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Clinical Trial Results:
A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Dose-Ranging Study of the Efficacy and Safety of Tofacitinib in Subjects with Active Ankylosing Spondylitis (AS)

Summary
EudraCT number	2011-005689-39
Trial protocol	HU CZ ES NL SK
Global end of trial date	18 Mar 2015

Results information
Results version number	v1(current)
This version publication date	03 Apr 2016
First version publication date	03 Apr 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

A3921119

ISRCTN number

US NCT number

NCT01786668

WHO universal trial number (UTN)

Sponsor organisation name

Pfizer Inc.

Sponsor organisation address

235 E 42nd Street, New York, United States, NY 10017

Public contact

Pfizer ClinicalTrials.gov Call Center, Pfizer Inc., 001 800-718-1021, ClinicalTrials.gov_Inquiries@pfizer.com

Scientific contact

Pfizer ClinicalTrials.gov Call Center, Pfizer Inc., 001 800-718-1021, 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

18 Mar 2015

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

18 Mar 2015

Was the trial ended prematurely?

Main objective of the trial

This was a Phase 2, multicentre, randomised, double-blind, placebo-controlled dose ranging, parallel group efficacy and safety study designed to characterise the dose response of tofacitinib in participants with active AS.

Protection of trial subjects

This study was conducted in compliance with the ethical principles originating in or derived from the Declaration of Helsinki (World Medical Association 1996 and 2008) and in compliance with all International Conference on Harmonization Good Clinical Practice Guidelines, as well as the general principles set forth in the International Ethical Guidelines for Biomedical Research Involving Human Subjects (Council for International Organizations of Medical Sciences 2002). In addition, all local regulatory requirements were followed, in particular, those affording greater protection to the safety of trial participants. The final protocol and amendments were reviewed and approved by the Institutional Review Board(s) and/or Independent Ethics Committee(s) at each of the investigational centres participating in the study.

Background therapy

Evidence for comparator

Actual start date of recruitment

17 Apr 2013

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

Canada: 5

Country: Number of subjects enrolled

Czech Republic: 19

Country: Number of subjects enrolled

Hungary: 33

Country: Number of subjects enrolled

Korea, Republic of: 8

Country: Number of subjects enrolled

Poland: 67

Country: Number of subjects enrolled

Russian Federation: 12

Country: Number of subjects enrolled

Spain: 9

Country: Number of subjects enrolled

Taiwan: 31

Country: Number of subjects enrolled

United States: 23

Worldwide total number of subjects

207

EEA total number of subjects

128

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)

196

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

Screening details

A diagnosis of AS based on the Modified New York Criteria for AS (1984) with active disease defined as a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score of greater than or equal to (≥) 4 and back pain score (BASDAI Question 2) of ≥4 despite treatment with nonsteroidal anti-inflammatory drugs (NSAIDs) (or intolerance to NSAIDs).

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Investigator, Subject

Are arms mutually exclusive

Yes

Tofacitinib 2 mg BID

Arm description

Participants were administered 4 tablets (two 1 mg tablets of tofacitinib along with two 5 mg matching placebo tablets) orally BID (in the AM and PM) for a total of 12 weeks.

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

Two 1 mg tablets of tofacitinib along with two 5 mg matching placebo tablets administered orally BID (in the AM and PM) for a total of 12 weeks.

Tofacitinib 5 mg BID

Arm description

Participants were administered 4 tablets (one 5 mg tablet of tofacitinib, one 5 mg and two 1 mg matching placebo tablets) orally BID (in the AM and PM) for a total of 12 weeks.

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

One 5 mg tablets of tofacitinib along with one 5 mg and two 1 mg matching placebo tablets administered orally BID (in the AM and PM) for a total of 12 weeks.

Tofacitinib 10 mg BID

Arm description

Participants were administered 4 tablets (two 5 mg tablets of tofacitinib and two 1 mg matching placebo tablets) orally twice a day (in the AM and PM) for a total of 12 weeks.

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

Two 5 mg tablets of tofacitinib along with two 1 mg matching placebo tablets administered orally BID (in the AM and PM) for a total of 12 weeks.

Placebo BID

Arm description

Participants were administered 4 tablets (two 1 mg placebo tablets and two 5 mg matching placebo tablets) orally twice a day (in the AM and PM) for a total of 12 weeks.

Arm type

Placebo

Investigational medicinal product name

Placebo for tofacitinib

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Two 1 mg matching placebo tablets along with two 5 mg matching placebo tablets administered orally BID (in the AM and PM) for a total of 12 weeks.

Number of subjects in period 1	Tofacitinib 2 mg BID	Tofacitinib 5 mg BID	Tofacitinib 10 mg BID	Placebo BID
Started	52	52	52	51
Completed	51	51	47	47
Not completed	1	1	5	4
Consent withdrawn by subject	-	-	3	1
Adverse event, non-fatal	-	1	1	2
Pregnancy	-	-	-	1
Lost to follow-up	1	-	1	-

Baseline characteristics

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Reporting group title

Tofacitinib 2 mg BID

Reporting group description

Participants were administered 4 tablets (two 1 mg tablets of tofacitinib along with two 5 mg matching placebo tablets) orally BID (in the AM and PM) for a total of 12 weeks.

Reporting group title

Tofacitinib 5 mg BID

Reporting group description

Participants were administered 4 tablets (one 5 mg tablet of tofacitinib, one 5 mg and two 1 mg matching placebo tablets) orally BID (in the AM and PM) for a total of 12 weeks.

Reporting group title

Tofacitinib 10 mg BID

Reporting group description

Participants were administered 4 tablets (two 5 mg tablets of tofacitinib and two 1 mg matching placebo tablets) orally twice a day (in the AM and PM) for a total of 12 weeks.

Reporting group title

Placebo BID

Reporting group description

Participants were administered 4 tablets (two 1 mg placebo tablets and two 5 mg matching placebo tablets) orally twice a day (in the AM and PM) for a total of 12 weeks.

Reporting group values	Tofacitinib 2 mg BID	Tofacitinib 5 mg BID	Tofacitinib 10 mg BID	Placebo BID	Total
Number of subjects	52	52	52	51	207
Age categorical
Units: Subjects
Adults (18-64 years)	49	51	49	47	196
Elderly (from 65-84 years)	3	1	3	4	11
Age Continuous \| Age
Units: Years
arithmetic mean (standard deviation)	41.8 ( 12.3 )	41.2 ( 10.3 )	41.6 ( 12.2 )	41.9 ( 12.9 )	-
Gender, Male/Female
Units: Participants
Female	18	13	14	19	64
Male	34	39	38	32	143

End points

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Reporting group title

Tofacitinib 2 mg BID

Reporting group description

Participants were administered 4 tablets (two 1 mg tablets of tofacitinib along with two 5 mg matching placebo tablets) orally BID (in the AM and PM) for a total of 12 weeks.

Reporting group title

Tofacitinib 5 mg BID

Reporting group description

Participants were administered 4 tablets (one 5 mg tablet of tofacitinib, one 5 mg and two 1 mg matching placebo tablets) orally BID (in the AM and PM) for a total of 12 weeks.

Reporting group title

Tofacitinib 10 mg BID

Reporting group description

Participants were administered 4 tablets (two 5 mg tablets of tofacitinib and two 1 mg matching placebo tablets) orally twice a day (in the AM and PM) for a total of 12 weeks.

Reporting group title

Placebo BID

Reporting group description

Participants were administered 4 tablets (two 1 mg placebo tablets and two 5 mg matching placebo tablets) orally twice a day (in the AM and PM) for a total of 12 weeks.

Primary: Percentage of Participants Achieving 20 Percent (%) Improvement in Assessment of SpondyloArthritis International Society (ASAS) Score (ASAS 20) at Week 12

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End point title

Percentage of Participants Achieving 20 Percent (%) Improvement in Assessment of SpondyloArthritis International Society (ASAS) Score (ASAS 20) at Week 12

End point description

The primary analysis of this outcome measure was performed using the Emax model. Clinical response to treatment was assessed according to ASAS20 criteria. ASAS20 responder had improvement of ≥20% and ≥1 unit in at least 3 domains (on a scale of 0 [least] to 10 [worst]) and no worsening of ≥20% and less than or equal to (≤)1 unit in the remaining domain. The domains are: Patient's Global Assessment of Disease Activity, spinal pain, function and inflammation (from BASDAI). Missing data were handled by nonresponsive (NRI)/ last observation carried forward (LOCF). Missing values due to a participant dropping out from the study were handled by setting the ASAS20 value to NRI. The LOCF approach was applied to missing components, if just some of the components of the ASAS20 were missing. Analysis population is the Full Analysis Set (FAS) which included all participants who were randomized to the study and received at least one dose of the randomized study drug (tofacitinib or placebo).

End point type

Primary

End point timeframe

Week 12

End point values	Tofacitinib 2 mg BID	Tofacitinib 5 mg BID	Tofacitinib 10 mg BID	Placebo BID
Number of subjects analysed	52	52	52	51
Units: Percentage of participants
number (not applicable)	56	63	67.4	40.1

Analysis of ASAS20 at Week 12

Statistical analysis description

Emax model with 95% credible interval computed - 95% confidence interval below represents 95% credible interval.

Comparison groups

Tofacitinib 2 mg BID v Placebo BID

Number of subjects included in analysis

103

Analysis specification

Pre-specified

Analysis type

Method

Emax Model

Parameter type

Risk difference (RD)

Point estimate

15.8

Confidence interval

level

95%

sides

2-sided

lower limit

upper limit

30.3

Analysis of ASAS20 at Week 12

Statistical analysis description

Emax model with 95% credible interval computed - 95% confidence interval below represents 95% credible interval.

Comparison groups

Tofacitinib 5 mg BID v Placebo BID

Number of subjects included in analysis

103

Analysis specification

Pre-specified

Analysis type

Method

Emax Model

Parameter type

Risk difference (RD)

Point estimate

22.9

Confidence interval

level

95%

sides

2-sided

lower limit

8.4

upper limit

37.7

Analysis of ASAS20 at Week 12

Statistical analysis description

Emax model with 95% credible interval computed - 95% confidence interval below represents 95% credible interval.

Comparison groups

Tofacitinib 10 mg BID v Placebo BID

Number of subjects included in analysis

103

Analysis specification

Pre-specified

Analysis type

Method

Emax Model

Parameter type

Risk difference (RD)

Point estimate

27.3

Confidence interval

level

95%

sides

2-sided

lower limit

10.7

upper limit

43.4

Primary: Percentage of Participants Achieving ASAS20 at Week 12

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End point title

Percentage of Participants Achieving ASAS20 at Week 12

End point description

The supportive analysis of this outcome measure was performed using the normal approximation for two proportions. Clinical response to treatment was assessed according to ASAS20 criteria. ASAS20 responder had improvement of ≥ 20% and ≥1 unit in at least 3 domains (on a scale of 0 [least] to 10 [worst]) and no worsening of ≥20% and ≤1 unit in the remaining domain. The domains are: Patient's Global Assessment of Disease Activity, spinal pain, function and inflammation (from BASDAI). Missing data were handled by NRI/LOCF. Missing values due to a participant dropping out from the study were handled by setting the ASAS20 value to NRI. The LOCF approach was applied to missing components, if just some of the components of the ASAS20 were missing. Analysis population is the FAS.

End point type

Primary

End point timeframe

Baseline, Week 12

End point values	Tofacitinib 2 mg BID	Tofacitinib 5 mg BID	Tofacitinib 10 mg BID	Placebo BID
Number of subjects analysed	52	52	52	51
Units: Percentage of participants
number (not applicable)	51.92	80.77	55.77	41.18

Analysis of ASAS20 at Week 12

Comparison groups

Tofacitinib 2 mg BID v Placebo BID

Number of subjects included in analysis

103

Analysis specification

Pre-specified

Analysis type

^[1]

P-value

= 0.271

Method

Normal approximation for two proportions

Parameter type

Risk difference (RD)

Point estimate

10.75

Confidence interval

level

95%

sides

2-sided

lower limit

-8.41

upper limit

29.9

Variability estimate

Standard error of the mean

Dispersion value

9.77

Notes
[1] - The variability estimate standard error of the mean is the standard error of the risk difference.

Analysis of ASAS20 at Week 12

Comparison groups

Tofacitinib 5 mg BID v Placebo BID

Number of subjects included in analysis

103

Analysis specification

Pre-specified

Analysis type

^[2]

P-value

< 0.001

Method

Normal approximation for two proportions

Parameter type

Risk difference (RD)

Point estimate

39.59

Confidence interval

level

95%

sides

2-sided

lower limit

22.35

upper limit

56.83

Variability estimate

Standard error of the mean

Dispersion value

8.8

Notes
[2] - The variability estimate standard error of the mean is the standard error of the risk difference.

Analysis of ASAS20 at Week 12

Comparison groups

Tofacitinib 10 mg BID v Placebo BID

Number of subjects included in analysis

103

Analysis specification

Pre-specified

Analysis type

^[3]

P-value

= 0.134

Method

Normal approximation for two proportions

Parameter type

Risk difference (RD)

Point estimate

14.59

Confidence interval

level

95%

sides

2-sided

lower limit

-4.5

upper limit

33.69

Variability estimate

Standard error of the mean

Dispersion value

9.74

Notes
[3] - The variability estimate standard error of the mean is the standard error of the risk difference.

Secondary: Percentage of Participants Achieving 20% Improvement in ASAS Score at Weeks 2, 4 and 8

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End point title

Percentage of Participants Achieving 20% Improvement in ASAS Score at Weeks 2, 4 and 8

End point description

Clinical response to treatment was assessed according to ASAS20 criteria. ASAS20 responder had improvement of ≥ 20% and ≥1 unit in at least 3 domains (on a scale of 0 [least] to 10 [worst]) and no worsening of ≥20% and ≤1 unit in the remaining domain. The domains are: Patient's Global Assessment of Disease Activity, spinal pain, function and inflammation (from BASDAI). Missing data were handled by NRI/LOCF. Missing values due to a participant dropping out from the study were handled by setting the ASAS20 value to NRI. The LOCF approach was applied to missing components, if just some of the components of the ASAS20 were missing. Analysis population is the FAS, n is the number of responders at each visit.

End point type

Secondary

End point timeframe

Baseline, Week 2, Week 4, Week 8

End point values	Tofacitinib 2 mg BID	Tofacitinib 5 mg BID	Tofacitinib 10 mg BID	Placebo BID
Number of subjects analysed	52	52	52	51
Units: Percentage of participants
number (not applicable)
Week 2 (n=21,17,18,14)	40.38	32.69	34.62	27.45
Week 4 (n=25,29,25,17)	48.08	55.77	48.08	33.33
Week 8 (n=30, 37, 28, 22)	57.69	71.15	53.85	43.14

Analysis of ASAS20 at Week 2

Statistical analysis description

Week 2

Comparison groups

Tofacitinib 2 mg BID v Placebo BID

Number of subjects included in analysis

103

Analysis specification

Pre-specified

Analysis type

^[4]

P-value

= 0.162

Method

Normal approximation for two proportions

Parameter type

Risk difference (RD)

Point estimate

12.93

Confidence interval

level

95%

sides

2-sided

lower limit

-5.17

upper limit

31.04

Variability estimate

Standard error of the mean

Dispersion value

9.24

Notes
[4] - The variability estimate standard error of the mean is the standard error of the risk difference.

Analysis of ASAS20 at Week 2

Statistical analysis description

Week 2

Comparison groups

Tofacitinib 5 mg BID v Placebo BID

Number of subjects included in analysis

103

Analysis specification

Pre-specified

Analysis type

^[5]

P-value

= 0.561

Method

Normal approximation for two proportions

Parameter type

Risk difference (RD)

Point estimate

5.24

Confidence interval

level

95%

sides

2-sided

lower limit

-12.44

upper limit

22.92

Variability estimate

Standard error of the mean

Dispersion value

9.02

Notes
[5] - The variability estimate standard error of the mean is the standard error of the risk difference.

Analysis of ASAS20 at Week 2

Statistical analysis description

Week 2

Comparison groups

Tofacitinib 10 mg BID v Placebo BID

Number of subjects included in analysis

103

Analysis specification

Pre-specified

Analysis type

^[6]

P-value

= 0.43

Method

Normal approximation for two proportions

Parameter type

Risk difference (RD)

Point estimate

7.16

Confidence interval

level

95%

sides

2-sided

lower limit

-10.65

upper limit

24.97

Variability estimate

Standard error of the mean

Dispersion value

9.09

Notes
[6] - The variability estimate standard error of the mean is the standard error of the risk difference.

Analysis of ASAS20 at Week 4

Statistical analysis description

Week 4

Comparison groups

Tofacitinib 2 mg BID v Placebo BID

Number of subjects included in analysis

103

Analysis specification

Pre-specified

Analysis type

^[7]

P-value

= 0.123

Method

Normal approximation for two proportions

Parameter type

Risk difference (RD)

Point estimate

14.74

Confidence interval

level

95%

sides

2-sided

lower limit

-4.01

upper limit

33.5

Variability estimate

Standard error of the mean

Dispersion value

9.57

Notes
[7] - The variability estimate standard error of the mean is the standard error of the risk difference.

Analysis of ASAS20 at Week 4

Statistical analysis description

Week 4

Comparison groups

Tofacitinib 5 mg BID v Placebo BID

Number of subjects included in analysis

103

Analysis specification

Pre-specified

Analysis type

^[8]

P-value

= 0.019

Method

Normal approximation for two proportions

Parameter type

Risk difference (RD)

Point estimate

22.44

Confidence interval

level

95%

sides

2-sided

lower limit

3.74

upper limit

41.13

Variability estimate

Standard error of the mean

Dispersion value

9.54

Notes
[8] - The variability estimate standard error of the mean is the standard error of the risk difference.

Analysis of ASAS20 at Week 4

Statistical analysis description

Week 4

Comparison groups

Tofacitinib 10 mg BID v Placebo BID

Number of subjects included in analysis

103

Analysis specification

Pre-specified

Analysis type

^[9]

P-value

= 0.123

Method

Normal approximation for two proportions

Parameter type

Risk difference (RD)

Point estimate

14.74

Confidence interval

level

95%

sides

2-sided

lower limit

-4.01

upper limit

33.5

Variability estimate

Standard error of the mean

Dispersion value

9.57

Notes
[9] - The variability estimate standard error of the mean is the standard error of the risk difference.

Analysis of ASAS20 at Week 8

Statistical analysis description

Week 8

Comparison groups

Tofacitinib 2 mg BID v Placebo BID

Number of subjects included in analysis

103

Analysis specification

Pre-specified

Analysis type

^[10]

P-value

= 0.135

Method

Normal approximation for two proportions

Parameter type

Risk difference (RD)

Point estimate

14.56

Confidence interval

level

95%

sides

2-sided

lower limit

-4.55

upper limit

33.66

Variability estimate

Standard error of the mean

Dispersion value

9.75

Notes
[10] - The variability estimate standard error of the mean is the standard error of the risk difference.

Analysis of ASAS20 at Week 8

Statistical analysis description

Week 8

Comparison groups

Tofacitinib 5 mg BID v Placebo BID

Number of subjects included in analysis

103

Analysis specification

Pre-specified

Analysis type

^[11]

P-value

= 0.003

Method

Normal approximation for two proportions

Parameter type

Risk difference (RD)

Point estimate

28.02

Confidence interval

level

95%

sides

2-sided

lower limit

9.68

upper limit

46.36

Variability estimate

Standard error of the mean

Dispersion value

9.36

Notes
[11] - The variability estimate standard error of the mean is the standard error of the risk difference.

Analysis of ASAS20 at Week 8

Statistical analysis description

Week 8

Comparison groups

Tofacitinib 10 mg BID v Placebo BID

Number of subjects included in analysis

103

Analysis specification

Pre-specified

Analysis type

^[12]

P-value

= 0.274

Method

Normal approximation for two proportions

Parameter type

Risk difference (RD)

Point estimate

10.71

Confidence interval

level

95%

sides

2-sided

lower limit

-8.48

upper limit

29.9

Variability estimate

Standard error of the mean

Dispersion value

9.79

Notes
[12] - The variability estimate standard error of the mean is the standard error of the risk difference.

Secondary: Change from Baseline in Spondyloarthritis Research Consortium of Canada (SPARCC) Magnetic Resonance Imaging (MRI) Index of Disease Activity Score of the Sacroiliac (SI) Joints at Week 12

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End point title

Change from Baseline in Spondyloarthritis Research Consortium of Canada (SPARCC) Magnetic Resonance Imaging (MRI) Index of Disease Activity Score of the Sacroiliac (SI) Joints at Week 12

End point description

SPARCC scoring consists of assessing six SI joint MRI image coronal slices representing the largest proportion of the synovial compartment of the SI joints for edema. The maximum score per slice was 2 and 12 for all 6 slices. The total maximum score for all SI joints across 6 slices is 72 and higher scores indicate more inflammation. A negative change from baseline indicates improvement. Missing data at Week 12 were imputed by LOCF if data at an early visit (discontinuation visit) were available. Analysis population is the FAS, when change from baseline is analysed FAS requires that participants have a baseline and at least one post-baseline measurement.

