)	1 / 54 (1.85%)
occurrences all number	1	5	1
Proteinuria
subjects affected / exposed	4 / 64 (6.25%)	4 / 60 (6.67%)	3 / 54 (5.56%)
occurrences all number	4	4	3
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	10 / 64 (15.63%)	8 / 60 (13.33%)	7 / 54 (12.96%)
occurrences all number	12	9	7
Back pain
subjects affected / exposed	8 / 64 (12.50%)	4 / 60 (6.67%)	2 / 54 (3.70%)
occurrences all number	11	4	2
Musculoskeletal pain
subjects affected / exposed	3 / 64 (4.69%)	2 / 60 (3.33%)	3 / 54 (5.56%)
occurrences all number	3	2	3
Pain in extremity
subjects affected / exposed	4 / 64 (6.25%)	8 / 60 (13.33%)	2 / 54 (3.70%)
occurrences all number	4	14	3
Infections and infestations
BK virus infection
subjects affected / exposed	0 / 64 (0.00%)	6 / 60 (10.00%)	1 / 54 (1.85%)
occurrences all number	0	8	1
Bronchitis
subjects affected / exposed	4 / 64 (6.25%)	4 / 60 (6.67%)	1 / 54 (1.85%)
occurrences all number	6	4	1
Epstein-Barr viraemia
subjects affected / exposed	1 / 64 (1.56%)	1 / 60 (1.67%)	3 / 54 (5.56%)
occurrences all number	1	1	3
Fungal skin infection
subjects affected / exposed	0 / 64 (0.00%)	1 / 60 (1.67%)	3 / 54 (5.56%)
occurrences all number	0	1	3
Gastroenteritis
subjects affected / exposed	2 / 64 (3.13%)	6 / 60 (10.00%)	2 / 54 (3.70%)
occurrences all number	2	6	2
Herpes zoster
subjects affected / exposed	3 / 64 (4.69%)	11 / 60 (18.33%)	5 / 54 (9.26%)
occurrences all number	3	12	6
Nasopharyngitis
subjects affected / exposed	5 / 64 (7.81%)	4 / 60 (6.67%)	3 / 54 (5.56%)
occurrences all number	8	5	4
Onychomycosis
subjects affected / exposed	2 / 64 (3.13%)	7 / 60 (11.67%)	2 / 54 (3.70%)
occurrences all number	2	7	2
Urinary tract infection
subjects affected / exposed	4 / 64 (6.25%)	4 / 60 (6.67%)	5 / 54 (9.26%)
occurrences all number	5	5	5
Upper respiratory tract infection
subjects affected / exposed	7 / 64 (10.94%)	10 / 60 (16.67%)	13 / 54 (24.07%)
occurrences all number	9	18	15
Metabolism and nutrition disorders
Hyperlipidaemia
subjects affected / exposed	2 / 64 (3.13%)	1 / 60 (1.67%)	5 / 54 (9.26%)
occurrences all number	2	1	5
Hypercholesterolaemia
subjects affected / exposed	1 / 64 (1.56%)	4 / 60 (6.67%)	1 / 54 (1.85%)
occurrences all number	1	5	1
Hypertriglyceridaemia
subjects affected / exposed	0 / 64 (0.00%)	2 / 60 (3.33%)	3 / 54 (5.56%)
occurrences all number	0	2	3
Hypokalaemia
subjects affected / exposed	4 / 64 (6.25%)	1 / 60 (1.67%)	2 / 54 (3.70%)
occurrences all number	4	1	6
Impaired fasting glucose
subjects affected / exposed	0 / 64 (0.00%)	0 / 60 (0.00%)	3 / 54 (5.56%)
occurrences all number	0	0	3
Vitamin D deficiency
subjects affected / exposed	1 / 64 (1.56%)	0 / 60 (0.00%)	3 / 54 (5.56%)
occurrences all number	1	0	3