End point type

Secondary

End point timeframe

Baseline, Week 12

End point values	Tofacitinib 2 mg BID	Tofacitinib 5 mg BID	Tofacitinib 10 mg BID	Placebo BID
Number of subjects analysed	42	44	44	34
Units: Units on a scale
least squares mean (standard error)	-1.7 ( 0.779 )	-3.15 ( 0.788 )	-3.55 ( 0.795 )	-0.81 ( 0.806 )

Analysis of SPARCC MRI (SI Joints) at Week 12

Comparison groups

Tofacitinib 2 mg BID v Placebo BID

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.427

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-0.89

Confidence interval

level

95%

sides

2-sided

lower limit

-3.11

upper limit

1.32

Variability estimate

Standard error of the mean

Dispersion value

1.123

Analysis of SPARCC MRI (SI Joints) at Week 12

Comparison groups

Tofacitinib 5 mg BID v Placebo BID

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.039

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-2.35

Confidence interval

level

95%

sides

2-sided

lower limit

-4.58

upper limit

-0.12

Variability estimate

Standard error of the mean

Dispersion value

1.13

Analysis of SPARCC MRI (SI Joints) at Week 12

Comparison groups

Tofacitinib 10 mg BID v Placebo BID

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.016

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-2.74

Confidence interval

level

95%

sides

2-sided

lower limit

-4.97

upper limit

-0.51

Variability estimate

Standard error of the mean

Dispersion value

1.131

Secondary: Change from Baseline in SPARCC MRI Index of Disease Activity Score of the Spine at Week 12

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End point title

Change from Baseline in SPARCC MRI Index of Disease Activity Score of the Spine at Week 12

End point description

SPARCC scoring of the MRI of the spine consists of assessing six disco-vertebral units (DVU) with 3 consecutive sagittal slices at each DVU. The maximum SPARCC score for all 6 DVUs is 108, with higher scores indicating more damage. A negative change from baseline indicates improvement. Missing data at Week 12 were imputed by LOCF if data at an early visit (discontinuation visit) were available. Analysis population is the FAS, when change from baseline is analysed FAS requires that participants have a baseline and at least one post-baseline measurement.

End point type

Secondary

End point timeframe

Baseline, Week 12

End point values	Tofacitinib 2 mg BID	Tofacitinib 5 mg BID	Tofacitinib 10 mg BID	Placebo BID
Number of subjects analysed	41	44	44	34
Units: Units on a scale
least squares mean (standard error)	-3.09 ( 1.061 )	-5.51 ( 1.063 )	-6.57 ( 1.073 )	-0.09 ( 1.085 )

Analysis of SPARCC MRI (Spine) at Week 12

Comparison groups

Tofacitinib 2 mg BID v Placebo BID

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.05

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-3

Confidence interval

level

95%

sides

2-sided

lower limit

-5.99

upper limit

Variability estimate

Standard error of the mean

Dispersion value

1.517

Analysis of SPARCC MRI (Spine) at Week 12

Comparison groups

Tofacitinib 5 mg BID v Placebo BID

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

< 0.001

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-5.42

Confidence interval

level

95%

sides

2-sided

lower limit

-8.42

upper limit

-2.42

Variability estimate

Standard error of the mean

Dispersion value

1.52

Analysis of SPARCC MRI (Spine) at Week 12

Comparison groups

Tofacitinib 10 mg BID v Placebo BID

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

< 0.001

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-6.47

Confidence interval

level

95%

sides

2-sided

lower limit

-9.48

upper limit

-3.46

Variability estimate

Standard error of the mean

Dispersion value

1.525

Secondary: Change from Baseline in Modified Berlin Ankylosing Spondylitis Spine Magnetic Resonance Imaging Activity Score (ASspiMRI) of the Spine at Week 12

Top of page

End point title

Change from Baseline in Modified Berlin Ankylosing Spondylitis Spine Magnetic Resonance Imaging Activity Score (ASspiMRI) of the Spine at Week 12

End point description

Berlin modification of the ASspiMRI is a measure of acute lesion as determined by short-tau inversion recovery (STIR) sequences. All 23 DVU of the spine (from C2 to S1), defined as the region between 2 virtual lines through the middle of each vertebra, were scored in a single dimension, which is represented the highest level of inflammation in that particular DVU. Total spine ASspiMRI scores can range from 0-69 with higher scores indicating more disease activity. A negative change from baseline indicates improvement. Missing data at Week 12 were imputed by LOCF if data at an early visit (discontinuation visit) were available. Analysis population is the FAS, when change from baseline is analysed FAS requires that participants have a baseline and at least one post-baseline measurement.

End point type

Secondary

End point timeframe

Baseline, Week 12

End point values	Tofacitinib 2 mg BID	Tofacitinib 5 mg BID	Tofacitinib 10 mg BID	Placebo BID
Number of subjects analysed	41	44	44	34
Units: Units on a scale
least squares mean (standard error)	-1.05 ( 0.364 )	-2.22 ( 0.364 )	-2.13 ( 0.368 )	-0.41 ( 0.372 )

Analysis of ASspiMRI of the Spine at Week 12

Comparison groups

Tofacitinib 2 mg BID v Placebo BID

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.221

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-0.64

Confidence interval

level

95%

sides

2-sided

lower limit

-1.66

upper limit

0.39

Variability estimate

Standard error of the mean

Dispersion value

0.52

Analysis of ASspiMRI of the Spine at Week 12

Comparison groups

Tofacitinib 5 mg BID v Placebo BID

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

< 0.001

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-1.8

Confidence interval

level

95%

sides

2-sided

lower limit

-2.83

upper limit

-0.78

Variability estimate

Standard error of the mean

Dispersion value

0.52

Analysis of ASspiMRI of the Spine at Week 12

Comparison groups

Tofacitinib 10 mg BID v Placebo BID

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.001

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-1.71

Confidence interval

level

95%

sides

2-sided

lower limit

-2.75

upper limit

-0.68

Variability estimate

Standard error of the mean

Dispersion value

0.523

Secondary: Percentage of Participants Achieving 40% Improvement in ASAS score at weeks 2, 4, 8 and 12

Top of page

End point title

Percentage of Participants Achieving 40% Improvement in ASAS score at weeks 2, 4, 8 and 12

End point description

ASAS 40 is defined as ≥40% and absolute change of ≥2 units in at least 3 domains on a 0-10 scale (0=no disease activity, 10=high disease activity), and no worsening in the remaining domain. Missing data were handled by NRI/LOCF. Analysis population is the FAS, n is the number of responders at each visit.

End point type

Secondary

End point timeframe

Baseline, Week 2, Week 4, Week 8, Week 12

End point values	Tofacitinib 2 mg BID	Tofacitinib 5 mg BID	Tofacitinib 10 mg BID	Placebo BID
Number of subjects analysed	52	52	52	51
Units: Percentage of participants
number (not applicable)
Week 2 (n=7, 7, 9, 8)	13.46	13.46	17.31	15.69
Week 4 (n=15, 17, 11, 8)	28.85	32.69	21.15	15.69
Week 8 (n=15, 18, 19, 14)	28.85	34.62	36.54	27.45
Week 12 (n=22, 24, 20, 10)	42.31	46.15	38.46	19.61

Analysis of ASAS 40 at Week 2

Statistical analysis description

Week 2

Comparison groups

Tofacitinib 2 mg BID v Placebo BID

Number of subjects included in analysis

103

Analysis specification

Pre-specified

Analysis type

^[13]

P-value

= 0.749

Method

Normal approximation for two proportions

Parameter type

Risk difference (RD)

Point estimate

-2.22

Confidence interval

level

95%

sides

2-sided

lower limit

-15.85

upper limit

11.4

Variability estimate

Standard error of the mean

Dispersion value

6.95

Notes
[13] - The variability estimate standard error of the mean is the standard error of the risk difference.

Analysis of ASAS 40 at Week 2

Statistical analysis description

Week 2

Comparison groups

Tofacitinib 5 mg BID v Placebo BID

Number of subjects included in analysis

103

Analysis specification

Pre-specified

Analysis type

^[14]

P-value

= 0.749

Method

Normal approximation for two proportions

Parameter type

Risk difference (RD)

Point estimate

-2.22

Confidence interval

level

95%

sides

2-sided

lower limit

-15.85

upper limit

11.4

Variability estimate

Standard error of the mean

Dispersion value

6.95

Notes
[14] - The variability estimate standard error of the mean is the standard error of the risk difference.

Analysis of ASAS 40 at Week 2

Statistical analysis description

Week 2

Comparison groups

Tofacitinib 10 mg BID v Placebo BID

Number of subjects included in analysis

103

Analysis specification

Pre-specified

Analysis type

^[15]

P-value

= 0.824

Method

Normal approximation for two proportions

Parameter type

Risk difference (RD)

Point estimate

1.62

Confidence interval

level

95%

sides

2-sided

lower limit

-12.71

upper limit

15.95

Variability estimate

Standard error of the mean

Dispersion value

7.31

Notes
[15] - The variability estimate standard error of the mean is the standard error of the risk difference.

Analysis of ASAS 40 at Week 4

Statistical analysis description

Week 4

Comparison groups

Tofacitinib 2 mg BID v Placebo BID

Number of subjects included in analysis

103

Analysis specification

Pre-specified

Analysis type

^[16]

P-value

= 0.104

Method

Normal approximation for two proportions

Parameter type

Risk difference (RD)

Point estimate

13.16

Confidence interval

level

95%

sides

2-sided

lower limit

-2.69

upper limit

29.01

Variability estimate

Standard error of the mean

Dispersion value

8.09

Notes
[16] - The variability estimate standard error of the mean is the standard error of the risk difference.

Analysis of ASAS 40 at Week 4

Statistical analysis description

Week 4

Comparison groups

Tofacitinib 5 mg BID v Placebo BID

Number of subjects included in analysis

103

Analysis specification

Pre-specified

Analysis type

^[17]

P-value

= 0.04

Method

Normal approximation for two proportions

Parameter type

Risk difference (RD)

Point estimate

17.01

Confidence interval

level

95%

sides

2-sided

lower limit

0.81

upper limit

33.2

Variability estimate

Standard error of the mean

Dispersion value

8.26

Notes
[17] - The variability estimate standard error of the mean is the standard error of the risk difference.

Analysis of ASAS 40 at Week 4

Statistical analysis description

Week 4

Comparison groups

Tofacitinib 10 mg BID v Placebo BID

Number of subjects included in analysis

103

Analysis specification

Pre-specified

Analysis type

^[18]

P-value

= 0.473

Method

Normal approximation for two proportions

Parameter type

Risk difference (RD)

Point estimate

5.47

Confidence interval

level

95%

sides

2-sided

lower limit

-9.46

upper limit

20.4

Variability estimate

Standard error of the mean

Dispersion value

7.62

Notes
[18] - The variability estimate standard error of the mean is the standard error of the risk difference.

Analysis of ASAS 40 at Week 8

Statistical analysis description

Week 8

Comparison groups

Tofacitinib 2 mg BID v Placebo BID

Number of subjects included in analysis

103

Analysis specification

Pre-specified

Analysis type

^[19]

P-value

= 0.875

Method

Normal approximation for two proportions

Parameter type

Risk difference (RD)

Point estimate

1.4

Confidence interval

level

95%

sides

2-sided

lower limit

-15.97

upper limit

18.76

Variability estimate

Standard error of the mean

Dispersion value

8.86

Notes
[19] - The variability estimate standard error of the mean is the standard error of the risk difference.

Analysis of ASAS 40 at Week 8

Statistical analysis description

Week 8

Comparison groups

Tofacitinib 5 mg BID v Placebo BID

Number of subjects included in analysis

103

Analysis specification

Pre-specified

Analysis type

^[20]

P-value

= 0.43

Method

Normal approximation for two proportions

Parameter type

Risk difference (RD)

Point estimate

7.16

Confidence interval

level

95%

sides

2-sided

lower limit

-10.65

upper limit

24.97

Variability estimate

Standard error of the mean

Dispersion value

9.09

Notes
[20] - The variability estimate standard error of the mean is the standard error of the risk difference.

Analysis of ASAS 40 at Week 8

Statistical analysis description

Week 8

Comparison groups

Tofacitinib 10 mg BID v Placebo BID

Number of subjects included in analysis

103

Analysis specification

Pre-specified

Analysis type

^[21]

P-value

= 0.32

Method

Normal approximation for two proportions

Parameter type

Risk difference (RD)

Point estimate

9.09

Confidence interval

level

95%

sides

2-sided

lower limit

-8.84

upper limit

27.01

Variability estimate

Standard error of the mean

Dispersion value

9.15

Notes
[21] - The variability estimate standard error of the mean is the standard error of the risk difference.

Analysis of ASAS 40 at Week 12

Statistical analysis description

Week 12

Comparison groups

Tofacitinib 2 mg BID v Placebo BID

Number of subjects included in analysis

103

Analysis specification

Pre-specified

Analysis type

^[22]

P-value

= 0.01

Method

Normal approximation for two proportions

Parameter type

Risk difference (RD)

Point estimate

22.7

Confidence interval

level

95%

sides

2-sided

lower limit

5.41

upper limit

39.99

Variability estimate

Standard error of the mean

Dispersion value

8.82

Notes
[22] - The variability estimate standard error of the mean is the standard error of the risk difference.

Analysis of ASAS 40 at Week 12

Statistical analysis description

Week 12

Comparison groups

Tofacitinib 5 mg BID v Placebo BID

Number of subjects included in analysis

103

Analysis specification

Pre-specified

Analysis type

^[23]

P-value

= 0.003

Method

Normal approximation for two proportions

Parameter type

Risk difference (RD)

Point estimate

26.55

Confidence interval

level

95%

sides

2-sided

lower limit

9.16

upper limit

43.93

Variability estimate

Standard error of the mean

Dispersion value

8.87

Notes
[23] - The variability estimate standard error of the mean is the standard error of the risk difference.

Analysis of ASAS 40 at Week 12

Statistical analysis description

Week 12

Comparison groups

Tofacitinib 10 mg BID v Placebo BID

Number of subjects included in analysis

103

Analysis specification

Pre-specified

Analysis type

^[24]

P-value

= 0.031

Method

Normal approximation for two proportions

Parameter type

Risk difference (RD)

Point estimate

18.85

Confidence interval

level

95%

sides

2-sided

lower limit

1.72

upper limit

35.99

Variability estimate

Standard error of the mean

Dispersion value

8.74

Notes
[24] - The variability estimate standard error of the mean is the standard error of the risk difference.

Secondary: Percentage of Participants Achieving ASAS5/6 Response at Weeks 2, 4, 8 and 12

Top of page

End point title

Percentage of Participants Achieving ASAS5/6 Response at Weeks 2, 4, 8 and 12

End point description

ASAS5/6 consists of 6 domains: the 4 used in ASAS20 (Patient's Global Assessment of Disease Activity, spinal pain, function, inflammation plus spinal mobility and an acute phase reactant, C Reactive Protein (CRP). ASAS 5/6 is defined as ≥20% improvement in at least 5 domains and no worsening in the remaining domain. Missing data were handled by NRI/LOCF. Analysis population is the FAS, n is the number of responders at each visit.

End point type

Secondary

End point timeframe

Baseline, Week 2, Week 4, Week 8, Week 12

End point values	Tofacitinib 2 mg BID	Tofacitinib 5 mg BID	Tofacitinib 10 mg BID	Placebo BID
Number of subjects analysed	52	52	52	51
Units: Percentage of participants
number (not applicable)
Week 2 (n=12, 7, 11, 4)	23.08	13.46	21.15	7.84
Week 4 (n=10, 16, 15, 4)	19.23	30.77	28.85	7.84
Week 8 (n=11, 22, 15, 5)	21.15	42.31	28.85	9.8
Week 12 (n=10, 26, 20, 8)	19.23	50	38.46	15.69

Analysis of ASAS5/6 Response at Week 2

Statistical analysis description

Week 2

Comparison groups

Tofacitinib 2 mg BID v Placebo BID

Number of subjects included in analysis

103

Analysis specification

Pre-specified

Analysis type

^[25]

P-value

= 0.028

Method

Normal approximation for two proportions

Parameter type

Risk difference (RD)

Point estimate

15.23

Confidence interval

level

95%

sides

2-sided

lower limit

1.61

upper limit

28.86

Variability estimate

Standard error of the mean

Dispersion value

6.95

Notes
[25] - The variability estimate standard error of the mean is the standard error of the risk difference.

Analysis of ASAS5/6 Response at Week 2

Statistical analysis description

Week 2

Comparison groups

Tofacitinib 5 mg BID v Placebo BID

Number of subjects included in analysis

103

Analysis specification

Pre-specified

Analysis type

^[26]

P-value

= 0.353

Method

Normal approximation for two proportions

Parameter type

Risk difference (RD)

Point estimate

5.62

Confidence interval

level

95%

sides

2-sided

lower limit

-6.23

upper limit

17.47

Variability estimate

Standard error of the mean

Dispersion value

6.05

Notes
[26] - The variability estimate standard error of the mean is the standard error of the risk difference.

Analysis of ASAS5/6 Response at Week 2

Statistical analysis description

Week 2

Comparison groups

Tofacitinib 10 mg BID v Placebo BID

Number of subjects included in analysis

103

Analysis specification

Pre-specified

Analysis type

^[27]

P-value

= 0.05

Method

Normal approximation for two proportions

Parameter type

Risk difference (RD)

Point estimate

13.31

Confidence interval

level

95%

sides

2-sided

lower limit

-0.02

upper limit

26.64

Variability estimate

Standard error of the mean

Dispersion value

6.8

Notes
[27] - The variability estimate standard error of the mean is the standard error of the risk difference.

Analysis of ASAS5/6 Response at Week 4

Statistical analysis description

Week 4

Comparison groups

Tofacitinib 2 mg BID v Placebo BID

Number of subjects included in analysis

103

Analysis specification

Pre-specified

Analysis type

^[28]

P-value

= 0.086

Method

Normal approximation for two proportions

Parameter type

Risk difference (RD)

Point estimate

11.39

Confidence interval

level

95%

sides

2-sided

lower limit

-1.62

upper limit

24.39

Variability estimate

Standard error of the mean

Dispersion value

6.64

Notes
[28] - The variability estimate standard error of the mean is the standard error of the risk difference.

Analysis of ASAS5/6 Response at Week 4

Statistical analysis description

Week 4

Comparison groups

Tofacitinib 5 mg BID v Placebo BID

Number of subjects included in analysis

103

Analysis specification

Pre-specified

Analysis type

^[29]

P-value

= 0.002

Method

Normal approximation for two proportions

Parameter type

Risk difference (RD)

Point estimate

22.93

Confidence interval

level

95%

sides

2-sided

lower limit

8.37

upper limit

37.48

Variability estimate

Standard error of the mean

Dispersion value

7.43

Notes
[29] - The variability estimate standard error of the mean is the standard error of the risk difference.

Analysis of ASAS5/6 Response at Week 4

Statistical analysis description

Week 4

Comparison groups

Tofacitinib 10 mg BID v Placebo BID

Number of subjects included in analysis

103

Analysis specification

Pre-specified

Analysis type

^[30]

P-value

= 0.004

Method

Normal approximation for two proportions

Parameter type

Risk difference (RD)

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

6.65

upper limit

35.36

Variability estimate

Standard error of the mean

Dispersion value

7.32

Notes
[30] - The variability estimate standard error of the mean is the standard error of the risk difference.

Analysis of ASAS5/6 Response at Week 8

Statistical analysis description

Week 8

Comparison groups

Tofacitinib 2 mg BID v Placebo BID

Number of subjects included in analysis

103

Analysis specification

Pre-specified

Analysis type

^[31]

P-value

= 0.106

Method

Normal approximation for two proportions

Parameter type

Risk difference (RD)

Point estimate

11.35

Confidence interval

level

95%

sides

2-sided

lower limit

-2.43

upper limit

25.13

Variability estimate

Standard error of the mean

Dispersion value

7.03

Notes
[31] - The variability estimate standard error of the mean is the standard error of the risk difference.

Analysis of ASAS5/6 Response at Week 8

Statistical analysis description

Week 8

Comparison groups

Tofacitinib 5 mg BID v Placebo BID

Number of subjects included in analysis

103

Analysis specification

Pre-specified

Analysis type

^[32]

P-value

< 0.001

Method

Normal approximation for two proportions

Parameter type

Risk difference (RD)

Point estimate

32.5

Confidence interval

level

95%

sides

2-sided

lower limit

16.79

upper limit

48.22

Variability estimate

Standard error of the mean

Dispersion value

8.02

Notes
[32] - The variability estimate standard error of the mean is the standard error of the risk difference.

Analysis of ASAS5/6 Response at Week 8

Statistical analysis description

Week 8

Comparison groups

Tofacitinib 10 mg BID v Placebo BID

Number of subjects included in analysis

103

Analysis specification

Pre-specified

Analysis type

^[33]

P-value

= 0.012

Method

Normal approximation for two proportions

Parameter type

Risk difference (RD)

Point estimate

19.04

Confidence interval

level

95%

sides

2-sided

lower limit

4.27

upper limit

33.81

Variability estimate

Standard error of the mean

Dispersion value

7.54

Notes
[33] - The variability estimate standard error of the mean is the standard error of the risk difference.

Analysis of ASAS5/6 Response at Week 12

Statistical analysis description

Week 12

Comparison groups

Tofacitinib 2 mg BID v Placebo BID

Number of subjects included in analysis

103

Analysis specification

Pre-specified

Analysis type

^[34]

P-value

= 0.635

Method

Normal approximation for two proportions

Parameter type

Risk difference (RD)

Point estimate

3.54

Confidence interval

level

95%

sides

2-sided

lower limit

-11.1

upper limit

18.19

Variability estimate

Standard error of the mean

Dispersion value

7.47

Notes
[34] - The variability estimate standard error of the mean is the standard error of the risk difference.

Analysis of ASAS5/6 Response at Week 8

Statistical analysis description

Week 12

Comparison groups

Tofacitinib 5 mg BID v Placebo BID

Number of subjects included in analysis

103

Analysis specification

Pre-specified

Analysis type

^[35]

P-value

< 0.001

Method

Normal approximation for two proportions

Parameter type

Risk difference (RD)

Point estimate

34.31

Confidence interval

level

95%

sides

2-sided

lower limit

17.45

upper limit

51.18

Variability estimate

Standard error of the mean

Dispersion value

8.6

Notes
[35] - The variability estimate standard error of the mean is the standard error of the risk difference.

Analysis of ASAS5/6 Response at Week 12

Statistical analysis description

Week 12

Comparison groups

Tofacitinib 10 mg BID v Placebo BID

Number of subjects included in analysis

103

Analysis specification

Pre-specified

Analysis type

^[36]

P-value

= 0.007

Method

Normal approximation for two proportions

Parameter type

Risk difference (RD)

Point estimate

22.78

Confidence interval

level

95%

sides

2-sided

lower limit

6.21

upper limit

39.34

Variability estimate

Standard error of the mean

Dispersion value

8.45

Notes
[36] - The variability estimate standard error of the mean is the standard error of the risk difference.

Secondary: Change from Baseline of Ankylosing Spondylitis Disease Activity Score using C-Reactive Protein ASDAS(CRP) at Weeks 2, 4, 8 and 12

Top of page

End point title

Change from Baseline of Ankylosing Spondylitis Disease Activity Score using C-Reactive Protein ASDAS(CRP) at Weeks 2, 4, 8 and 12

End point description

The ASDAS(CRP) is a derived score that uses back pain, duration of morning stiffness, Patient's Global Assessment of their disease and peripheral pain/swelling. The formula used for calculating the ASDAS(CRP) is 0.12 x Back Pain + 0.06 x Duration of Morning Stiffness + 0.11 x Patient Global + 0.07 x Peripheral Pain/Swelling + 0.58 x Ln(CRP+1). The calculated score can be from 0 to no defined upper limit. A negative number indicates a reduction in the score which indicates decrease in disease activity. Analysis population is the FAS, when change from baseline is analysed FAS requires that participants have a baseline and at least one post-baseline measurement.

End point type

Secondary

End point timeframe

Baseline, Week 2, Week 4, Week 8, Week 12

End point values	Tofacitinib 2 mg BID	Tofacitinib 5 mg BID	Tofacitinib 10 mg BID	Placebo BID
Number of subjects analysed	51	51	51	50
Units: Units on a scale
least squares mean (standard error)
Week 2	-0.68 ( 0.096 )	-1 ( 0.096 )	-0.97 ( 0.096 )	-0.5 ( 0.097 )
Week 4	-1.01 ( 0.099 )	-1.2 ( 0.099 )	-1.17 ( 0.099 )	-0.58 ( 0.1 )
Week 8	-1.08 ( 0.111 )	-1.36 ( 0.111 )	-1.32 ( 0.112 )	-0.73 ( 0.112 )
Week 12	-1.23 ( 0.119 )	-1.41 ( 0.119 )	-1.37 ( 0.121 )	-0.68 ( 0.123 )

Analysis of ASDAS(CRP) at Week 2

Statistical analysis description

Week 2

Comparison groups

Tofacitinib 2 mg BID v Placebo BID

Number of subjects included in analysis

101

Analysis specification

Pre-specified

Analysis type

^[37]

P-value

= 0.175

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.19

Confidence interval

level

95%

sides

2-sided

lower limit

-0.46

upper limit

0.08

Variability estimate

Standard error of the mean

Dispersion value

0.136

Notes
[37] - Includes fixed effects of treatment group, visit, and treatment-group by-visit interaction and baseline value, using an unstructured covariance matrix.

Analysis of ASDAS(CRP) at Week 2

Statistical analysis description

Week 2

Comparison groups

Tofacitinib 5 mg BID v Placebo BID

Number of subjects included in analysis

101

Analysis specification

Pre-specified

Analysis type

^[38]

P-value

< 0.001

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.51

Confidence interval

level

95%

sides

2-sided

lower limit

-0.77

upper limit

-0.24

Variability estimate

Standard error of the mean

Dispersion value

0.136

Notes
[38] - Includes fixed effects of treatment group, visit, and treatment-group by-visit interaction and baseline value, using an unstructured covariance matrix.

Analysis of ASDAS(CRP) at Week 2

Statistical analysis description

Week 2

Comparison groups

Tofacitinib 10 mg BID v Placebo BID

Number of subjects included in analysis

101

Analysis specification

Pre-specified

Analysis type

^[39]

P-value

< 0.001

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.47

Confidence interval

level

95%

sides

2-sided

lower limit

-0.74

upper limit

-0.2

Variability estimate

Standard error of the mean

Dispersion value

0.136

Notes
[39] - Includes fixed effects of treatment group, visit, and treatment-group by-visit interaction and baseline value, using an unstructured covariance matrix.

Analysis of ASDAS(CRP) at Week 4

Statistical analysis description

Week 4

Comparison groups

Tofacitinib 2 mg BID v Placebo BID

Number of subjects included in analysis

101

Analysis specification

Pre-specified

Analysis type

^[40]

P-value

= 0.003

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.43

Confidence interval

level

95%

sides

2-sided

lower limit

-0.7

upper limit

-0.15

Variability estimate

Standard error of the mean

Dispersion value

0.141

Notes
[40] - Includes fixed effects of treatment group, visit, and treatment-group by-visit interaction and baseline value, using an unstructured covariance matrix.

Analysis of ASDAS(CRP) at Week 4

Statistical analysis description

Week 4

Comparison groups

Tofacitinib 5 mg BID v Placebo BID

Number of subjects included in analysis

101

Analysis specification

Pre-specified

Analysis type

^[41]

P-value

< 0.001

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.62

Confidence interval

level

95%

sides

2-sided

lower limit

-0.9

upper limit

-0.34

Variability estimate

Standard error of the mean

Dispersion value

0.141

Notes
[41] - Includes fixed effects of treatment group, visit, and treatment-group by-visit interaction and baseline value, using an unstructured covariance matrix.

Analysis of ASDAS(CRP) at Week 4

Statistical analysis description

Week 4

Comparison groups

Tofacitinib 10 mg BID v Placebo BID

Number of subjects included in analysis

101

Analysis specification

Pre-specified

Analysis type

^[42]

P-value

< 0.001

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.59

Confidence interval

level

95%

sides

2-sided

lower limit

-0.86

upper limit

-0.31

Variability estimate

Standard error of the mean

Dispersion value

0.141

Notes
[42] - Includes fixed effects of treatment group, visit, and treatment-group by-visit interaction and baseline value, using an unstructured covariance matrix.

Analysis of ASDAS(CRP) at Week 8

Statistical analysis description

Week 8

Comparison groups

Tofacitinib 2 mg BID v Placebo BID

Number of subjects included in analysis

101

Analysis specification

Pre-specified

Analysis type

^[43]

P-value

= 0.026

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.35

Confidence interval

level

95%

sides

2-sided

lower limit

-0.66

upper limit

-0.04

Variability estimate

Standard error of the mean

Dispersion value

0.158

Notes
[43] - Includes fixed effects of treatment group, visit, and treatment-group by-visit interaction and baseline value, using an unstructured covariance matrix.

Analysis of ASDAS(CRP) at Week 8

Statistical analysis description

Week 8

Comparison groups

Tofacitinib 5 mg BID v Placebo BID

Number of subjects included in analysis

101

Analysis specification

Pre-specified

Analysis type

^[44]

P-value

< 0.001

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.63

Confidence interval

level

95%

sides

2-sided

lower limit

-0.94

upper limit

-0.32

Variability estimate

Standard error of the mean

Dispersion value

0.157

Notes
[44] - Includes fixed effects of treatment group, visit, and treatment-group by-visit interaction and baseline value, using an unstructured covariance matrix.

Analysis of ASDAS(CRP) at Week 8

Statistical analysis description

Week 8

Comparison groups

Tofacitinib 10 mg BID v Placebo BID

Number of subjects included in analysis

101

Analysis specification

Pre-specified

Analysis type

^[45]

P-value

< 0.001

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.59

Confidence interval

level

95%

sides

2-sided

lower limit

-0.9

upper limit

-0.27

Variability estimate

Standard error of the mean

Dispersion value

0.159

Notes
[45] - Includes fixed effects of treatment group, visit, and treatment-group by-visit interaction and baseline value, using an unstructured covariance matrix.

Analysis of ASDAS(CRP) at Week 12

Statistical analysis description

Week 12

Comparison groups

Tofacitinib 2 mg BID v Placebo BID

Number of subjects included in analysis

101

Analysis specification

Pre-specified

Analysis type

^[46]

P-value

= 0.002

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.55

Confidence interval

level

95%

sides

2-sided

lower limit

-0.89

upper limit

-0.21

Variability estimate

Standard error of the mean

Dispersion value

0.171

Notes
[46] - Includes fixed effects of treatment group, visit, and treatment-group by-visit interaction and baseline value, using an unstructured covariance matrix.

Analysis of ASDAS(CRP) at Week 12

Statistical analysis description

Week 12

Comparison groups

Tofacitinib 5 mg BID v Placebo BID

Number of subjects included in analysis

101

Analysis specification

Pre-specified

Analysis type

^[47]

P-value

< 0.001

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.73

Confidence interval

level

95%

sides

2-sided

lower limit

-1.07

upper limit

-0.39

Variability estimate

Standard error of the mean

Dispersion value

0.171

Notes
[47] - Includes fixed effects of treatment group, visit, and treatment-group by-visit interaction and baseline value, using an unstructured covariance matrix.

Analysis of ASDAS(CRP) at Week 12

Statistical analysis description

Week 12

Comparison groups

Tofacitinib 10 mg BID v Placebo BID

Number of subjects included in analysis

101

Analysis specification

Pre-specified

Analysis type

^[48]

P-value

< 0.001

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.69

Confidence interval

level

95%

sides

2-sided

lower limit

-1.03

upper limit

-0.35

Variability estimate

Standard error of the mean

Dispersion value

0.172

Notes
[48] - Includes fixed effects of treatment group, visit, and treatment-group by-visit interaction and baseline value, using an unstructured covariance matrix.

Secondary: Percentage of Participants with ASDAS Clinically Important Improvement at Weeks 2, 4, 8 and 12

Top of page

End point title

Percentage of Participants with ASDAS Clinically Important Improvement at Weeks 2, 4, 8 and 12

End point description

The ASDAS clinically important improvement was calculated from the ASDAS data. The ASDAS clinically important improvement is defined as change (decrease) from baseline of ≥1.1 units. Missing data were handled by NRI/LOCF. Analysis population is the FAS, n is the number of responders at each visit.

End point type

Secondary

End point timeframe

Baseline, Week 2, Week 4, Week 8, Week 12

End point values	Tofacitinib 2 mg BID	Tofacitinib 5 mg BID	Tofacitinib 10 mg BID	Placebo BID
Number of subjects analysed	52	52	52	51
Units: Percentage of participants
number (not applicable)
Week 2 (n=14, 25, 21, 8)	26.92	48.08	40.38	15.69
Week4 (n=22, 30, 27, 10)	42.31	57.69	51.92	19.61
Week 8 (n=23, 31, 31, 15)	44.23	59.62	59.62	29.41
Week 12 (n=27, 33, 29, 14)	51.92	63.46	55.77	27.45

Analysis of ASDAS Improvement at Week 2

Statistical analysis description

Week 2

Comparison groups

Tofacitinib 2 mg BID v Placebo BID

Number of subjects included in analysis

103

Analysis specification

Pre-specified

Analysis type

^[49]

P-value

= 0.159

Method

Normal approximation for two proportions

Parameter type

Risk difference (RD)

Point estimate

11.24

Confidence interval

level

95%

sides

2-sided

lower limit

-4.41

upper limit

26.89

Variability estimate

Standard error of the mean

Dispersion value

7.99

Notes
[49] - The variability estimate standard error of the mean is the standard error of the risk difference.

Analysis of ASDAS Improvement at Week 2

Statistical analysis description

Week 2

Comparison groups

Tofacitinib 5 mg BID v Placebo BID

Number of subjects included in analysis

103

Analysis specification

Pre-specified

Analysis type

^[50]

P-value

< 0.001

Method

Normal approximation for two proportions

Parameter type

Risk difference (RD)

Point estimate

32.39

Confidence interval

level

95%

sides

2-sided

lower limit

15.54

upper limit

49.24

Variability estimate

Standard error of the mean

Dispersion value

8.6

Notes
[50] - The variability estimate standard error of the mean is the standard error of the risk difference.

Analysis of ASDAS Improvement at Week 2

Statistical analysis description

Week 2

Comparison groups

Tofacitinib 10 mg BID v Placebo BID

Number of subjects included in analysis

103

Analysis specification

Pre-specified

Analysis type

^[51]

P-value

= 0.004

Method

Normal approximation for two proportions

Parameter type

Risk difference (RD)

Point estimate

24.7

Confidence interval

level

95%

sides

2-sided

lower limit

8.04

upper limit

41.36

Variability estimate

Standard error of the mean

Dispersion value

8.5

Notes
[51] - The variability estimate standard error of the mean is the standard error of the risk difference.

Analysis of ASDAS Improvement at Week 4

Statistical analysis description

Week 4

Comparison groups

Tofacitinib 2 mg BID v Placebo BID

Number of subjects included in analysis

103

Analysis specification

Pre-specified

Analysis type

^[52]

P-value

= 0.01

Method

Normal approximation for two proportions

Parameter type

Risk difference (RD)

Point estimate

22.7

Confidence interval

level

95%

sides

2-sided

lower limit

5.41

upper limit

39.99

Variability estimate

Standard error of the mean

Dispersion value

8.82

Notes
[52] - The variability estimate standard error of the mean is the standard error of the risk difference.

Analysis of ASDAS Improvement at Week 4

Statistical analysis description

Week 4

Comparison groups

Tofacitinib 5 mg BID v Placebo BID

Number of subjects included in analysis

103

Analysis specification

Pre-specified

Analysis type

^[53]

P-value

< 0.001

Method

Normal approximation for two proportions

Parameter type

Risk difference (RD)

Point estimate

38.08

Confidence interval

level

95%

sides

2-sided

lower limit

20.79

upper limit

55.38

Variability estimate

Standard error of the mean

Dispersion value

8.82

Notes
[53] - The variability estimate standard error of the mean is the standard error of the risk difference.

Analysis of ASDAS Improvement at Week 4

Statistical analysis description

Week 4

Comparison groups

Tofacitinib 10 mg BID v Placebo BID

Number of subjects included in analysis

103

Analysis specification

Pre-specified

Analysis type

^[54]

P-value

< 0.001

Method

Normal approximation for two proportions

Parameter type

Risk difference (RD)

Point estimate

32.32

Confidence interval

level

95%

sides

2-sided

lower limit

14.9

upper limit

49.73

Variability estimate

Standard error of the mean

Dispersion value

8.88

Notes
[54] - The variability estimate standard error of the mean is the standard error of the risk difference.

Analysis of ASDAS Improvement at Week 8

Statistical analysis description

Week 8

Comparison groups

Tofacitinib 2 mg BID v Placebo BID

Number of subjects included in analysis

103

Analysis specification

Pre-specified

Analysis type

^[55]

P-value

= 0.114

Method

Normal approximation for two proportions

Parameter type

Risk difference (RD)

Point estimate

14.82

Confidence interval

level

95%

sides

2-sided

lower limit

-3.58

upper limit

33.22

Variability estimate

Standard error of the mean

Dispersion value

9.39

Notes
[55] - The variability estimate standard error of the mean is the standard error of the risk difference.

Analysis of ASDAS Improvement at Week 8

Statistical analysis description

Week 8

Comparison groups

Tofacitinib 5 mg BID v Placebo BID

Number of subjects included in analysis

103

Analysis specification

Pre-specified

Analysis type

^[56]

P-value

= 0.001

Method

Normal approximation for two proportions

Parameter type

Risk difference (RD)

Point estimate

30.2

Confidence interval

level

95%

sides

2-sided

lower limit

11.92

upper limit

48.49

Variability estimate

Standard error of the mean

Dispersion value

9.33

Notes
[56] - The variability estimate standard error of the mean is the standard error of the risk difference.

Analysis of ASDAS Improvement at Week 8

Statistical analysis description

Week 8

Comparison groups

Tofacitinib 10 mg BID v Placebo BID

Number of subjects included in analysis

103

Analysis specification

Pre-specified

Analysis type

^[57]

P-value

= 0.001

Method

Normal approximation for two proportions

Parameter type

Risk difference (RD)

Point estimate

30.2

Confidence interval

level

95%

sides

2-sided

lower limit

11.92

upper limit

48.49

Variability estimate

Standard error of the mean

Dispersion value

9.33

Notes
[57] - The variability estimate standard error of the mean is the standard error of the risk difference.

Analysis of ASDAS Improvement at Week 12

Statistical analysis description

Week 12

Comparison groups

Tofacitinib 2 mg BID v Placebo BID

Number of subjects included in analysis

103

Analysis specification

Pre-specified

Analysis type

^[58]

P-value

= 0.009

Method

Normal approximation for two proportions

Parameter type

Risk difference (RD)

Point estimate

24.47

Confidence interval

level

95%

sides

2-sided

lower limit

6.18

upper limit

42.76

Variability estimate

Standard error of the mean

Dispersion value

9.33

Notes
[58] - The variability estimate standard error of the mean is the standard error of the risk difference.

Analysis of ASDAS Improvement at Week 12

Statistical analysis description

Week 12

Comparison groups

Tofacitinib 5 mg BID v Placebo BID

Number of subjects included in analysis

103

Analysis specification

Pre-specified

Analysis type

^[59]

P-value

< 0.001

Method

Normal approximation for two proportions

Parameter type

Risk difference (RD)

Point estimate

36.01

Confidence interval

level

95%

sides

2-sided

lower limit

18.09

upper limit

53.94

Variability estimate

Standard error of the mean

Dispersion value

9.15

Notes
[59] - The variability estimate standard error of the mean is the standard error of the risk difference.

Analysis of ASDAS Improvement at Week 12

Statistical analysis description

Week 12

Comparison groups

Tofacitinib 10 mg BID v Placebo BID

Number of subjects included in analysis

103

Analysis specification

Pre-specified

Analysis type

^[60]

P-value

= 0.002

Method

Normal approximation for two proportions

Parameter type

Risk difference (RD)

Point estimate

28.32

Confidence interval

level

95%

sides

2-sided

lower limit

10.09

upper limit

46.55

Variability estimate

Standard error of the mean

Dispersion value

9.3

Notes
[60] - The variability estimate standard error of the mean is the standard error of the risk difference.

Secondary: Percentage of Participants with ASDAS Major Improvement at Weeks 2, 4, 8 and 12

Top of page

End point title

Percentage of Participants with ASDAS Major Improvement at Weeks 2, 4, 8 and 12

End point description

The ASDAS major improvement was calculated from the ASDAS data. The ASDAS major improvement was defined as change (decrease) from baseline of ≥2.0 units. Missing data were handled by NRI/LOCF. Analysis population is the FAS, n is the number of responders at each visit.

End point type

Secondary

End point timeframe

Baseline, Week 2, Week 4, Week 8, Week 12

End point values	Tofacitinib 2 mg BID	Tofacitinib 5 mg BID	Tofacitinib 10 mg BID	Placebo BID
Number of subjects analysed	52	52	52	51
Units: Percentage of participants
number (not applicable)
Week 2 (n=4, 4, 4, 1)	7.69	7.69	7.69	1.96
Week 4 (n=6, 6, 8, 3)	11.54	11.54	15.38	5.88
Week 8 (n=6, 14, 12, 5)	11.54	26.92	23.08	9.8
Week 12 (n=10, 12, 13, 6)	19.23	23.08	25	11.76

Analysis of ASDAS Major Improvement at Week 2

Statistical analysis description

Week 2

Comparison groups

Tofacitinib 2 mg BID v Placebo BID

Number of subjects included in analysis

103

Analysis specification

Pre-specified

Analysis type

^[61]

P-value

= 0.17

Method

Normal approximation for two proportions

Parameter type

Risk difference (RD)

Point estimate

5.73

Confidence interval

level

95%

sides

2-sided

lower limit

-2.45

upper limit

13.91

Variability estimate

Standard error of the mean

Dispersion value

4.17

Notes
[61] - The variability estimate standard error of the mean is the standard error of the risk difference.

Analysis of ASDAS Major Improvement at Week 2

Statistical analysis description

Week 2

Comparison groups

Tofacitinib 5 mg BID v Placebo BID

Number of subjects included in analysis

103

Analysis specification

Pre-specified

Analysis type

^[62]

P-value

= 0.17

Method

Normal approximation for two proportions

Parameter type

Risk difference (RD)

Point estimate

5.73

Confidence interval

level

95%

sides

2-sided

lower limit

-2.45

upper limit

13.91

Variability estimate

Standard error of the mean

Dispersion value

4.17

Notes
[62] - The variability estimate standard error of the mean is the standard error of the risk difference.

Analysis of ASDAS Major Improvement at Week 2

Statistical analysis description

Week 2

Comparison groups

Tofacitinib 10 mg BID v Placebo BID

Number of subjects included in analysis

103

Analysis specification

Pre-specified

Analysis type

^[63]

P-value

= 0.17

Method

Normal approximation for two proportions

Parameter type

Risk difference (RD)

Point estimate

5.73

Confidence interval

level

95%

sides

2-sided

lower limit

-2.45

upper limit

13.91

Variability estimate

Standard error of the mean

Dispersion value

4.17

Notes
[63] - The variability estimate standard error of the mean is the standard error of the risk difference.