Notes
[1] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: The adverse event is gender-specific. The total numbers of subjects exposed refers to female subjects only and hence is less than the total number of subjects exposed for the reporting group
[2] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: The adverse event is gender-specific. The total numbers of subjects exposed refers to female subjects only and hence is less than the total number of subjects exposed for the reporting group
[3] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: The adverse event is gender-specific. The total numbers of subjects exposed refers to female subjects only and hence is less than the total number of subjects exposed for the reporting group
[4] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: The adverse event is gender-specific. The total numbers of subjects exposed refers to female subjects only and hence is less than the total number of subjects exposed for the reporting group

More information

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Were there any global substantial amendments to the protocol? Yes

01 May 2009

Required subjects to decrease their tofacitinib dose to 5mg BID by Month 18 posttransplant

26 Mar 2010

Extension of the duration of the A3921050 trial by an additional 3 years through 6 years posttransplant

04 Nov 2010

Discontinuation of subjects with tofacitinib exposure (measured by TWC2 above median) at 6 months posttransplant

28 Feb 2011

Discontinuation of CP-690,550 treated subjects whose EBV serostatus at the time of transplantation was either negative or unknown, have developed CMV disease or have received lymphocyte depleting agents posttransplant

17 Dec 2012

Updated the compound identifiers and template language to comply with the Food and Drug Administration (FDA) Final Rule and/or the European Union ‘CT-3’ guidance

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

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Clinical trials

Clinical Trial Results: A Phase 2, Multicenter, Open-Label, Active Comparator-Controlled, Extension Trial to Evaluate the Long-Term Safety and Efficacy of CP-690,550 in Renal Allograft Recipients

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Kaplan-Meier Analysis of Percentage of Participants with Clinically Significant Infection (CSI) by Visit

Primary: Kaplan-Meier Analysis of Percentage of Participants with Clinically Significant Infection (CSI) by Visit

Primary: Percentage of Participants with Malignancies

Primary: Percentage of Participants with Malignancies

Primary: Least Squares Means of Measured Glomerular Filtration Rate (GFR) (Iohexol Serum Clearance in Milliliters per Minute [mL/min])

Primary: Least Squares Means of Measured Glomerular Filtration Rate (GFR) (Iohexol Serum Clearance in Milliliters per Minute [mL/min])

Primary: Percentage of Participants with Progression of Chronic Allograft Lesions (CAL) at Month 36

Primary: Percentage of Participants with Progression of Chronic Allograft Lesions (CAL) at Month 36

Primary: Kaplan-Meier Analysis of Percentage of Participants with first Biopsy Proven Acute Rejection (BPAR) by Visit

Primary: Kaplan-Meier Analysis of Percentage of Participants with first Biopsy Proven Acute Rejection (BPAR) by Visit

Primary: Kaplan-Meier Analysis of Percentage of Participants with Treated Clinical Acute Rejection (TCAR) by Visit

Primary: Kaplan-Meier Analysis of Percentage of Participants with Treated Clinical Acute Rejection (TCAR) by Visit

Secondary: Kaplan-Meier Analysis of Percentage of Participants with Efficacy Failure by Visit

Secondary: Kaplan-Meier Analysis of Percentage of Participants with Efficacy Failure by Visit

Secondary: Kaplan-Meier Analysis of Percentage of Participants with Combined Banff Rejection (BR) by Visit

Secondary: Kaplan-Meier Analysis of Percentage of Participants with Combined Banff Rejection (BR) by Visit

Secondary: Kaplan-Meier Analysis of Percent of Participants with Graft Survival with Death Censored by Visit

Secondary: Kaplan-Meier Analysis of Percent of Participants with Graft Survival with Death Censored by Visit

Secondary: Kaplan-Meier Analysis of Percentage of Participants Surviving by Visit

Secondary: Kaplan-Meier Analysis of Percentage of Participants Surviving by Visit

Secondary: Percentage of Participants Discontinuing from the Study

Secondary: Percentage of Participants Discontinuing from the Study

Secondary: Least Squares (LS) Means of Total Serum Cholesterol Levels (milligrams per deciliter [mg/dL]) by Visit