Analysis of ASDAS Major Improvement at Week 4

Statistical analysis description

Week 4

Comparison groups

Tofacitinib 2 mg BID v Placebo BID

Number of subjects included in analysis

103

Analysis specification

Pre-specified

Analysis type

^[64]

P-value

= 0.306

Method

Normal approximation for two proportions

Parameter type

Risk difference (RD)

Point estimate

5.66

Confidence interval

level

95%

sides

2-sided

lower limit

-5.17

upper limit

16.48

Variability estimate

Standard error of the mean

Dispersion value

5.52

Notes
[64] - The variability estimate standard error of the mean is the standard error of the risk difference.

Analysis of ASDAS Major Improvement at Week 4

Statistical analysis description

Week 4

Comparison groups

Tofacitinib 5 mg BID v Placebo BID

Number of subjects included in analysis

103

Analysis specification

Pre-specified

Analysis type

^[65]

P-value

= 0.306

Method

Normal approximation for two proportions

Parameter type

Risk difference (RD)

Point estimate

5.66

Confidence interval

level

95%

sides

2-sided

lower limit

-5.17

upper limit

16.48

Variability estimate

Standard error of the mean

Dispersion value

5.52

Notes
[65] - The variability estimate standard error of the mean is the standard error of the risk difference.

Analysis of ASDAS Major Improvement at Week 4

Statistical analysis description

Week 4

Comparison groups

Tofacitinib 10 mg BID v Placebo BID

Number of subjects included in analysis

103

Analysis specification

Pre-specified

Analysis type

^[66]

P-value

= 0.113

Method

Normal approximation for two proportions

Parameter type

Risk difference (RD)

Point estimate

9.5

Confidence interval

level

95%

sides

2-sided

lower limit

-2.24

upper limit

21.24

Variability estimate

Standard error of the mean

Dispersion value

5.99

Notes
[66] - The variability estimate standard error of the mean is the standard error of the risk difference.

Analysis of ASDAS Major Improvement at Week 8

Statistical analysis description

Week 8

Comparison groups

Tofacitinib 2 mg BID v Placebo BID

Number of subjects included in analysis

103

Analysis specification

Pre-specified

Analysis type

^[67]

P-value

= 0.775

Method

Normal approximation for two proportions

Parameter type

Risk difference (RD)

Point estimate

1.73

Confidence interval

level

95%

sides

2-sided

lower limit

-10.18

upper limit

13.65

Variability estimate

Standard error of the mean

Dispersion value

6.08

Notes
[67] - The variability estimate standard error of the mean is the standard error of the risk difference.

Analysis of ASDAS Major Improvement at Week 8

Statistical analysis description

Week 8

Comparison groups

Tofacitinib 5 mg BID v Placebo BID

Number of subjects included in analysis

103

Analysis specification

Pre-specified

Analysis type

^[68]

P-value

= 0.021

Method

Normal approximation for two proportions

Parameter type

Risk difference (RD)

Point estimate

17.12

Confidence interval

level

95%

sides

2-sided

lower limit

2.56

upper limit

31.68

Variability estimate

Standard error of the mean

Dispersion value

7.43

Notes
[68] - The variability estimate standard error of the mean is the standard error of the risk difference.

Analysis of ASDAS Major Improvement at Week 8

Statistical analysis description

Week 8

Comparison groups

Tofacitinib 10 mg BID v Placebo BID

Number of subjects included in analysis

103

Analysis specification

Pre-specified

Analysis type

^[69]

P-value

= 0.064

Method

Normal approximation for two proportions

Parameter type

Risk difference (RD)

Point estimate

13.27

Confidence interval

level

95%

sides

2-sided

lower limit

-0.79

upper limit

27.34

Variability estimate

Standard error of the mean

Dispersion value

7.17

Notes
[69] - The variability estimate standard error of the mean is the standard error of the risk difference.

Analysis of ASDAS Major Improvement at Week 12

Statistical analysis description

Week 12

Comparison groups

Tofacitinib 2 mg BID v Placebo BID

Number of subjects included in analysis

103

Analysis specification

Pre-specified

Analysis type

^[70]

P-value

= 0.292

Method

Normal approximation for two proportions

Parameter type

Risk difference (RD)

Point estimate

7.47

Confidence interval

level

95%

sides

2-sided

lower limit

-6.42

upper limit

21.36

Variability estimate

Standard error of the mean

Dispersion value

7.09

Notes
[70] - The variability estimate standard error of the mean is the standard error of the risk difference.

Analysis of ASDAS Major Improvement at Week 12

Statistical analysis description

Week 12

Comparison groups

Tofacitinib 5 mg BID v Placebo BID

Number of subjects included in analysis

103

Analysis specification

Pre-specified

Analysis type

^[71]

P-value

= 0.125

Method

Normal approximation for two proportions

Parameter type

Risk difference (RD)

Point estimate

11.31

Confidence interval

level

95%

sides

2-sided

lower limit

-3.16

upper limit

25.78

Variability estimate

Standard error of the mean

Dispersion value

7.38

Notes
[71] - The variability estimate standard error of the mean is the standard error of the risk difference.

Analysis of ASDAS Major Improvement at Week 12

Statistical analysis description

Week 12

Comparison groups

Tofacitinib 10 mg BID v Placebo BID

Number of subjects included in analysis

103

Analysis specification

Pre-specified

Analysis type

^[72]

P-value

= 0.078

Method

Normal approximation for two proportions

Parameter type

Risk difference (RD)

Point estimate

13.24

Confidence interval

level

95%

sides

2-sided

lower limit

-1.49

upper limit

27.96

Variability estimate

Standard error of the mean

Dispersion value

7.51

Notes
[72] - The variability estimate standard error of the mean is the standard error of the risk difference.

Secondary: Percentage of Participants Achieving ASDAS Inactive Disease at Weeks 2, 4, 8 and 12

Top of page

End point title

Percentage of Participants Achieving ASDAS Inactive Disease at Weeks 2, 4, 8 and 12

End point description

The ASDAS inactive disease was calculated from the ASDAS data. The ASDAS inactive disease was defined as ASDAS <1.3 units. Missing data were handled by NRI/LOCF. Analysis population is the FAS, n is the number of responders at each visit.

End point type

Secondary

End point timeframe

Baseline, Week 2, Week 4, Week 8, Week 12

End point values	Tofacitinib 2 mg BID	Tofacitinib 5 mg BID	Tofacitinib 10 mg BID	Placebo BID
Number of subjects analysed	52	52	52	51
Units: Percentage of participants
number (not applicable)
Week 2 (n=1, 1, 1, 0)	1.92	1.92	1.92	0
Week 4 (n=1, 3, 4, 1)	1.92	5.77	7.69	1.96
Week 8 (n=3, 1, 5, 1)	5.77	1.92	9.62	1.96
Week 12 (n=7, 7, 8, 4)	13.46	13.46	15.38	7.84

Analysis of ASDAS Inactive Disease at Week 2

Statistical analysis description

Week 2

Comparison groups

Tofacitinib 2 mg BID v Placebo BID

Number of subjects included in analysis

103

Analysis specification

Pre-specified

Analysis type

^[73]

P-value

= 0.313

Method

Normal approximation for two proportions

Parameter type

Risk difference (RD)

Point estimate

1.92

Confidence interval

level

95%

sides

2-sided

lower limit

-1.81

upper limit

5.66

Variability estimate

Standard error of the mean

Dispersion value

1.9

Notes
[73] - The variability estimate standard error of the mean is the standard error of the risk difference.

Analysis of ASDAS Inactive Disease at Week 2

Statistical analysis description

Week 2

Comparison groups

Tofacitinib 5 mg BID v Placebo BID

Number of subjects included in analysis

103

Analysis specification

Pre-specified

Analysis type

^[74]

P-value

= 0.313

Method

Normal approximation for two proportions

Parameter type

Risk difference (RD)

Point estimate

1.92

Confidence interval

level

95%

sides

2-sided

lower limit

-1.81

upper limit

5.66

Variability estimate

Standard error of the mean

Dispersion value

1.9

Notes
[74] - The variability estimate standard error of the mean is the standard error of the risk difference.

Analysis of ASDAS Inactive Disease at Week 2

Statistical analysis description

Week 2

Comparison groups

Tofacitinib 10 mg BID v Placebo BID

Number of subjects included in analysis

103

Analysis specification

Pre-specified

Analysis type

^[75]

P-value

= 0.313

Method

Normal approximation for two proportions

Parameter type

Risk difference (RD)

Point estimate

1.92

Confidence interval

level

95%

sides

2-sided

lower limit

-1.81

upper limit

5.66

Variability estimate

Standard error of the mean

Dispersion value

1.9

Notes
[75] - The variability estimate standard error of the mean is the standard error of the risk difference.

Analysis of ASDAS Inactive Disease at Week 4

Statistical analysis description

Week 4

Comparison groups

Tofacitinib 2 mg BID v Placebo BID

Number of subjects included in analysis

103

Analysis specification

Pre-specified

Analysis type

^[76]

P-value

= 0.989

Method

Normal approximation for two proportions

Parameter type

Risk difference (RD)

Point estimate

-0.04

Confidence interval

level

95%

sides

2-sided

lower limit

-5.37

upper limit

5.29

Variability estimate

Standard error of the mean

Dispersion value

2.72

Notes
[76] - The variability estimate standard error of the mean is the standard error of the risk difference.

Analysis of ASDAS Inactive Disease at Week 4

Statistical analysis description

Week 4

Comparison groups

Tofacitinib 5 mg BID v Placebo BID

Number of subjects included in analysis

103

Analysis specification

Pre-specified

Analysis type

^[77]

P-value

= 0.313

Method

Normal approximation for two proportions

Parameter type

Risk difference (RD)

Point estimate

3.81

Confidence interval

level

95%

sides

2-sided

lower limit

-3.58

upper limit

11.2

Variability estimate

Standard error of the mean

Dispersion value

3.77

Notes
[77] - The variability estimate standard error of the mean is the standard error of the risk difference.

Analysis of ASDAS Inactive Disease at Week 4

Statistical analysis description

Week 4

Comparison groups

Tofacitinib 10 mg BID v Placebo BID

Number of subjects included in analysis

103

Analysis specification

Pre-specified

Analysis type

^[78]

P-value

= 0.17

Method

Normal approximation for two proportions

Parameter type

Risk difference (RD)

Point estimate

5.73

Confidence interval

level

95%

sides

2-sided

lower limit

-2.45

upper limit

13.91

Variability estimate

Standard error of the mean

Dispersion value

4.17

Notes
[78] - The variability estimate standard error of the mean is the standard error of the risk difference.

Analysis of ASDAS Inactive Disease at Week 8

Statistical analysis description

Week 8

Comparison groups

Tofacitinib 2 mg BID v Placebo BID

Number of subjects included in analysis

103

Analysis specification

Pre-specified

Analysis type

^[79]

P-value

= 0.313

Method

Normal approximation for two proportions

Parameter type

Risk difference (RD)

Point estimate

3.81

Confidence interval

level

95%

sides

2-sided

lower limit

-3.58

upper limit

11.2

Variability estimate

Standard error of the mean

Dispersion value

3.77

Notes
[79] - The variability estimate standard error of the mean is the standard error of the risk difference.

Analysis of ASDAS Inactive Disease at Week 8

Statistical analysis description

Week 8

Comparison groups

Tofacitinib 5 mg BID v Placebo BID

Number of subjects included in analysis

103

Analysis specification

Pre-specified

Analysis type

^[80]

P-value

= 0.989

Method

Normal approximation for two proportions

Parameter type

Mean difference (final values)

Point estimate

-0.04

Confidence interval

level

95%

sides

2-sided

lower limit

-5.37

upper limit

5.29

Variability estimate

Standard error of the mean

Dispersion value

2.72

Notes
[80] - The variability estimate standard error of the mean is the standard error of the risk difference.

Analysis of ASDAS Inactive Disease at Week 8

Statistical analysis description

Week 8

Comparison groups

Tofacitinib 10 mg BID v Placebo BID

Number of subjects included in analysis

103

Analysis specification

Pre-specified

Analysis type

^[81]

P-value

= 0.091

Method

Normal approximation for two proportions

Parameter type

Risk difference (RD)

Point estimate

7.65

Confidence interval

level

95%

sides

2-sided

lower limit

-1.22

upper limit

16.52

Variability estimate

Standard error of the mean

Dispersion value

4.53

Notes
[81] - The variability estimate standard error of the mean is the standard error of the risk difference.

Analysis of ASDAS Inactive Disease at Week 12

Statistical analysis description

Week 12

Comparison groups

Tofacitinib 2 mg BID v Placebo BID

Number of subjects included in analysis

103

Analysis specification

Pre-specified

Analysis type

^[82]

P-value

= 0.353

Method

Normal approximation for two proportions

Parameter type

Risk difference (RD)

Point estimate

5.62

Confidence interval

level

95%

sides

2-sided

lower limit

-6.23

upper limit

17.47

Variability estimate

Standard error of the mean

Dispersion value

6.05

Notes
[82] - The variability estimate standard error of the mean is the standard error of the risk difference.

Analysis of ASDAS Inactive Disease at Week 12

Statistical analysis description

Week 12

Comparison groups

Tofacitinib 5 mg BID v Placebo BID

Number of subjects included in analysis

103

Analysis specification

Pre-specified

Analysis type

^[83]

P-value

= 0.353

Method

Normal approximation for two proportions

Parameter type

Risk difference (RD)

Point estimate

5.62

Confidence interval

level

95%

sides

2-sided

lower limit

-6.23

upper limit

17.47

Variability estimate

Standard error of the mean

Dispersion value

6.05

Notes
[83] - The variability estimate standard error of the mean is the standard error of the risk difference.

Analysis of ASDAS Inactive Disease at Week 12

Statistical analysis description

Week 12

Comparison groups

Tofacitinib 10 mg BID v Placebo BID

Number of subjects included in analysis

103

Analysis specification

Pre-specified

Analysis type

^[84]

P-value

= 0.228

Method

Normal approximation for two proportions

Parameter type

Risk difference (RD)

Point estimate

7.54

Confidence interval

level

95%

sides

2-sided

lower limit

-4.73

upper limit

19.81

Variability estimate

Standard error of the mean

Dispersion value

6.26

Notes
[84] - The variability estimate standard error of the mean is the standard error of the risk difference.

Secondary: Change from Baseline in BASDAI Total Score at Week 2, 4, 8 and 12

Top of page

End point title

Change from Baseline in BASDAI Total Score at Week 2, 4, 8 and 12

End point description

BASDAI is a validated self-assessment tool used to determine disease activity in participant with Ankylosing Spondylitis. Utilizing a Numerical Rating Scale (NRS) of 0-10 (0 = none and 10 = very severe) participant's answered 6 questions measuring discomfort, pain and fatigue. The BASDAI score is calculated by computing the mean of questions 5 and 6 and adding it to the sum of questions (Q)1-4. This score is then divided by 5. BASDAI=Q1+Q2+Q3+Q4+[Q5+Q6/2]/5. The final BASDAI score averages the individual assessments for a final score range of 0-10. Negative values indicate improvement. Analysis population is the FAS, when change from baseline is analysed FAS requires that participants have a baseline and at least one post-baseline measurement.

End point type

Secondary

End point timeframe

Baseline, Week 2, Week 4, Week 8, Week 12

End point values	Tofacitinib 2 mg BID	Tofacitinib 5 mg BID	Tofacitinib 10 mg BID	Placebo BID
Number of subjects analysed	51	52	51	51
Units: Units on a scale
least squares mean (standard error)
Week 2	-1.45 ( 0.219 )	-1.53 ( 0.217 )	-1.24 ( 0.219 )	-1.42 ( 0.219 )
Week 4	-1.9 ( 0.242 )	-1.93 ( 0.24 )	-1.84 ( 0.242 )	-1.6 ( 0.243 )
Week 8	-2.16 ( 0.268 )	-2.39 ( 0.267 )	-2.35 ( 0.271 )	-1.87 ( 0.271 )
Week 12	-2.75 ( 0.277 )	-2.88 ( 0.276 )	-2.68 ( 0.281 )	-1.85 ( 0.283 )

Analysis of BASDAI Total Score at Week 2

Statistical analysis description

Week 2

Comparison groups

Tofacitinib 2 mg BID v Placebo BID

Number of subjects included in analysis

102

Analysis specification

Pre-specified

Analysis type

^[85]

P-value

= 0.926

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.03

Confidence interval

level

95%

sides

2-sided

lower limit

-0.64

upper limit

0.58

Variability estimate

Standard error of the mean

Dispersion value

0.31

Notes
[85] - Includes fixed effects of treatment group, visit, and treatment-group by-visit interaction and baseline value, using an unstructured covariance matrix.

Analysis of BASDAI Total Score at Week 2

Statistical analysis description

Week 2

Comparison groups

Tofacitinib 5 mg BID v Placebo BID

Number of subjects included in analysis

103

Analysis specification

Pre-specified

Analysis type

^[86]

P-value

= 0.718

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.11

Confidence interval

level

95%

sides

2-sided

lower limit

-0.72

upper limit

0.5

Variability estimate

Standard error of the mean

Dispersion value

0.308

Notes
[86] - Includes fixed effects of treatment group, visit, and treatment-group by-visit interaction and baseline value, using an unstructured covariance matrix.

Analysis of BASDAI Total Score at Week 2

Statistical analysis description

Week 2

Comparison groups

Tofacitinib 10 mg BID v Placebo BID

Number of subjects included in analysis

102

Analysis specification

Pre-specified

Analysis type

^[87]

P-value

= 0.57

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

0.18

Confidence interval

level

95%

sides

2-sided

lower limit

-0.43

upper limit

0.79

Variability estimate

Standard error of the mean

Dispersion value

0.31

Notes
[87] - Includes fixed effects of treatment group, visit, and treatment-group by-visit interaction and baseline value, using an unstructured covariance matrix.

Analysis of BASDAI Total Score at Week 4

Statistical analysis description

Week 4

Comparison groups

Tofacitinib 2 mg BID v Placebo BID

Number of subjects included in analysis

102

Analysis specification

Pre-specified

Analysis type

^[88]

P-value

= 0.384

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.3

Confidence interval

level

95%

sides

2-sided

lower limit

-0.97

upper limit

0.38

Variability estimate

Standard error of the mean

Dispersion value

0.343

Notes
[88] - Includes fixed effects of treatment group, visit, and treatment-group by-visit interaction and baseline value, using an unstructured covariance matrix.

Analysis of BASDAI Total Score at Week 4

Statistical analysis description

Week 4

Comparison groups

Tofacitinib 5 mg BID v Placebo BID

Number of subjects included in analysis

103

Analysis specification

Pre-specified

Analysis type

^[89]

P-value

= 0.334

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.33

Confidence interval

level

95%

sides

2-sided

lower limit

-1

upper limit

0.34

Variability estimate

Standard error of the mean

Dispersion value

0.341

Notes
[89] - Includes fixed effects of treatment group, visit, and treatment-group by-visit interaction and baseline value, using an unstructured covariance matrix.

Analysis of BASDAI Total Score at Week 4

Statistical analysis description

Week 4

Comparison groups

Tofacitinib 10 mg BID v Placebo BID

Number of subjects included in analysis

102

Analysis specification

Pre-specified

Analysis type

^[90]

P-value

= 0.474

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.25

Confidence interval

level

95%

sides

2-sided

lower limit

-0.92

upper limit

0.43

Variability estimate

Standard error of the mean

Dispersion value

0.343

Notes
[90] - Includes fixed effects of treatment group, visit, and treatment-group by-visit interaction and baseline value, using an unstructured covariance matrix.

Analysis of BASDAI Total Score at Week 8

Statistical analysis description

Week 8

Comparison groups

Tofacitinib 2 mg BID v Placebo BID

Number of subjects included in analysis

102

Analysis specification

Pre-specified

Analysis type

^[91]

P-value

= 0.445

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.29

Confidence interval

level

95%

sides

2-sided

lower limit

-1.04

upper limit

0.46

Variability estimate

Standard error of the mean

Dispersion value

0.381

Notes
[91] - Includes fixed effects of treatment group, visit, and treatment-group by-visit interaction and baseline value, using an unstructured covariance matrix.

Analysis of BASDAI Total Score at Week 8

Statistical analysis description

Week 8

Comparison groups

Tofacitinib 5 mg BID v Placebo BID

Number of subjects included in analysis

103

Analysis specification

Pre-specified

Analysis type

^[92]

P-value

= 0.174

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.52

Confidence interval

level

95%

sides

2-sided

lower limit

-1.27

upper limit

0.23

Variability estimate

Standard error of the mean

Dispersion value

0.38

Notes
[92] - Includes fixed effects of treatment group, visit, and treatment-group by-visit interaction and baseline value, using an unstructured covariance matrix.

Analysis of BASDAI Total Score at Week 8

Statistical analysis description

Week 8

Comparison groups

Tofacitinib 10 mg BID v Placebo BID

Number of subjects included in analysis

102

Analysis specification

Pre-specified

Analysis type

^[93]

P-value

= 0.217

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.47

Confidence interval

level

95%

sides

2-sided

lower limit

-1.23

upper limit

0.28

Variability estimate

Standard error of the mean

Dispersion value

0.383

Notes
[93] - Includes fixed effects of treatment group, visit, and treatment-group by-visit interaction and baseline value, using an unstructured covariance matrix.

Analysis of BASDAI Total Score at Week 12

Statistical analysis description

Week 12

Comparison groups

Tofacitinib 2 mg BID v Placebo BID

Number of subjects included in analysis

102

Analysis specification

Pre-specified

Analysis type

^[94]

P-value

= 0.024

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.9

Confidence interval

level

95%

sides

2-sided

lower limit

-1.69

upper limit

-0.12

Variability estimate

Standard error of the mean

Dispersion value

0.396

Notes
[94] - Includes fixed effects of treatment group, visit, and treatment-group by-visit interaction and baseline value, using an unstructured covariance matrix.

Analysis of BASDAI Total Score at Week 12

Statistical analysis description

Week 12

Comparison groups

Tofacitinib 5 mg BID v Placebo BID

Number of subjects included in analysis

103

Analysis specification

Pre-specified

Analysis type

^[95]

P-value

= 0.01

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-1.03

Confidence interval

level

95%

sides

2-sided

lower limit

-1.81

upper limit

-0.24

Variability estimate

Standard error of the mean

Dispersion value

0.396

Notes
[95] - Includes fixed effects of treatment group, visit, and treatment-group by-visit interaction and baseline value, using an unstructured covariance matrix.

Analysis of BASDAI Total Score at Week 12

Statistical analysis description

Week 12

Comparison groups

Tofacitinib 10 mg BID v Placebo BID

Number of subjects included in analysis

102

Analysis specification

Pre-specified

Analysis type

^[96]

P-value

= 0.038

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.83

Confidence interval

level

95%

sides

2-sided

lower limit

-1.62

upper limit

-0.04

Variability estimate

Standard error of the mean

Dispersion value

0.399

Notes
[96] - Includes fixed effects of treatment group, visit, and treatment-group by-visit interaction and baseline value, using an unstructured covariance matrix.

Secondary: Percentage of Participants Achieving a 50% Improvement in BASDAI Response from Baseline (BASDAI 50) at Weeks 2, 4, 8 and 12

Top of page

End point title

Percentage of Participants Achieving a 50% Improvement in BASDAI Response from Baseline (BASDAI 50) at Weeks 2, 4, 8 and 12

End point description

BASDAI is a validated self-assessment tool used to determine disease activity in participant with Ankylosing Spondylitis. Utilizing a NRS of 0-10 (0 = none and 10 = very severe) participant's answered 6 questions measuring discomfort, pain and fatigue. The BASDAI score is calculated by computing the mean of questions 5 and 6 and adding it to the sum of questions (Q)1-4. This score is then divided by 5. The final BASDAI score range from 0-10. A positive response was defined as a 50% improvement in the BASDAI from baseline. Analysis population is the FAS, n is the number of responders at each visit.

End point type

Secondary

End point timeframe

Baseline, Week 2, Week 4, Week 8, Week 12

End point values	Tofacitinib 2 mg BID	Tofacitinib 5 mg BID	Tofacitinib 10 mg BID	Placebo BID
Number of subjects analysed	52	52	52	51
Units: Percentage of participants
number (not applicable)
Week 2 (n=6, 11, 7, 8)	11.54	21.15	13.46	15.69
Week 4 (n=15, 12, 15, 11)	28.85	23.08	28.85	21.57
Week 8 (n=18, 17, 21, 14)	34.62	32.69	40.38	27.45
Week 12 (n=24, 22, 22, 12)	46.15	42.31	42.31	23.53

Analysis of BASDAI 50 at Week 2

Statistical analysis description

Week 2

Comparison groups

Tofacitinib 2 mg BID v Placebo BID

Number of subjects included in analysis

103

Analysis specification

Pre-specified

Analysis type

^[97]

P-value

= 0.539

Method

Normal approximation for two proportions

Parameter type

Risk difference (RD)

Point estimate

-4.15

Confidence interval

level

95%

sides

2-sided

lower limit

-17.38

upper limit

9.08

Variability estimate

Standard error of the mean

Dispersion value

6.75

Notes
[97] - The variability estimate standard error of the mean is the standard error of the risk difference.

Analysis of BASDAI 50 at Week

Statistical analysis description

Week 2

Comparison groups

Tofacitinib 5 mg BID v Placebo BID

Number of subjects included in analysis

103

Analysis specification

Pre-specified

Analysis type

^[98]

P-value

= 0.473

Method

Normal approximation for two proportions

Parameter type

Risk difference (RD)

Point estimate

5.47

Confidence interval

level

95%

sides

2-sided

lower limit

-9.46

upper limit

20.4

Variability estimate

Standard error of the mean

Dispersion value

7.62

Notes
[98] - The variability estimate standard error of the mean is the standard error of the risk difference.

Analysis of BASDAI 50 at Week 2

Statistical analysis description

Week 2

Comparison groups

Tofacitinib 10 mg BID v Placebo BID

Number of subjects included in analysis

103

Analysis specification

Pre-specified

Analysis type

^[99]

P-value

= 0.749

Method

Normal approximation for two proportions

Parameter type

Risk difference (RD)

Point estimate

-2.22

Confidence interval

level

95%

sides

2-sided

lower limit

-15.85

upper limit

11.4

Variability estimate

Standard error of the mean

Dispersion value

6.95

Notes
[99] - The variability estimate standard error of the mean is the standard error of the risk difference.

Analysis of BASDAI 50 at Week

Statistical analysis description

Week 4

Comparison groups

Tofacitinib 2 mg BID v Placebo BID

Number of subjects included in analysis

103

Analysis specification

Pre-specified

Analysis type

^[100]

P-value

= 0.393

Method

Normal approximation for two proportions

Parameter type

Risk difference (RD)

Point estimate

7.28

Confidence interval

level

95%

sides

2-sided

lower limit

-9.43

upper limit

23.98

Variability estimate

Standard error of the mean

Dispersion value

8.52

Notes
[100] - The variability estimate standard error of the mean is the standard error of the risk difference.

Analysis of BASDAI 50 at Week 4

Statistical analysis description

Week 4

Comparison groups

Tofacitinib 5 mg BID v Placebo BID

Number of subjects included in analysis

103

Analysis specification

Pre-specified

Analysis type

^[101]

P-value

= 0.854

Method

Normal approximation for two proportions

Parameter type

Risk difference (RD)

Point estimate

1.51

Confidence interval

level

95%

sides

2-sided

lower limit

-14.57

upper limit

17.59

Variability estimate

Standard error of the mean

Dispersion value

8.2

Notes
[101] - The variability estimate standard error of the mean is the standard error of the risk difference.

Analysis of BASDAI 50 at Week 4

Statistical analysis description

Week 4

Comparison groups

Tofacitinib 10 mg BID v Placebo BID

Number of subjects included in analysis

103

Analysis specification

Pre-specified

Analysis type

^[102]

P-value

= 0.393

Method

Normal approximation for two proportions

Parameter type

Risk difference (RD)

Point estimate

7.28

Confidence interval

level

95%

sides

2-sided

lower limit

-9.43

upper limit

23.98

Variability estimate

Standard error of the mean

Dispersion value

8.52

Notes
[102] - The variability estimate standard error of the mean is the standard error of the risk difference.

Analysis of BASDAI 50 at Week 8

Statistical analysis description

Week 8

Comparison groups

Tofacitinib 2 mg BID v Placebo BID

Number of subjects included in analysis

103

Analysis specification

Pre-specified

Analysis type

^[103]

P-value

= 0.43

Method

Normal approximation for two proportions

Parameter type

Risk difference (RD)

Point estimate

7.16

Confidence interval

level

95%

sides

2-sided

lower limit

-10.65

upper limit

24.97

Variability estimate

Standard error of the mean

Dispersion value

9.09

Notes
[103] - The variability estimate standard error of the mean is the standard error of the risk difference.

Analysis of BASDAI 50 at Week 8

Statistical analysis description

Week 8

Comparison groups

Tofacitinib 5 mg BID v Placebo BID

Number of subjects included in analysis

103

Analysis specification

Pre-specified

Analysis type

^[104]

P-value

= 0.561

Method

Normal approximation for two proportions

Parameter type

Risk difference (RD)

Point estimate

5.24

Confidence interval

level

95%

sides

2-sided

lower limit

-12.44

upper limit

22.92

Variability estimate

Standard error of the mean

Dispersion value

9.02

Notes
[104] - The variability estimate standard error of the mean is the standard error of the risk difference.

Analysis of BASDAI 50 at Week 8

Statistical analysis description

Week 8

Comparison groups

Tofacitinib 10 mg BID v Placebo BID

Number of subjects included in analysis

103

Analysis specification

Pre-specified

Analysis type

^[105]

P-value

= 0.162

Method

Normal approximation for two proportions

Parameter type

Risk difference (RD)

Point estimate

12.93

Confidence interval

level

95%

sides

2-sided

lower limit

-5.17

upper limit

31.04

Variability estimate

Standard error of the mean

Dispersion value

9.24

Notes
[105] - The variability estimate standard error of the mean is the standard error of the risk difference.

Analysis of BASDAI 50 at Week 12

Statistical analysis description

Week 12

Comparison groups

Tofacitinib 2 mg BID v Placebo BID

Number of subjects included in analysis

103

Analysis specification

Pre-specified

Analysis type

^[106]

P-value

= 0.013

Method

Normal approximation for two proportions

Parameter type

Risk difference (RD)

Point estimate

22.62

Confidence interval

level

95%

sides

2-sided

lower limit

4.76

upper limit

40.49

Variability estimate

Standard error of the mean

Dispersion value

9.11

Notes
[106] - The variability estimate standard error of the mean is the standard error of the risk difference.

Analysis of BASDAI 50 at Week 12

Statistical analysis description

Week 12

Comparison groups

Tofacitinib 5 mg BID v Placebo BID

Number of subjects included in analysis

103

Analysis specification

Pre-specified

Analysis type

^[107]

P-value

= 0.038

Method

Normal approximation for two proportions

Parameter type

Risk difference (RD)

Point estimate

18.78

Confidence interval

level

95%

sides

2-sided

lower limit

1.01

upper limit

36.55

Variability estimate

Standard error of the mean

Dispersion value

9.07

Notes
[107] - The variability estimate standard error of the mean is the standard error of the risk difference.

Analysis of BASDAI 50 at Week 12

Statistical analysis description

Week 12

Comparison groups

Tofacitinib 10 mg BID v Placebo BID

Number of subjects included in analysis

103

Analysis specification

Pre-specified

Analysis type

^[108]

P-value

= 0.038

Method

Normal approximation for two proportions

Parameter type

Risk difference (RD)

Point estimate

18.78

Confidence interval

level

95%

sides

2-sided

lower limit

1.01

upper limit

36.55

Variability estimate

Standard error of the mean

Dispersion value

9.07

Notes
[108] - The variability estimate standard error of the mean is the standard error of the risk difference.

Secondary: Change from Baseline in Bath Ankylosing Spondylitis Functional Index (BASFI) at Weeks 2, 4, 8 and 12

Top of page

End point title

Change from Baseline in Bath Ankylosing Spondylitis Functional Index (BASFI) at Weeks 2, 4, 8 and 12

End point description

BASFI is a validated self-assessment tool that determines the degree of physical functional limitation in Ankylosing Spondylitis. Utilizing a NRS of 0-10 (0=easy, 10=impossible), participants answered 10 questions assessing their ability in completing normal daily activities or physically demanding activities. The BASFI score is a mean score of the 10 questions with lower scores indicating better physical function. The higher the negative value the better the improvement. Analysis population is the FAS, when change from baseline is analysed FAS requires that participants have a baseline and at least one post-baseline measurement.

End point type

Secondary

End point timeframe

Baseline, Week 2, Week 4, Week 8, Week 12

End point values	Tofacitinib 2 mg BID	Tofacitinib 5 mg BID	Tofacitinib 10 mg BID	Placebo BID
Number of subjects analysed	51	52	51	51
Units: Units on a scale
least squares mean (standard error)
Week 2	-1.12 ( 0.192 )	-1.16 ( 0.191 )	-0.86 ( 0.192 )	-0.74 ( 0.192 )
Week 4	-1.36 ( 0.21 )	-1.61 ( 0.208 )	-1.32 ( 0.21 )	-1.02 ( 0.21 )
Week 8	-1.61 ( 0.247 )	-2.07 ( 0.246 )	-1.72 ( 0.249 )	-1.38 ( 0.249 )
Week 12	-1.9 ( 0.261 )	-2.39 ( 0.26 )	-2.24 ( 0.264 )	-1.43 ( 0.266 )

Analysis of BASFI at Week 2

Statistical analysis description

Week 2

Comparison groups

Tofacitinib 2 mg BID v Placebo BID

Number of subjects included in analysis

102

Analysis specification

Pre-specified

Analysis type

^[109]

P-value

= 0.164

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.38

Confidence interval

level

95%

sides

2-sided

lower limit

-0.92

upper limit

0.16

Variability estimate

Standard error of the mean

Dispersion value

0.272

Notes
[109] - Includes fixed effects of treatment group, visit, and treatment-group by-visit interaction and baseline value, using an unstructured covariance matrix.

Analysis of BASFI at Week 2

Statistical analysis description

Week 2

Comparison groups

Tofacitinib 5 mg BID v Placebo BID

Number of subjects included in analysis

103

Analysis specification

Pre-specified

Analysis type

^[110]

P-value

= 0.129

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.41

Confidence interval

level

95%

sides

2-sided

lower limit

-0.95

upper limit

0.12

Variability estimate

Standard error of the mean

Dispersion value

0.271

Notes
[110] - Includes fixed effects of treatment group, visit, and treatment-group by-visit interaction and baseline value, using an unstructured covariance matrix.

Analysis of BASFI at Week 2

Statistical analysis description

Week 2

Comparison groups

Tofacitinib 10 mg BID v Placebo BID

Number of subjects included in analysis

102

Analysis specification

Pre-specified

Analysis type

^[111]

P-value

= 0.66

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.12

Confidence interval

level

95%

sides

2-sided

lower limit

-0.66

upper limit

0.42

Variability estimate

Standard error of the mean

Dispersion value

0.272

Notes
[111] - Includes fixed effects of treatment group, visit, and treatment-group by-visit interaction and baseline value, using an unstructured covariance matrix.

Analysis of BASFI at Week 4

Statistical analysis description

Week 4

Comparison groups

Tofacitinib 2 mg BID v Placebo BID

Number of subjects included in analysis

102

Analysis specification

Pre-specified

Analysis type

^[112]

P-value

= 0.256

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.34

Confidence interval

level

95%

sides

2-sided

lower limit

-0.92

upper limit

0.25

Variability estimate

Standard error of the mean

Dispersion value

0.297

Notes
[112] - Includes fixed effects of treatment group, visit, and treatment-group by-visit interaction and baseline value, using an unstructured covariance matrix.

Analysis of BASFI at Week 4

Statistical analysis description

Week 4

Comparison groups

Tofacitinib 5 mg BID v Placebo BID

Number of subjects included in analysis

103

Analysis specification

Pre-specified

Analysis type

^[113]

P-value

= 0.048

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.59

Confidence interval

level

95%

sides

2-sided

lower limit

-1.17

upper limit

Variability estimate

Standard error of the mean

Dispersion value

0.296

Notes
[113] - Includes fixed effects of treatment group, visit, and treatment-group by-visit interaction and baseline value, using an unstructured covariance matrix.

Analysis of BASFI at Week 4

Statistical analysis description

Week 4

Comparison groups

Tofacitinib 10 mg BID v Placebo BID

Number of subjects included in analysis

102

Analysis specification

Pre-specified

Analysis type

^[114]

P-value

= 0.318

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.3

Confidence interval

level

95%

sides

2-sided

lower limit

-0.88

upper limit

0.29

Variability estimate

Standard error of the mean

Dispersion value

0.297

Notes
[114] - Includes fixed effects of treatment group, visit, and treatment-group by-visit interaction and baseline value, using an unstructured covariance matrix.

Analysis of BASFI at Week 8

Statistical analysis description

Week 8

Comparison groups

Tofacitinib 2 mg BID v Placebo BID

Number of subjects included in analysis

102

Analysis specification

Pre-specified

Analysis type

^[115]

P-value

= 0.522

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.22

Confidence interval

level

95%

sides

2-sided

lower limit

-0.92

upper limit

0.47

Variability estimate

Standard error of the mean

Dispersion value

0.35

Notes
[115] - Includes fixed effects of treatment group, visit, and treatment-group by-visit interaction and baseline value, using an unstructured covariance matrix.

Analysis of BASFI at Week 8

Statistical analysis description

Week 8

Comparison groups

Tofacitinib 5 mg BID v Placebo BID

Number of subjects included in analysis

103

Analysis specification

Pre-specified

Analysis type

^[116]

P-value

= 0.05

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.69

Confidence interval

level

95%

sides

2-sided

lower limit

-1.38

upper limit

Variability estimate

Standard error of the mean

Dispersion value

0.35

Notes
[116] - Includes fixed effects of treatment group, visit, and treatment-group by-visit interaction and baseline value, using an unstructured covariance matrix.

Analysis of BASFI at Week 8

Statistical analysis description

Week 8

Comparison groups

Tofacitinib 10 mg BID v Placebo BID

Number of subjects included in analysis

102

Analysis specification

Pre-specified

Analysis type

^[117]

P-value

= 0.337

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.34

Confidence interval

level

95%

sides

2-sided

lower limit

-1.03

upper limit

0.36

Variability estimate

Standard error of the mean

Dispersion value

0.352

Notes
[117] - Includes fixed effects of treatment group, visit, and treatment-group by-visit interaction and baseline value, using an unstructured covariance matrix.

Analysis of BASFI at Week 12

Statistical analysis description

Week 12

Comparison groups

Tofacitinib 2 mg BID v Placebo BID

Number of subjects included in analysis

102

Analysis specification

Pre-specified

Analysis type

^[118]

P-value

= 0.214

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.47

Confidence interval

level

95%

sides

2-sided

lower limit

-1.2

upper limit

0.27

Variability estimate

Standard error of the mean

Dispersion value

0.373

Notes
[118] - Includes fixed effects of treatment group, visit, and treatment-group by-visit interaction and baseline value, using an unstructured covariance matrix.

Analysis of BASFI at Week 12

Statistical analysis description

Week 12

Comparison groups

Tofacitinib 5 mg BID v Placebo BID

Number of subjects included in analysis

103

Analysis specification

Pre-specified

Analysis type

^[119]

P-value

= 0.011

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.96

Confidence interval

level

95%

sides

2-sided

lower limit

-1.69

upper limit

-0.22

Variability estimate

Standard error of the mean

Dispersion value

0.372

Notes
[119] - Includes fixed effects of treatment group, visit, and treatment-group by-visit interaction and baseline value, using an unstructured covariance matrix.

Analysis of BASFI at Week 12

Statistical analysis description

Week 12

Comparison groups

Tofacitinib 10 mg BID v Placebo BID

Number of subjects included in analysis

102

Analysis specification

Pre-specified

Analysis type

^[120]

P-value

= 0.031

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.81

Confidence interval

level

95%

sides

2-sided

lower limit

-1.55

upper limit

-0.08

Variability estimate

Standard error of the mean

Dispersion value

0.375

Notes
[120] - Includes fixed effects of treatment group, visit, and treatment-group by-visit interaction and baseline value, using an unstructured covariance matrix.

Secondary: Change from Baseline in Bath Ankylosing Spondylitis Metrology Index (BASMI) at Weeks 2, 4, 8 and 12

Top of page

End point title

Change from Baseline in Bath Ankylosing Spondylitis Metrology Index (BASMI) at Weeks 2, 4, 8 and 12

End point description

BASMI is an objective measure of spinal mobility and was completed by a blinded assessor. The BASMI score is composed of 5 clinical measures: cervical rotation, intermalleolar distance, modified Schober's test, lateral flexion and tragus to wall distance. The derived score used the average of the 5 assessments on a scale of 0-10 scale with higher scores indicating more impairment of spinal mobility. BASMI was analyzed using the linear function method. The higher the negative value the better the improvement. Analysis population is the FAS, when change from baseline is analysed FAS requires that participants have a baseline and at least one post-baseline measurement.

End point type

Secondary

End point timeframe

Baseline, Week 2, Week 4, Week 8, Week 12

End point values	Tofacitinib 2 mg BID	Tofacitinib 5 mg BID	Tofacitinib 10 mg BID	Placebo BID
Number of subjects analysed	51	51	51	51
Units: Units on a scale
least squares mean (standard error)
Week 2	-0.09 ( 0.075 )	-0.24 ( 0.075 )	-0.22 ( 0.075 )	-0.09 ( 0.075 )
Week 4	-0.15 ( 0.083 )	-0.24 ( 0.083 )	-0.26 ( 0.084 )	-0.14 ( 0.084 )
Week 8	-0.34 ( 0.095 )	-0.4 ( 0.095 )	-0.48 ( 0.096 )	-0.19 ( 0.096 )
Week 12	-0.33 ( 0.109 )	-0.42 ( 0.109 )	-0.55 ( 0.111 )	-0.16 ( 0.112 )

Analysis of BASMI at Week 2

Statistical analysis description

Week 2

Comparison groups

Tofacitinib 2 mg BID v Placebo BID

Number of subjects included in analysis

102

Analysis specification

Pre-specified

Analysis type

^[121]

P-value

= 0.982

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-0.21

upper limit

0.21

Variability estimate

Standard error of the mean

Dispersion value

0.106

Notes
[121] - Includes fixed effects of treatment group, visit, and treatment-group by-visit interaction and baseline value, using an unstructured covariance matrix.