Secondary: Least Squares (LS) Means of Total Serum Cholesterol Levels (milligrams per deciliter [mg/dL]) by Visit

Secondary: LS Means of Total Serum Low Density Lipoprotein (LDL) Cholesterol Levels (mg/dL) by Visit

Secondary: LS Means of Total Serum Low Density Lipoprotein (LDL) Cholesterol Levels (mg/dL) by Visit

Secondary: LS Means of Total Serum High Density Lipoprotein (HDL) Cholesterol Levels (mg/dL) by Visit

Secondary: LS Means of Total Serum High Density Lipoprotein (HDL) Cholesterol Levels (mg/dL) by Visit

Secondary: LS Means of Total Serum Triglycerides (mg/dL) by Visit

Secondary: LS Means of Total Serum Triglycerides (mg/dL) by Visit

Secondary: Mean Absolute Neutrophil Counts (ANC) (kelvin per millimeter cubed [K/mm^3]) by Visit

Secondary: Mean Absolute Neutrophil Counts (ANC) (kelvin per millimeter cubed [K/mm^3]) by Visit

Secondary: Mean Hemoglobin (Hgb) (grams per deciliter [g/dL]) by Visit

Secondary: Mean Hemoglobin (Hgb) (grams per deciliter [g/dL]) by Visit

Secondary: Mean Glycosylated Hemoglobin (HBA1c) (%) by Visit

Secondary: Mean Glycosylated Hemoglobin (HBA1c) (%) by Visit

Secondary: LS Means of Fasting Serum Glucose Levels (mg/dL) by Visit

Secondary: LS Means of Fasting Serum Glucose Levels (mg/dL) by Visit

Secondary: Percentage of Participants by Proteinuria Category by Visit

Secondary: Percentage of Participants by Proteinuria Category by Visit

Secondary: LS Means of Estimated GFR Calculated Using the Nankivell Equation by Visit

Secondary: LS Means of Estimated GFR Calculated Using the Nankivell Equation by Visit

Secondary: LS Means of Estimated GFR Calculated Using the Cockcroft-Gault Equation by Visit

Secondary: LS Means of Estimated GFR Calculated Using the Cockcroft-Gault Equation by Visit

Secondary: LS Means of estimated GFR (eGFR) (mL/min/1.73m^2) Calculated by the Modification of Diet in Renal Disease (MDRD) Equation With Last Observation Carried Forward (LOCF) plus Imputation (eGFR=0 for graft loss/death) by Visit

Secondary: LS Means of estimated GFR (eGFR) (mL/min/1.73m^2) Calculated by the Modification of Diet in Renal Disease (MDRD) Equation With Last Observation Carried Forward (LOCF) plus Imputation (eGFR=0 for graft loss/death) by Visit

Secondary: LS Means of Short Form 36 Version 2 (SF-36 V2) Component and Domain Scores at Months 24 and 36

Secondary: LS Means of Short Form 36 Version 2 (SF-36 V2) Component and Domain Scores at Months 24 and 36

Secondary: LS Means of End-Stage Renal Disease (ESRD) Symptom Checklist (SCL) -Transplantation Modules at Months 24 and 36

Secondary: LS Means of End-Stage Renal Disease (ESRD) Symptom Checklist (SCL) -Transplantation Modules at Months 24 and 36

Secondary: LSMeans of Severity of Dyspepsia Assessment (SODA) Subscales at Months 24 & 36

Secondary: LSMeans of Severity of Dyspepsia Assessment (SODA) Subscales at Months 24 & 36

Secondary: Mean Trough Levels of Tofacitinib by Visit

Secondary: Mean Trough Levels of Tofacitinib by Visit

Secondary: Mean Trough Levels of Cyclosporine by Visit

Secondary: Mean Trough Levels of Cyclosporine by Visit

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
A Phase 2, Multicenter, Open-Label, Active Comparator-Controlled, Extension Trial to Evaluate the Long-Term Safety and Efficacy of CP-690,550 in Renal Allograft Recipients