Analysis of BASMI at Week 2

Statistical analysis description

Week 2

Comparison groups

Tofacitinib 5 mg BID v Placebo BID

Number of subjects included in analysis

102

Analysis specification

Pre-specified

Analysis type

^[122]

P-value

= 0.151

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.15

Confidence interval

level

95%

sides

2-sided

lower limit

-0.36

upper limit

0.06

Variability estimate

Standard error of the mean

Dispersion value

0.106

Notes
[122] - Includes fixed effects of treatment group, visit, and treatment-group by-visit interaction and baseline value, using an unstructured covariance matrix.

Analysis of BASMI at Week 2

Statistical analysis description

Week 2

Comparison groups

Tofacitinib 10 mg BID v Placebo BID

Number of subjects included in analysis

102

Analysis specification

Pre-specified

Analysis type

^[123]

P-value

= 0.205

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.13

Confidence interval

level

95%

sides

2-sided

lower limit

-0.34

upper limit

0.07

Variability estimate

Standard error of the mean

Dispersion value

0.106

Notes
[123] - Includes fixed effects of treatment group, visit, and treatment-group by-visit interaction and baseline value, using an unstructured covariance matrix.

Analysis of BASMI at Week 4

Statistical analysis description

Week 4

Comparison groups

Tofacitinib 2 mg BID v Placebo BID

Number of subjects included in analysis

102

Analysis specification

Pre-specified

Analysis type

^[124]

P-value

= 0.898

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

0.22

Variability estimate

Standard error of the mean

Dispersion value

0.118

Notes
[124] - Includes fixed effects of treatment group, visit, and treatment-group by-visit interaction and baseline value, using an unstructured covariance matrix.

Analysis of BASMI at Week 4

Statistical analysis description

Week 4

Comparison groups

Tofacitinib 5 mg BID v Placebo BID

Number of subjects included in analysis

102

Analysis specification

Pre-specified

Analysis type

^[125]

P-value

= 0.37

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.11

Confidence interval

level

95%

sides

2-sided

lower limit

-0.34

upper limit

0.13

Variability estimate

Standard error of the mean

Dispersion value

0.118

Notes
[125] - Includes fixed effects of treatment group, visit, and treatment-group by-visit interaction and baseline value, using an unstructured covariance matrix.

Analysis of BASMI at Week 4

Statistical analysis description

Week 4

Comparison groups

Tofacitinib 10 mg BID v Placebo BID

Number of subjects included in analysis

102

Analysis specification

Pre-specified

Analysis type

^[126]

P-value

= 0.288

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.13

Confidence interval

level

95%

sides

2-sided

lower limit

-0.36

upper limit

0.11

Variability estimate

Standard error of the mean

Dispersion value

0.119

Notes
[126] - Includes fixed effects of treatment group, visit, and treatment-group by-visit interaction and baseline value, using an unstructured covariance matrix.

Analysis of BASMI at Week 8

Statistical analysis description

Week 8

Comparison groups

Tofacitinib 2 mg BID v Placebo BID

Number of subjects included in analysis

102

Analysis specification

Pre-specified

Analysis type

^[127]

P-value

= 0.242

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.16

Confidence interval

level

95%

sides

2-sided

lower limit

-0.42

upper limit

0.11

Variability estimate

Standard error of the mean

Dispersion value

0.135

Notes
[127] - Includes fixed effects of treatment group, visit, and treatment-group by-visit interaction and baseline value, using an unstructured covariance matrix.

Analysis of BASMI at Week 8

Statistical analysis description

Week 8

Comparison groups

Tofacitinib 5 mg BID v Placebo BID

Number of subjects included in analysis

102

Analysis specification

Pre-specified

Analysis type

^[128]

P-value

= 0.12

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.21

Confidence interval

level

95%

sides

2-sided

lower limit

-0.48

upper limit

0.06

Variability estimate

Standard error of the mean

Dispersion value

0.135

Notes
[128] - Includes fixed effects of treatment group, visit, and treatment-group by-visit interaction and baseline value, using an unstructured covariance matrix.

Analysis of BASMI at Week 8

Statistical analysis description

Week 8

Comparison groups

Tofacitinib 10 mg BID v Placebo BID

Number of subjects included in analysis

102

Analysis specification

Pre-specified

Analysis type

^[129]

P-value

= 0.031

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.3

Confidence interval

level

95%

sides

2-sided

lower limit

-0.56

upper limit

-0.03

Variability estimate

Standard error of the mean

Dispersion value

0.136

Notes
[129] - Includes fixed effects of treatment group, visit, and treatment-group by-visit interaction and baseline value, using an unstructured covariance matrix.

Analysis of BASMI at Week 12

Statistical analysis description

Week 12

Comparison groups

Tofacitinib 2 mg BID v Placebo BID

Number of subjects included in analysis

102

Analysis specification

Pre-specified

Analysis type

^[130]

P-value

= 0.28

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.17

Confidence interval

level

95%

sides

2-sided

lower limit

-0.48

upper limit

0.14

Variability estimate

Standard error of the mean

Dispersion value

0.157

Notes
[130] - Includes fixed effects of treatment group, visit, and treatment-group by-visit interaction and baseline value, using an unstructured covariance matrix.

Analysis of BASMI at Week 12

Statistical analysis description

Week 12

Comparison groups

Tofacitinib 5 mg BID v Placebo BID

Number of subjects included in analysis

102

Analysis specification

Pre-specified

Analysis type

^[131]

P-value

= 0.099

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.26

Confidence interval

level

95%

sides

2-sided

lower limit

-0.57

upper limit

0.05

Variability estimate

Standard error of the mean

Dispersion value

0.157

Notes
[131] - Includes fixed effects of treatment group, visit, and treatment-group by-visit interaction and baseline value, using an unstructured covariance matrix.

Analysis of BASMI at Week 12

Statistical analysis description

Week 12

Comparison groups

Tofacitinib 10 mg BID v Placebo BID

Number of subjects included in analysis

102

Analysis specification

Pre-specified

Analysis type

^[132]

P-value

= 0.014

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.39

Confidence interval

level

95%

sides

2-sided

lower limit

-0.7

upper limit

-0.08

Variability estimate

Standard error of the mean

Dispersion value

0.158

Notes
[132] - Includes fixed effects of treatment group, visit, and treatment-group by-visit interaction and baseline value, using an unstructured covariance matrix.

Secondary: Change from Baseline in Maastricht Ankylosing Spondylitis Enthesitis Score (MASES) at Weeks 4, 8 and 12

Top of page

End point title

Change from Baseline in Maastricht Ankylosing Spondylitis Enthesitis Score (MASES) at Weeks 4, 8 and 12

End point description

Assessment of enthesitis of 13 sites was performed in the following, 1st costochondral joint left and right, 7th costochondral joint left and right, posterior superior iliac spine left and right, anterior superior iliac spine left and right, iliac crest left and right, 5th lumbar spinous process and proximal insertion of Achilles tendon left and right. Each site was graded for the presence (1) and absence (0) of tenderness yielding total MASES ranging from 0 (no tenderness) to 13 (worst possible score; severe tenderness).

End point type

Secondary

End point timeframe

Baseline, Week 4, Week 8, Week 12

End point values	Tofacitinib 2 mg BID	Tofacitinib 5 mg BID	Tofacitinib 10 mg BID	Placebo BID
Number of subjects analysed	51	51	50	50
Units: Units on a scale
least squares mean (standard error)
Week 4	-0.16 ( 0.272 )	-0.93 ( 0.271 )	-0.89 ( 0.274 )	-0.11 ( 0.275 )
Week 8	-0.79 ( 0.289 )	-1.19 ( 0.289 )	-0.97 ( 0.295 )	-0.54 ( 0.292 )
Week 12	-0.66 ( 0.259 )	-1.37 ( 0.259 )	-1.24 ( 0.263 )	-0.34 ( 0.265 )

Analysis of MASES at Week 4

Statistical analysis description

Week 4

Comparison groups

Tofacitinib 2 mg BID v Placebo BID

Number of subjects included in analysis

101

Analysis specification

Pre-specified

Analysis type

^[133]

P-value

= 0.895

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.05

Confidence interval

level

95%

sides

2-sided

lower limit

-0.81

upper limit

0.71

Variability estimate

Standard error of the mean

Dispersion value

0.387

Notes
[133] - Includes fixed effects of treatment group, visit, and treatment-group by-visit interaction and baseline value, using an unstructured covariance matrix.

Analysis of MASES at Week 4

Statistical analysis description

Week 4

Comparison groups

Tofacitinib 5 mg BID v Placebo BID

Number of subjects included in analysis

101

Analysis specification

Pre-specified

Analysis type

^[134]

P-value

= 0.033

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.83

Confidence interval

level

95%

sides

2-sided

lower limit

-1.59

upper limit

-0.07

Variability estimate

Standard error of the mean

Dispersion value

0.386

Notes
[134] - Includes fixed effects of treatment group, visit, and treatment-group by-visit interaction and baseline value, using an unstructured covariance matrix.

Analysis of MASES at Week 4

Statistical analysis description

Week 4

Comparison groups

Tofacitinib 10 mg BID v Placebo BID

Number of subjects included in analysis

100

Analysis specification

Pre-specified

Analysis type

^[135]

P-value

= 0.044

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.79

Confidence interval

level

95%

sides

2-sided

lower limit

-1.55

upper limit

-0.02

Variability estimate

Standard error of the mean

Dispersion value

0.388

Notes
[135] - Includes fixed effects of treatment group, visit, and treatment-group by-visit interaction and baseline value, using an unstructured covariance matrix.

Analysis of MASES at Week 8

Statistical analysis description

Week 8

Comparison groups

Tofacitinib 2 mg BID v Placebo BID

Number of subjects included in analysis

101

Analysis specification

Pre-specified

Analysis type

^[136]

P-value

= 0.53

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.26

Confidence interval

level

95%

sides

2-sided

lower limit

-1.07

upper limit

0.55

Variability estimate

Standard error of the mean

Dispersion value

0.411

Notes
[136] - Includes fixed effects of treatment group, visit, and treatment-group by-visit interaction and baseline value, using an unstructured covariance matrix.

Analysis of MASES at Week 8

Statistical analysis description

Week 8

Comparison groups

Tofacitinib 5 mg BID v Placebo BID

Number of subjects included in analysis

101

Analysis specification

Pre-specified

Analysis type

^[137]

P-value

= 0.114

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.65

Confidence interval

level

95%

sides

2-sided

lower limit

-1.46

upper limit

0.16

Variability estimate

Standard error of the mean

Dispersion value

0.411

Notes
[137] - Includes fixed effects of treatment group, visit, and treatment-group by-visit interaction and baseline value, using an unstructured covariance matrix.

Analysis of MASES at Week 8

Statistical analysis description

Week 8

Comparison groups

Tofacitinib 10 mg BID v Placebo BID

Number of subjects included in analysis

100

Analysis specification

Pre-specified

Analysis type

^[138]

P-value

= 0.297

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.43

Confidence interval

level

95%

sides

2-sided

lower limit

-1.25

upper limit

0.38

Variability estimate

Standard error of the mean

Dispersion value

0.415

Notes
[138] - Includes fixed effects of treatment group, visit, and treatment-group by-visit interaction and baseline value, using an unstructured covariance matrix.

Analysis of MASES at Week 12

Statistical analysis description

Week 12

Comparison groups

Tofacitinib 2 mg BID v Placebo BID

Number of subjects included in analysis

101

Analysis specification

Pre-specified

Analysis type

^[139]

P-value

= 0.377

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.33

Confidence interval

level

95%

sides

2-sided

lower limit

-1.06

upper limit

0.4

Variability estimate

Standard error of the mean

Dispersion value

0.37

Notes
[139] - Includes fixed effects of treatment group, visit, and treatment-group by-visit interaction and baseline value, using an unstructured covariance matrix.

Analysis of MASES at Week 12

Statistical analysis description

Week 12

Comparison groups

Tofacitinib 5 mg BID v Placebo BID

Number of subjects included in analysis

101

Analysis specification

Pre-specified

Analysis type

^[140]

P-value

= 0.006

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-1.04

Confidence interval

level

95%

sides

2-sided

lower limit

-1.77

upper limit

-0.31

Variability estimate

Standard error of the mean

Dispersion value

0.37

Notes
[140] - Includes fixed effects of treatment group, visit, and treatment-group by-visit interaction and baseline value, using an unstructured covariance matrix.

Analysis of MASES at Week 12

Statistical analysis description

Week 12

Comparison groups

Tofacitinib 10 mg BID v Placebo BID

Number of subjects included in analysis

100

Analysis specification

Pre-specified

Analysis type

^[141]

P-value

= 0.017

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.9

Confidence interval

level

95%

sides

2-sided

lower limit

-1.64

upper limit

-0.17

Variability estimate

Standard error of the mean

Dispersion value

0.373

Notes
[141] - Includes fixed effects of treatment group, visit, and treatment-group by-visit interaction and baseline value, using an unstructured covariance matrix.

Secondary: Extra-Articular Involvement from Specific Ankylosing Spondylitis Medical History

Top of page

End point title

Extra-Articular Involvement from Specific Ankylosing Spondylitis Medical History

End point description

Participants were assessed at Baseline, Week 12 and Week 16 (Follow-up) to determine if they had specific Ankylosing Spondylitis medical history or changes in specific Ankylosing Spondylitis medical history which included: Inflammatory Bowel Disease (IBD), Peripheral Articular Involvement (PAI; as assessed by swollen joint count), psoriasis (PSO) and uveitis (UVE). n=number of participants completing the Specific Medical History Assessment at each visit.

End point type

Secondary

End point timeframe

Baseline, Week 12 and Follow-up

End point values	Tofacitinib 2 mg BID	Tofacitinib 5 mg BID	Tofacitinib 10 mg BID	Placebo BID
Number of subjects analysed	6	9	6	4
Units: Percentage of Participants
number (not applicable)
IBD: Never: Baseline (n=6, 9, 6, 4)	100	88.9	100	100
IBD: Past But Not Active: Baseline (n=6, 9, 6, 4)	0	0	0	0
IBD: Currently Active: Baseline (n=6, 9, 6, 4)	0	11.1	0	0
IBD: New Condition: Baseline (n=6, 9, 6, 4)	0	0	0	0
IBD: Never: Week 4 (n=4, 7, 3, 2)	100	100	100	100
IBD: Past But Not Active: Week 4 (n=4, 7, 3, 2)	0	0	0	0
IBD: Currently Active: Week 4 (n=4, 7, 3, 2)	0	0	0	0
IBD: New Condition: Week 4 (n=4, 7, 3, 2)	0	0	0	0
IBD: Never: Week 8 (n=2, 6, 2, 4)	100	100	100	100
IBD: Past But Not Active: Week 8 (n=2, 6, 2, 4)	0	0	0	0
IBD: Currently Active: Week 8 (n=2, 6, 2, 4)	0	0	0	0
IBD: New Condition: Week 8 (n=2, 6, 2, 4)	0	0	0	0
IBD: Never: Week 12 (n=5, 6, 2, 3)	100	100	100	100
IBD: Past But Not Active: Week 12 (n=5, 6, 2, 3)	0	0	0	0
IBD: Currently Active: Week 12 (n=5, 6, 2, 3)	0	0	0	0
IBD: New Condition: Week 12 (n=5, 6, 2, 3)	0	0	0	0
IBD: Never: Follow-up (n=3, 6, 4, 2)	100	100	100	100
IBD: Past But Not Active: Follow-up (n=3,6,4,2)	0	0	0	0
IBD: Currently Active: Follow-up (n=3, 6, 4, 2)	0	0	0	0
IBD: New Condition: Follow-up (n=3, 6, 4, 2)	0	0	0	0
PAI: Never: Baseline (n=6, 9, 6, 4)	33.3	44.4	0	25
PAI: Past But Not Active: Baseline (n=6, 9, 6, 4)	0	0	16.7	0
PAI: Currently Active: Baseline (n=6, 9, 6, 4)	66.7	44.4	66.7	75
PAI: New condition: Baseline (n=6, 9, 6, 4)	0	11.1	16.7	0
PAI: Never: Week 4 (n=4, 7, 3, 2)	0	28.6	0	0
PAI: Past But Not Active: Week 4 (n=4, 7, 3, 2)	0	14.3	33.3	0
PAI: Currently Active: Week 4 (n=4, 7, 3, 2)	100	57.1	66.7	100
PAI: New condition: Week 4 (n=4, 7, 3, 2)	0	0	0	0
PAI: Never: Week 8 (n=2, 6, 2, 4)	0	50	0	0
PAI: Past But Not Active: Week 8 (n=2, 6, 2, 4)	0	0	50	0
PAI: Currently Active: Week 8 (n=2, 6, 2, 4)	100	50	50	100
PAI: New Condition: Week 8 (n=2, 6, 2, 4)	0	0	0	0
PAI: Never: Week 12 (n=5, 5, 2, 3)	20	40	0	0
PAI: Past But Not Active: Week 12 (n=5, 5, 2, 3)	0	0	0	0
PAI: Currently Active: Week 12 (n=5, 5, 2, 3)	40	60	100	100
PAI: New Condition: Week 12 (n=5, 5, 2, 3)	40	0	0	0
PAI: Never: Follow-up (n=3, 6, 4, 2)	0	50	25	0
PAI: Past But Not Active: Follow-up (n=3,6,4,2)	0	0	25	0
PAI: Currently Active: Follow-up (n=3, 6, 4, 2)	66.7	50	50	100
PAI: New Condition: Follow-up (n=3, 6, 4, 2)	33.3	0	0	0
PSO: Never: Baseline (n=6, 9, 6, 4)	100	88.9	83.3	75
PSO: Past But Not Active: Baseline (n=6, 9, 6, 4)	0	0	0	0
PSO: Currently Active: Baseline (n=6, 9, 6, 4)	0	11.1	16.7	25
PSO: New Condition: Baseline (n=6, 9, 6, 4)	0	0	0	0
PSO: Never: Week 4 (n=4, 7, 3, 2)	100	85.7	66.7	100
PSO: Past But Not Active: Week 4 (n=4, 7, 3, 2)	0	0	0	0
PSO: Currently Active: Week 4 (n=4, 7, 3, 2)	0	14.3	33.3	0
PSO: New Condition: Week 4 (n=4, 7, 3, 2)	0	0	0	0
PSO: Never: Week 8 (n=2, 6, 2, 4)	100	83.3	50	100
PSO: Past But Not Active: Week 8 (n=2, 6, 2, 4)	0	0	0	0
PSO: Currently Active: Week 8 (n=2, 6, 2, 4)	0	16.7	50	0
PSO: New Condition: Week 8 (n=2, 6, 2, 4)	0	0	0	0
PSO: Never: Week 12 (n=5, 6, 2, 3)	80	83.3	100	100
PSO: Past But Not Active: Week 12 (n=5, 6, 2, 3)	20	0	0	0
PSO: Currently Active: Week 12 (n=5, 6, 2, 3)	0	16.7	0	0
PSO: New Condition: Week 12 (n=5, 6, 2, 3)	0	0	0	0
PSO: Never: Follow-up (n=3, 6, 4, 2)	100	83.3	100	100
PSO: Past But Not Active: Follow-up (n=3,6,4,2)	0	0	0	0
PSO: Currently Active: Follow-up (n=3, 6, 4, 2)	0	16.7	0	0
PSO: New Condition: Follow-up (n=3, 6, 4, 2)	0	0	0	0
UVE: Never: Baseline (n=6, 9, 6, 4)	50	55.6	83.3	100
UVE: Past But Not Active: Baseline (n=6, 9, 6, 4)	16.7	33.3	0	0
UVE: Currently Active: Baseline (n=6, 9, 6, 4)	33.3	11.1	16.7	0
UVE: New Condition: Baseline (n=6, 9, 6, 4)	0	0	0	0
UVE: Never: Week 4 (n=4, 7, 3, 2)	75	71.4	66.7	100
UVE: Past But Not Active: Week 4 (n=4,7,3,2)	25	28.6	33.3	0
UVE: Currently Active: Week 4 (n=4, 7, 3, 2)	0	0	0	0
UVE: New Condition: Week 4 (n=4, 7, 3, 2)	0	0	0	0
UVE: Never: Week 8 (n=2, 6, 2, 4)	100	50	50	100
UVE: Past But Not Active: Week 8 (n=2, 6, 2, 4)	0	50	50	0
UVE: Currenly Active: Week 8 (n=2, 6, 2, 4)	0	0	0	0
UVE: New Condition: Week 8 (n=2, 6, 2, 4)	0	0	0	0
UVE: Never: Week 12 (n=5, 6, 2, 3)	40	66.7	50	100
UVE: Past But Not Active: Week 12 (n=5, 6, 2, 3)	60	33.3	50	0
UVE: Currently Active: Week 12 (n=5, 6, 2, 3)	0	0	0	0
UVE: New Condition: Week 12 (n=5, 6, 2, 3)	0	0	0	0
UVE: Never: Follow-up (n=3, 6, 4, 2)	100	50	50	100
UVE: Past But Not Active: Follow-up (n=3,6,4,2)	0	33.3	25	0
UVE: Currently Active: Follow-up (n=3, 6, 4, 2)	0	16.7	0	0
UVE: New Condition: Follow-up (n=3, 6, 4, 2)	0	0	25	0

No statistical analyses for this end point

Secondary: Change from Baseline of Total Swollen Joint Count at Weeks 2, 4, 8, and 12

Top of page

End point title

Change from Baseline of Total Swollen Joint Count at Weeks 2, 4, 8, and 12

End point description

This assessment was performed by the blinded assessor using the following scale: Present/Absent/Not Done/Not Applicable (to be used for artificial or missing joints) for determination of the total number of swollen joints. Forty-four joints were assessed for swelling on left and right side and included the following: sternoclaviculars, acromioclaviculars, shoulders, elbows, wrists, metacarpophalangeals (I, II, III, IV, V), thumb interphalangeal, proximal interphalangeals (II, III, IV, V), knees, ankles, and metatarsophalangeals (I, II, III, IV, V). Artificial joints were not assessed. A negative change means improvement.

End point type

Secondary

End point timeframe

Baseline, Week 2, Week 4, Week 8, Week 12

End point values	Tofacitinib 2 mg BID	Tofacitinib 5 mg BID	Tofacitinib 10 mg BID	Placebo BID
Number of subjects analysed	51	52	51	51
Units: Units on a scale
least squares mean (standard error)
Week 2	-0.53 ( 0.293 )	0.23 ( 0.291 )	-1.2 ( 0.292 )	-0.43 ( 0.293 )
Week 4	-0.87 ( 0.26 )	-0.57 ( 0.259 )	-1.23 ( 0.26 )	-0.86 ( 0.261 )
Week 8	-1.02 ( 0.442 )	-0.98 ( 0.442 )	-1.28 ( 0.451 )	-0.6 ( 0.448 )
Week 12	-0.87 ( 0.362 )	-0.79 ( 0.362 )	-1.4 ( 0.368 )	-0.99 ( 0.373 )

Analysis of Total Swollen Joint Count at Week 2

Statistical analysis description

Week 2

Comparison groups

Tofacitinib 2 mg BID v Placebo BID

Number of subjects included in analysis

102

Analysis specification

Pre-specified

Analysis type

^[142]

P-value

= 0.8

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.11

Confidence interval

level

95%

sides

2-sided

lower limit

-0.92

upper limit

0.71

Variability estimate

Standard error of the mean

Dispersion value

0.414

Notes
[142] - Includes fixed effects of treatment group, visit, and treatment-group by-visit interaction and baseline value, using an unstructured covariance matrix.

Analysis of Total Swollen Joint Count at Week 2

Statistical analysis description

Week 2

Comparison groups

Tofacitinib 5 mg BID v Placebo BID

Number of subjects included in analysis

103

Analysis specification

Pre-specified

Analysis type

^[143]

P-value

= 0.113

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

0.66

Confidence interval

level

95%

sides

2-sided

lower limit

-0.16

upper limit

1.47

Variability estimate

Standard error of the mean

Dispersion value

0.413

Notes
[143] - Includes fixed effects of treatment group, visit, and treatment-group by-visit interaction and baseline value, using an unstructured covariance matrix.

Analysis of Total Swollen Joint Count at Week 2

Statistical analysis description

Week 2

Comparison groups

Tofacitinib 10 mg BID v Placebo BID

Number of subjects included in analysis

102

Analysis specification

Pre-specified

Analysis type

^[144]

P-value

= 0.064

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.77

Confidence interval

level

95%

sides

2-sided

lower limit

-1.59

upper limit

0.05

Variability estimate

Standard error of the mean

Dispersion value

0.414

Notes
[144] - Includes fixed effects of treatment group, visit, and treatment-group by-visit interaction and baseline value, using an unstructured covariance matrix.

Analysis of Total Swollen Joint Count at Week 4

Statistical analysis description

Week 4

Comparison groups

Tofacitinib 2 mg BID v Placebo BID

Number of subjects included in analysis

102

Analysis specification

Pre-specified

Analysis type

^[145]

P-value

= 0.972

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.01

Confidence interval

level

95%

sides

2-sided

lower limit

-0.74

upper limit

0.71

Variability estimate

Standard error of the mean

Dispersion value

0.368

Notes
[145] - Includes fixed effects of treatment group, visit, and treatment-group by-visit interaction and baseline value, using an unstructured covariance matrix.

Analysis of Total Swollen Joint Count at Week 4

Statistical analysis description

Week 4

Comparison groups

Tofacitinib 5 mg BID v Placebo BID

Number of subjects included in analysis

103

Analysis specification

Pre-specified

Analysis type

^[146]

P-value

= 0.44

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

0.28

Confidence interval

level

95%

sides

2-sided

lower limit

-0.44

upper limit

1.01

Variability estimate

Standard error of the mean

Dispersion value

0.368

Notes
[146] - Includes fixed effects of treatment group, visit, and treatment-group by-visit interaction and baseline value, using an unstructured covariance matrix.

Analysis of Total Swollen Joint Count at Week 4

Statistical analysis description

Week 4

Comparison groups

Tofacitinib 10 mg BID v Placebo BID

Number of subjects included in analysis

102

Analysis specification

Pre-specified

Analysis type

^[147]

P-value

= 0.311

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.37

Confidence interval

level

95%

sides

2-sided

lower limit

-1.1

upper limit

0.35

Variability estimate

Standard error of the mean

Dispersion value

0.369

Notes
[147] - Includes fixed effects of treatment group, visit, and treatment-group by-visit interaction and baseline value, using an unstructured covariance matrix.

Analysis of Total Swollen Joint Count at Week 8

Statistical analysis description

Week 8

Comparison groups

Tofacitinib 2 mg BID v Placebo BID

Number of subjects included in analysis

102

Analysis specification

Pre-specified

Analysis type

^[148]

P-value

= 0.501

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.42

Confidence interval

level

95%

sides

2-sided

lower limit

-1.66

upper limit

0.82

Variability estimate

Standard error of the mean

Dispersion value

0.629

Notes
[148] - Includes fixed effects of treatment group, visit, and treatment-group by-visit interaction and baseline value, using an unstructured covariance matrix.

Analysis of Total Swollen Joint Count at Week 8

Statistical analysis description

Week 8

Comparison groups

Tofacitinib 5 mg BID v Placebo BID

Number of subjects included in analysis

103

Analysis specification

Pre-specified

Analysis type

^[149]

P-value

= 0.543

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.38

Confidence interval

level

95%

sides

2-sided

lower limit

-1.63

upper limit

0.86

Variability estimate

Standard error of the mean

Dispersion value

0.629

Notes
[149] - Includes fixed effects of treatment group, visit, and treatment-group by-visit interaction and baseline value, using an unstructured covariance matrix.

Analysis of Total Swollen Joint Count at Week 8

Statistical analysis description

Week 8

Comparison groups

Tofacitinib 10 mg BID v Placebo BID

Number of subjects included in analysis

102

Analysis specification

Pre-specified

Analysis type

^[150]

P-value

= 0.287

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.68

Confidence interval

level

95%

sides

2-sided

lower limit

-1.93

upper limit

0.57

Variability estimate

Standard error of the mean

Dispersion value

0.636

Notes
[150] - Includes fixed effects of treatment group, visit, and treatment-group by-visit interaction and baseline value, using an unstructured covariance matrix.

Analysis of Total Swollen Joint Count at Week 12

Statistical analysis description

Week 12

Comparison groups

Tofacitinib 2 mg BID v Placebo BID

Number of subjects included in analysis

102

Analysis specification

Pre-specified

Analysis type

^[151]

P-value

= 0.82

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

0.12

Confidence interval

level

95%

sides

2-sided

lower limit

-0.91

upper limit

1.14

Variability estimate

Standard error of the mean

Dispersion value

0.519

Notes
[151] - Includes fixed effects of treatment group, visit, and treatment-group by-visit interaction and baseline value, using an unstructured covariance matrix.

Analysis of Total Swollen Joint Count at Week 12

Statistical analysis description

Week 12

Comparison groups

Tofacitinib 5 mg BID v Placebo BID

Number of subjects included in analysis

103

Analysis specification

Pre-specified

Analysis type

^[152]

P-value

= 0.711

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

0.19

Confidence interval

level

95%

sides

2-sided

lower limit

-0.83

upper limit

1.22

Variability estimate

Standard error of the mean

Dispersion value

0.52

Notes
[152] - Includes fixed effects of treatment group, visit, and treatment-group by-visit interaction and baseline value, using an unstructured covariance matrix.

Analysis of Total Swollen Joint Count at Week 12

Statistical analysis description

Week 12

Comparison groups

Tofacitinib 10 mg BID v Placebo BID

Number of subjects included in analysis

102

Analysis specification

Pre-specified

Analysis type

^[153]

P-value

= 0.424

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.42

Confidence interval

level

95%

sides

2-sided

lower limit

-1.45

upper limit

0.61

Variability estimate

Standard error of the mean

Dispersion value

0.524

Notes
[153] - Includes fixed effects of treatment group, visit, and treatment-group by-visit interaction and baseline value, using an unstructured covariance matrix.

Secondary: Change from Baseline of Mean Spinal Mobility (Chest Expansion) at Week 2, 4, 8 and 12

Top of page

End point title

Change from Baseline of Mean Spinal Mobility (Chest Expansion) at Week 2, 4, 8 and 12

End point description

Chest expansion, measured in centimetres (cm), is defined as the difference in the thoracic circumference during full expiration versus full inspiration. This was measured at the 4th intercostal space. The difference between maximal inspiration and expiration of the two attempts was recorded. The better of the two attempts was used to calculate chest expansion. Missing data at Week 12 were imputed by LOCF if data at an early visit (discontinuation visit) were available.

End point type

Secondary

End point timeframe

Baseline, Week 2, Week 4, Week 8, Week 12

End point values	Tofacitinib 2 mg BID	Tofacitinib 5 mg BID	Tofacitinib 10 mg BID	Placebo BID
Number of subjects analysed	51	51	51	51
Units: Units on a scale
least squares mean (standard error)
Week 2	0.3 ( 0.144 )	0.35 ( 0.143 )	-0.03 ( 0.144 )	0.24 ( 0.144 )
Week 4	0.54 ( 0.164 )	0.13 ( 0.162 )	0.13 ( 0.164 )	0.38 ( 0.165 )
Week 8	0.52 ( 0.178 )	0.35 ( 0.178 )	0.15 ( 0.182 )	0.13 ( 0.181 )
Week 12	0.69 ( 0.187 )	0.49 ( 0.187 )	0.13 ( 0.19 )	0.31 ( 0.193 )

Analysis of Mean Spinal Mobility at Week 2

Statistical analysis description

Week 2

Comparison groups

Tofacitinib 2 mg BID v Placebo BID

Number of subjects included in analysis

102

Analysis specification

Pre-specified

Analysis type

^[154]

P-value

= 0.785

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

0.06

Confidence interval

level

95%

sides

2-sided

lower limit

-0.34

upper limit

0.46

Variability estimate

Standard error of the mean

Dispersion value

0.203

Notes
[154] - Includes fixed effects of treatment group, visit, and treatment-group by-visit interaction and baseline value, using an unstructured covariance matrix.

Analysis of Mean Spinal Mobility at Week 2

Statistical analysis description

Week 2

Comparison groups

Tofacitinib 5 mg BID v Placebo BID

Number of subjects included in analysis

102

Analysis specification

Pre-specified

Analysis type

^[155]

P-value

= 0.605

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

0.11

Confidence interval

level

95%

sides

2-sided

lower limit

-0.3

upper limit

0.51

Variability estimate

Standard error of the mean

Dispersion value

0.203

Notes
[155] - Includes fixed effects of treatment group, visit, and treatment-group by-visit interaction and baseline value, using an unstructured covariance matrix.

Analysis of Mean Spinal Mobility at Week 2

Statistical analysis description

Week 2

Comparison groups

Tofacitinib 10 mg BID v Placebo BID

Number of subjects included in analysis

102

Analysis specification

Pre-specified

Analysis type

^[156]

P-value

= 0.175

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.28

Confidence interval

level

95%

sides

2-sided

lower limit

-0.68

upper limit

0.12

Variability estimate

Standard error of the mean

Dispersion value

0.204

Notes
[156] - Includes fixed effects of treatment group, visit, and treatment-group by-visit interaction and baseline value, using an unstructured covariance matrix.

Analysis of Mean Spinal Mobility at Week 4

Statistical analysis description

Week 4

Comparison groups

Tofacitinib 2 mg BID v Placebo BID

Number of subjects included in analysis

102

Analysis specification

Pre-specified

Analysis type

^[157]

P-value

= 0.482

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

0.16

Confidence interval

level

95%

sides

2-sided

lower limit

-0.29

upper limit

0.62

Variability estimate

Standard error of the mean

Dispersion value

0.232

Notes
[157] - Includes fixed effects of treatment group, visit, and treatment-group by-visit interaction and baseline value, using an unstructured covariance matrix.

Analysis of Mean Spinal Mobility at Week 4

Statistical analysis description

Week 4

Comparison groups

Tofacitinib 5 mg BID v Placebo BID

Number of subjects included in analysis

102

Analysis specification

Pre-specified

Analysis type

^[158]

P-value

= 0.288

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.25

Confidence interval

level

95%

sides

2-sided

lower limit

-0.7

upper limit

0.21

Variability estimate

Standard error of the mean

Dispersion value

0.231

Notes
[158] - Includes fixed effects of treatment group, visit, and treatment-group by-visit interaction and baseline value, using an unstructured covariance matrix.

Analysis of Mean Spinal Mobility at Week 4

Statistical analysis description

Week 4

Comparison groups

Tofacitinib 10 mg BID v Placebo BID

Number of subjects included in analysis

102

Analysis specification

Pre-specified

Analysis type

^[159]

P-value

= 0.278

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.25

Confidence interval

level

95%

sides

2-sided

lower limit

-0.71

upper limit

0.21

Variability estimate

Standard error of the mean

Dispersion value

0.233

Notes
[159] - Includes fixed effects of treatment group, visit, and treatment-group by-visit interaction and baseline value, using an unstructured covariance matrix.

Analysis of Mean Spinal Mobility at Week 8

Statistical analysis description

Week 8

Comparison groups

Tofacitinib 2 mg BID v Placebo BID

Number of subjects included in analysis

102

Analysis specification

Pre-specified

Analysis type

^[160]

P-value

= 0.134

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

0.38

Confidence interval

level

95%

sides

2-sided

lower limit

-0.12

upper limit

0.88

Variability estimate

Standard error of the mean

Dispersion value

0.254

Notes
[160] - Includes fixed effects of treatment group, visit, and treatment-group by-visit interaction and baseline value, using an unstructured covariance matrix.

Analysis of Mean Spinal Mobility at Week 8

Statistical analysis description

Week 8

Comparison groups

Tofacitinib 5 mg BID v Placebo BID

Number of subjects included in analysis

102

Analysis specification

Pre-specified

Analysis type

^[161]

P-value

= 0.397

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

0.22

Confidence interval

level

95%

sides

2-sided

lower limit

-0.29

upper limit

0.72

Variability estimate

Standard error of the mean

Dispersion value

0.254

Notes
[161] - Includes fixed effects of treatment group, visit, and treatment-group by-visit interaction and baseline value, using an unstructured covariance matrix.

Analysis of Mean Spinal Mobility at Week 8

Statistical analysis description

Week 8

Comparison groups

Tofacitinib 10 mg BID v Placebo BID

Number of subjects included in analysis

102

Analysis specification

Pre-specified

Analysis type

^[162]

P-value

= 0.964

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

0.01

Confidence interval

level

95%

sides

2-sided

lower limit

-0.5

upper limit

0.52

Variability estimate

Standard error of the mean

Dispersion value

0.257

Notes
[162] - Includes fixed effects of treatment group, visit, and treatment-group by-visit interaction and baseline value, using an unstructured covariance matrix.

Analysis of Mean Spinal Mobility at Week 12

Statistical analysis description

Week 12

Comparison groups

Tofacitinib 2 mg BID v Placebo BID

Number of subjects included in analysis

102

Analysis specification

Pre-specified

Analysis type

^[163]

P-value

= 0.155

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

0.38

Confidence interval

level

95%

sides

2-sided

lower limit

-0.15

upper limit

0.91

Variability estimate

Standard error of the mean

Dispersion value

0.269

Notes
[163] - Includes fixed effects of treatment group, visit, and treatment-group by-visit interaction and baseline value, using an unstructured covariance matrix.

Analysis of Mean Spinal Mobility at Week 12

Statistical analysis description

Week 12

Comparison groups

Tofacitinib 5 mg BID v Placebo BID

Number of subjects included in analysis

102

Analysis specification

Pre-specified

Analysis type

^[164]

P-value

= 0.491

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

0.19

Confidence interval

level

95%

sides

2-sided

lower limit

-0.34

upper limit

0.72

Variability estimate

Standard error of the mean

Dispersion value

0.269

Notes
[164] - Includes fixed effects of treatment group, visit, and treatment-group by-visit interaction and baseline value, using an unstructured covariance matrix.

Analysis of Mean Spinal Mobility at Week 12

Statistical analysis description

Week 12

Comparison groups

Tofacitinib 10 mg BID v Placebo BID

Number of subjects included in analysis

102

Analysis specification

Pre-specified

Analysis type

^[165]

P-value

= 0.515

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.18

Confidence interval

level

95%

sides

2-sided

lower limit

-0.71

upper limit

0.36

Variability estimate

Standard error of the mean

Dispersion value

0.271

Notes
[165] - Includes fixed effects of treatment group, visit, and treatment-group by-visit interaction and baseline value, using an unstructured covariance matrix.

Secondary: Change from Baseline to Week 12 in Short-Form-36 Health Survey (SF-36) Physical and Mental Health Scores at Week 12

Top of page

End point title

Change from Baseline to Week 12 in Short-Form-36 Health Survey (SF-36) Physical and Mental Health Scores at Week 12

End point description

SF-36 is a standardized survey evaluating 8 aspects of functional health and wellbeing: physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, mental health. The score for a section is an average of the individual question scores, which are scaled 0-100 (0=no functioning, 100=highest level of functioning). Missing data at Week 12 were imputed by LOCF if data at an early visit (discontinuation visit) were available.

End point type

Secondary

End point timeframe

Baseline, Week 12

End point values	Tofacitinib 2 mg BID	Tofacitinib 5 mg BID	Tofacitinib 10 mg BID	Placebo BID
Number of subjects analysed	52	52	52	51
Units: Units on a scale
least squares mean (standard error)
Week 12 Physical Health Score	6.34 ( 0.923 )	6.49 ( 0.914 )	7.05 ( 0.943 )	2.69 ( 0.932 )
Week 12 Mental Health Score	2.08 ( 1.306 )	4.15 ( 1.294 )	3.71 ( 1.336 )	2.41 ( 1.318 )

Analysis of SF-36 Physical Health Score at Week 12

Statistical analysis description

Physical Health Score

Comparison groups

Tofacitinib 2 mg BID v Placebo BID

Number of subjects included in analysis

103

Analysis specification

Pre-specified

Analysis type

^[166]

P-value

= 0.006

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

3.65

Confidence interval

level

95%

sides

2-sided

lower limit

1.06

upper limit

6.24

Variability estimate

Standard error of the mean

Dispersion value

1.312

Notes
[166] - ANCOVA model includes fixed effects for treatment group and baseline value as a covariate.

Analysis of SF-36 Physical Health Score at Week 12

Statistical analysis description

Physical Health Score

Comparison groups

Tofacitinib 5 mg BID v Placebo BID

Number of subjects included in analysis

103

Analysis specification

Pre-specified

Analysis type

^[167]

P-value

= 0.004

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

3.8

Confidence interval

level

95%

sides

2-sided

lower limit

1.23

upper limit

6.37

Variability estimate

Standard error of the mean

Dispersion value

1.305

Notes
[167] - ANCOVA model includes fixed effects for treatment group and baseline value as a covariate.

Analysis of SF-36 Physical Health Score at Week 12

Statistical analysis description

Physical Health Score

Comparison groups

Tofacitinib 10 mg BID v Placebo BID

Number of subjects included in analysis

103

Analysis specification

Pre-specified

Analysis type

^[168]

P-value

= 0.001

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

4.36

Confidence interval

level

95%

sides

2-sided

lower limit

1.74

upper limit

6.98

Variability estimate

Standard error of the mean

Dispersion value

1.328

Notes
[168] - ANCOVA model includes fixed effects for treatment group and baseline value as a covariate.

Analysis of SF-36 Mental Health Score at Week 12

Statistical analysis description

Mental Health Score

Comparison groups

Tofacitinib 2 mg BID v Placebo BID

Number of subjects included in analysis

103

Analysis specification

Pre-specified

Analysis type

^[169]

P-value

= 0.857

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-0.34

Confidence interval

level

95%

sides

2-sided

lower limit

-4

upper limit

3.33

Variability estimate

Standard error of the mean

Dispersion value

1.857

Notes
[169] - ANCOVA model includes fixed effects for treatment group and baseline value as a covariate.

Analysis of SF-36 Mental Health Score at Week 12

Statistical analysis description

Mental Health Score

Comparison groups

Tofacitinib 5 mg BID v Placebo BID

Number of subjects included in analysis

103

Analysis specification

Pre-specified

Analysis type

^[170]

P-value

= 0.35

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

1.73

Confidence interval

level

95%

sides

2-sided

lower limit

-1.91

upper limit

5.37

Variability estimate

Standard error of the mean

Dispersion value

1.848

Notes
[170] - ANCOVA model includes fixed effects for treatment group and baseline value as a covariate.

Analysis of SF-36 Mental Health Score at Week 12

Statistical analysis description

Mental Health Score

Comparison groups

Tofacitinib 10 mg BID v Placebo BID

Number of subjects included in analysis

103

Analysis specification

Pre-specified

Analysis type

^[171]

P-value

= 0.49

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

1.3

Confidence interval

level

95%

sides

2-sided

lower limit

-2.4

upper limit

Variability estimate

Standard error of the mean

Dispersion value

1.876

Notes
[171] - ANCOVA model includes fixed effects for treatment group and baseline value as a covariate.

Secondary: Change from Baseline in EuroQol EQ-5D Health State Profile (EQ-5D) Utility Score at Week 12

Top of page

End point title

Change from Baseline in EuroQol EQ-5D Health State Profile (EQ-5D) Utility Score at Week 12

End point description

EQ-5D: participant rated questionnaire to assess health-related quality of life in terms of single utility score. Health state profile component assesses level of current health for 5 domains: mobility, self-care, usual activities, pain/discomfort and anxiety/depression; Scale range 1 to 3 (1=better health state [no problems], 3=worst health state [confined to bed]).

End point type

Secondary

End point timeframe

Baseline, Week 12

End point values	Tofacitinib 2 mg BID	Tofacitinib 5 mg BID	Tofacitinib 10 mg BID	Placebo BID
Number of subjects analysed	52	52	52	51
Units: Units on a scale
least squares mean (standard error)	0.17 ( 0.034 )	0.16 ( 0.034 )	0.22 ( 0.035 )	0.1 ( 0.034 )

Analysis of EQ-5D Utility Score at Week 12

Comparison groups

Tofacitinib 2 mg BID v Placebo BID

Number of subjects included in analysis

103

Analysis specification

Pre-specified

Analysis type

^[172]

P-value

= 0.125

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

0.07

Confidence interval

level

95%

sides

2-sided

lower limit

-0.02

upper limit

0.17

Variability estimate

Standard error of the mean

Dispersion value

0.048

Notes
[172] - ANCOVA model includes fixed effects for treatment group and baseline value as a covariate.

Analysis of EQ-5D Utility Score at Week 12

Comparison groups

Tofacitinib 5 mg BID v Placebo BID

Number of subjects included in analysis

103

Analysis specification

Pre-specified

Analysis type

^[173]

P-value

= 0.207

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

0.06

Confidence interval

level

95%

sides

2-sided

lower limit

-0.03

upper limit

0.16

Variability estimate

Standard error of the mean

Dispersion value

0.048

Notes
[173] - ANCOVA model includes fixed effects for treatment group and baseline value as a covariate.

Analysis of EQ-5D Utility Score at Week 12

Comparison groups

Tofacitinib 10 mg BID v Placebo BID

Number of subjects included in analysis

103

Analysis specification

Pre-specified

Analysis type

^[174]

P-value

= 0.013

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

0.12

Confidence interval

level

95%

sides

2-sided

lower limit

0.03

upper limit

0.22

Variability estimate

Standard error of the mean

Dispersion value

0.049

Notes
[174] - ANCOVA model includes fixed effects for treatment group and baseline value as a covariate.

Secondary: Change from Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Score at Weeks 2, 4, 8 and 12

Top of page

End point title

Change from Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Score at Weeks 2, 4, 8 and 12

End point description

FACIT-F is a 13-item questionnaire. Participants scored each item on a 5-point scale: 0 (not at all) to 4 (very much). Larger the participant’s response to the questions (with the exception of 2 negatively stated), greater was the participant’s fatigue. For all questions, except for the 2 negatively stated ones, the code was reversed and a new score was calculated as (4 minus the participant’s response). The sum of all responses resulted in the FACIT-Fatigue score for a total possible score of 0 (worse score) to 52 (better score).

End point type

Secondary

End point timeframe

Baseline, Week 2, Week 4, Week 8, Week 12

End point values	Tofacitinib 2 mg BID	Tofacitinib 5 mg BID	Tofacitinib 10 mg BID	Placebo BID
Number of subjects analysed	51	51	51	51
Units: Units on a scale
least squares mean (standard error)
Week 2	3.62 ( 0.871 )	1.97 ( 0.871 )	2.17 ( 0.875 )	1.9 ( 0.872 )
Week 4	4.25 ( 0.931 )	3.67 ( 0.927 )	2.8 ( 0.937 )	2.71 ( 0.938 )
Week 8	4.54 ( 1.039 )	4.81 ( 1.039 )	4.19 ( 1.061 )	2.85 ( 1.053 )
Week 12	4.74 ( 1.145 )	7.03 ( 1.145 )	7.58 ( 1.166 )	3.08 ( 1.178 )

Analysis of FACIT-F Score at Week 2

Statistical analysis description

Week 2

Comparison groups

Tofacitinib 2 mg BID v Placebo BID

Number of subjects included in analysis

102

Analysis specification

Pre-specified

Analysis type

^[175]

P-value

= 0.163

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

1.72

Confidence interval

level

95%

sides

2-sided

lower limit

-0.71

upper limit

4.15

Variability estimate

Standard error of the mean

Dispersion value

1.232

Notes
[175] - Includes fixed effects of treatment group, visit, and treatment-group by-visit interaction and baseline value, using an unstructured covariance matrix.

Analysis of FACIT-F Score at Week 2

Statistical analysis description

Week 2

Comparison groups

Tofacitinib 5 mg BID v Placebo BID

Number of subjects included in analysis

102

Analysis specification

Pre-specified

Analysis type

^[176]

P-value

= 0.955

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

0.07

Confidence interval

level

95%

sides

2-sided

lower limit

-2.36

upper limit

2.5

Variability estimate

Standard error of the mean

Dispersion value

1.232

Notes
[176] - Includes fixed effects of treatment group, visit, and treatment-group by-visit interaction and baseline value, using an unstructured covariance matrix.

Analysis of FACIT-F Score at Week 2

Statistical analysis description

Week 2

Comparison groups

Tofacitinib 10 mg BID v Placebo BID

Number of subjects included in analysis

102

Analysis specification

Pre-specified

Analysis type

^[177]

P-value

= 0.826

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

0.27

Confidence interval

level

95%

sides

2-sided

lower limit

-2.17

upper limit

2.71

Variability estimate

Standard error of the mean

Dispersion value

1.237

Notes
[177] - Includes fixed effects of treatment group, visit, and treatment-group by-visit interaction and baseline value, using an unstructured covariance matrix.

Analysis of FACIT-F Score at Week 4

Statistical analysis description

Week 4

Comparison groups

Tofacitinib 2 mg BID v Placebo BID

Number of subjects included in analysis

102

Analysis specification

Pre-specified

Analysis type

^[178]

P-value

= 0.246

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

1.54

Confidence interval

level

95%

sides

2-sided

lower limit

-1.07

upper limit

4.14

Variability estimate

Standard error of the mean

Dispersion value

1.322

Notes
[178] - Includes fixed effects of treatment group, visit, and treatment-group by-visit interaction and baseline value, using an unstructured covariance matrix.

Analysis of FACIT-F Score at Week 4

Statistical analysis description

Week 4

Comparison groups

Tofacitinib 5 mg BID v Placebo BID

Number of subjects included in analysis

102

Analysis specification

Pre-specified

Analysis type

^[179]

P-value

= 0.467

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

0.96

Confidence interval

level

95%

sides

2-sided

lower limit

-1.64

upper limit

3.56

Variability estimate

Standard error of the mean

Dispersion value

1.318

Notes
[179] - Includes fixed effects of treatment group, visit, and treatment-group by-visit interaction and baseline value, using an unstructured covariance matrix.

Analysis of FACIT-F Score at Week 4

Statistical analysis description

Week 4

Comparison groups

Tofacitinib 10 mg BID v Placebo BID

Number of subjects included in analysis

102

Analysis specification

Pre-specified

Analysis type

^[180]

P-value

= 0.948

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

0.09

Confidence interval

level

95%

sides

2-sided

lower limit

-2.53

upper limit

2.7

Variability estimate

Standard error of the mean

Dispersion value

1.328

Notes
[180] - Includes fixed effects of treatment group, visit, and treatment-group by-visit interaction and baseline value, using an unstructured covariance matrix.

Analysis of FACIT-F Score at Week 8

Statistical analysis description

Week 8

Comparison groups

Tofacitinib 2 mg BID v Placebo BID

Number of subjects included in analysis

102

Analysis specification

Pre-specified

Analysis type

^[181]

P-value

= 0.255

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

1.69

Confidence interval

level

95%

sides

2-sided

lower limit

-1.23

upper limit

4.61

Variability estimate

Standard error of the mean

Dispersion value

1.479

Notes
[181] - Includes fixed effects of treatment group, visit, and treatment-group by-visit interaction and baseline value, using an unstructured covariance matrix.

Analysis of FACIT-F Score at Week 8

Statistical analysis description

Week 8

Comparison groups

Tofacitinib 5 mg BID v Placebo BID

Number of subjects included in analysis

102

Analysis specification

Pre-specified

Analysis type

^[182]

P-value

= 0.187

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

1.96

Confidence interval

level

95%

sides

2-sided

lower limit

-0.96

upper limit

4.87

Variability estimate

Standard error of the mean

Dispersion value

1.479

Notes
[182] - Includes fixed effects of treatment group, visit, and treatment-group by-visit interaction and baseline value, using an unstructured covariance matrix.

Analysis of FACIT-F Score at Week 8

Statistical analysis description

Week 8

Comparison groups

Tofacitinib 10 mg BID v Placebo BID

Number of subjects included in analysis

102

Analysis specification

Pre-specified

Analysis type

^[183]

P-value

= 0.373

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

1.34

Confidence interval

level

95%

sides

2-sided

lower limit

-1.62

upper limit

4.29

Variability estimate

Standard error of the mean

Dispersion value

1.497

Notes
[183] - Includes fixed effects of treatment group, visit, and treatment-group by-visit interaction and baseline value, using an unstructured covariance matrix.

Analysis of FACIT-F Score at Week 12

Statistical analysis description

Week 12

Comparison groups

Tofacitinib 2 mg BID v Placebo BID

Number of subjects included in analysis

102

Analysis specification

Pre-specified

Analysis type

^[184]

P-value

= 0.313

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

1.66

Confidence interval

level

95%

sides

2-sided

lower limit

-1.58

upper limit

4.9

Variability estimate

Standard error of the mean

Dispersion value

1.643

Notes
[184] - Includes fixed effects of treatment group, visit, and treatment-group by-visit interaction and baseline value, using an unstructured covariance matrix.

Analysis of FACIT-F Score at Week 12

Statistical analysis description

Week 12

Comparison groups

Tofacitinib 5 mg BID v Placebo BID

Number of subjects included in analysis

102

Analysis specification

Pre-specified

Analysis type

^[185]

P-value

= 0.017

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

3.95

Confidence interval

level

95%

sides

2-sided

lower limit

0.71

upper limit

7.19

Variability estimate

Standard error of the mean

Dispersion value

1.642

Notes
[185] - Includes fixed effects of treatment group, visit, and treatment-group by-visit interaction and baseline value, using an unstructured covariance matrix.

Analysis of FACIT-F Score at Week 12

Statistical analysis description

Week 12

Comparison groups

Tofacitinib 10 mg BID v Placebo BID

Number of subjects included in analysis

102

Analysis specification

Pre-specified

Analysis type

^[186]

P-value

= 0.007

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

4.51

Confidence interval

level

95%

sides

2-sided

lower limit

1.23

upper limit

7.78

Variability estimate

Standard error of the mean

Dispersion value

1.66

Notes
[186] - Includes fixed effects of treatment group, visit, and treatment-group by-visit interaction and baseline value, using an unstructured covariance matrix.

Adverse events

Top of page

Timeframe for reporting adverse events

From informed consent through and including 28 calendar days after the last administration of the investigational product.

Adverse event reporting additional description

The same event may appear as both an adverse event (AE) and a serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.

Assessment type

Non-systematic

Dictionary name

MedDRA

Dictionary version

18.0

Reporting group title

Tofacitinib 2 mg BID

Reporting group description

Participants were administered 4 tablets (two 1 mg tablets of tofacitinib along with two 5 mg matching placebo tablets) orally BID (in the AM and PM) for a total of 12 weeks.

Reporting group title

Tofacitinib 5 mg BID

Reporting group description

Participants were administered 4 tablets (one 5 mg tablet of tofacitinib, one 5 mg and two 1 mg matching placebo tablets) orally BID (in the AM and PM) for a total of 12 weeks.

Reporting group title

Tofacitinib 10 mg BID

Reporting group description

Participants were administered 4 tablets (two 5 mg tablets of tofacitinib and two 1 mg matching placebo tablets) orally twice a day (in the AM and PM) for a total of 12 weeks.

Reporting group title

Placebo BID

Reporting group description

Participants were administered 4 tablets (two 1 mg placebo tablets and two 5 mg matching placebo tablets) orally twice a day (in the AM and PM) for a total of 12 weeks.

Serious adverse events	Tofacitinib 2 mg BID	Tofacitinib 5 mg BID	Tofacitinib 10 mg BID	Placebo BID
Total subjects affected by serious adverse events
subjects affected / exposed	0 / 52 (0.00%)	1 / 52 (1.92%)	1 / 52 (1.92%)	2 / 51 (3.92%)
number of deaths (all causes)	0	0	0	0
number of deaths resulting from adverse events	0	0	0	0
Injury, poisoning and procedural complications
Tendon injury
subjects affected / exposed	0 / 52 (0.00%)	0 / 52 (0.00%)	1 / 52 (1.92%)	0 / 51 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pregnancy, puerperium and perinatal conditions
Foetal death
subjects affected / exposed ^[1]	0 / 18 (0.00%)	0 / 13 (0.00%)	0 / 14 (0.00%)	1 / 19 (5.26%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Ear and labyrinth disorders
Vertigo
subjects affected / exposed	0 / 52 (0.00%)	0 / 52 (0.00%)	0 / 52 (0.00%)	1 / 51 (1.96%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Eye disorders
Iridocyclitis
subjects affected / exposed	0 / 52 (0.00%)	1 / 52 (1.92%)	0 / 52 (0.00%)	0 / 51 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Reproductive system and breast disorders
Uterine spasm
subjects affected / exposed ^[2]	0 / 18 (0.00%)	0 / 13 (0.00%)	0 / 14 (0.00%)	1 / 19 (5.26%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Vaginal haemorrhage
subjects affected / exposed ^[3]	0 / 18 (0.00%)	0 / 13 (0.00%)	0 / 14 (0.00%)	1 / 19 (5.26%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0

Notes
[1] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
Justification: only female participants were counted as exposed to these adverse events, with the exception of balanoposthitis which only male participants were counted as exposed to.
[2] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
Justification: only female participants were counted as exposed to these adverse events, with the exception of balanoposthitis which only male participants were counted as exposed to.
[3] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
Justification: only female participants were counted as exposed to these adverse events, with the exception of balanoposthitis which only male participants were counted as exposed to.

Frequency threshold for reporting non-serious adverse events: 2%

Non-serious adverse events	Tofacitinib 2 mg BID	Tofacitinib 5 mg BID	Tofacitinib 10 mg BID	Placebo BID
Total subjects affected by non serious adverse events
subjects affected / exposed	15 / 52 (28.85%)	10 / 52 (19.23%)	13 / 52 (25.00%)	14 / 51 (27.45%)
Investigations
Alanine aminotransferase increased
subjects affected / exposed	1 / 52 (1.92%)	2 / 52 (3.85%)	0 / 52 (0.00%)	0 / 51 (0.00%)
occurrences all number	1	2	0	0
Blood creatine phosphokinase increased
subjects affected / exposed	0 / 52 (0.00%)	2 / 52 (3.85%)	1 / 52 (1.92%)	1 / 51 (1.96%)
occurrences all number	0	2	1	1
Injury, poisoning and procedural complications
Ligament sprain
subjects affected / exposed	0 / 52 (0.00%)	0 / 52 (0.00%)	2 / 52 (3.85%)	0 / 51 (0.00%)
occurrences all number	0	0	2	0
Nervous system disorders
Dizziness
subjects affected / exposed	0 / 52 (0.00%)	0 / 52 (0.00%)	0 / 52 (0.00%)	2 / 51 (3.92%)
occurrences all number	0	0	0	2
Headache
subjects affected / exposed	2 / 52 (3.85%)	2 / 52 (3.85%)	2 / 52 (3.85%)	1 / 51 (1.96%)
occurrences all number	2	2	2	1
Pregnancy, puerperium and perinatal conditions
Pregnancy
subjects affected / exposed ^[4]	0 / 18 (0.00%)	0 / 13 (0.00%)	0 / 14 (0.00%)	1 / 19 (5.26%)
occurrences all number	0	0	0	1
Gastrointestinal disorders
Abdominal pain upper
subjects affected / exposed	3 / 52 (5.77%)	0 / 52 (0.00%)	2 / 52 (3.85%)	1 / 51 (1.96%)
occurrences all number	3	0	2	1
Diarrhoea
subjects affected / exposed	2 / 52 (3.85%)	1 / 52 (1.92%)	0 / 52 (0.00%)	1 / 51 (1.96%)
occurrences all number	3	1	0	1
Mouth ulceration
subjects affected / exposed	2 / 52 (3.85%)	0 / 52 (0.00%)	0 / 52 (0.00%)	1 / 51 (1.96%)
occurrences all number	2	0	0	1
Reproductive system and breast disorders
Balanoposthitis
subjects affected / exposed ^[5]	1 / 34 (2.94%)	0 / 39 (0.00%)	0 / 38 (0.00%)	0 / 32 (0.00%)
occurrences all number	1	0	0	0
Skin and subcutaneous tissue disorders
Rash
subjects affected / exposed	1 / 52 (1.92%)	0 / 52 (0.00%)	0 / 52 (0.00%)	2 / 51 (3.92%)
occurrences all number	1	0	0	2
Renal and urinary disorders
Haematuria
subjects affected / exposed	0 / 52 (0.00%)	1 / 52 (1.92%)	2 / 52 (3.85%)	1 / 51 (1.96%)
occurrences all number	0	1	2	1
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	1 / 52 (1.92%)	2 / 52 (3.85%)	0 / 52 (0.00%)	0 / 51 (0.00%)
occurrences all number	1	3	0	0
Infections and infestations
Bronchitis
subjects affected / exposed	0 / 52 (0.00%)	0 / 52 (0.00%)	1 / 52 (1.92%)	2 / 51 (3.92%)
occurrences all number	0	0	1	2
Nasopharyngitis
subjects affected / exposed	4 / 52 (7.69%)	4 / 52 (7.69%)	2 / 52 (3.85%)	3 / 51 (5.88%)
occurrences all number	4	4	2	3
Upper respiratory tract infection
subjects affected / exposed	4 / 52 (7.69%)	0 / 52 (0.00%)	3 / 52 (5.77%)	1 / 51 (1.96%)
occurrences all number	5	0	3	1
Vaginitis bacterial
subjects affected / exposed ^[6]	0 / 18 (0.00%)	0 / 13 (0.00%)	0 / 14 (0.00%)	1 / 19 (5.26%)
occurrences all number	0	0	0	1
Vulvovaginal mycotic infection
subjects affected / exposed ^[7]	1 / 18 (5.56%)	0 / 13 (0.00%)	0 / 14 (0.00%)	0 / 19 (0.00%)
occurrences all number	1	0	0	0

Notes
[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: only female participants were counted as exposed to these adverse events, with the exception of balanoposthitis which only male participants were counted as exposed to.
[5] - 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: only female participants were counted as exposed to these adverse events, with the exception of balanoposthitis which only male participants were counted as exposed to.
[6] - 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: only female participants were counted as exposed to these adverse events, with the exception of balanoposthitis which only male participants were counted as exposed to.
[7] - 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: only female participants were counted as exposed to these adverse events, with the exception of balanoposthitis which only male participants were counted as exposed to.

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Were there any global substantial amendments to the protocol? Yes

15 Apr 2013

Description: Clarification of and updates to some inclusion and exclusion criteria. Addition of opportunistic infections to the discontinuation criteria and clarification of when an investigator could discontinue a participant in the event of serious or severe AEs. New sponsor standard wording providing clarity on the method of access to the sponsor Qualified Medical Personnel and medical coverage. Clarification of total blood draw volume anticipated during the study. Section on retained pharmacogenomics samples (banked biospecimens) and markers of drug response was updated. Clarification of SAE reporting requirements for protocol specified SAEs. Additional AE sections related to infections. Updates to communication of results by Pfizer.

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, Randomized, Double-Blind, Placebo-Controlled, Dose-Ranging Study of the Efficacy and Safety of Tofacitinib in Subjects with Active Ankylosing Spondylitis (AS)

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Percentage of Participants Achieving 20 Percent (%) Improvement in Assessment of SpondyloArthritis International Society (ASAS) Score (ASAS 20) at Week 12

Primary: Percentage of Participants Achieving 20 Percent (%) Improvement in Assessment of SpondyloArthritis International Society (ASAS) Score (ASAS 20) at Week 12

Primary: Percentage of Participants Achieving ASAS20 at Week 12

Primary: Percentage of Participants Achieving ASAS20 at Week 12

Secondary: Percentage of Participants Achieving 20% Improvement in ASAS Score at Weeks 2, 4 and 8

Secondary: Percentage of Participants Achieving 20% Improvement in ASAS Score at Weeks 2, 4 and 8

Secondary: Change from Baseline in Spondyloarthritis Research Consortium of Canada (SPARCC) Magnetic Resonance Imaging (MRI) Index of Disease Activity Score of the Sacroiliac (SI) Joints at Week 12

Secondary: Change from Baseline in Spondyloarthritis Research Consortium of Canada (SPARCC) Magnetic Resonance Imaging (MRI) Index of Disease Activity Score of the Sacroiliac (SI) Joints at Week 12

Secondary: Change from Baseline in SPARCC MRI Index of Disease Activity Score of the Spine at Week 12

Secondary: Change from Baseline in SPARCC MRI Index of Disease Activity Score of the Spine at Week 12

Secondary: Change from Baseline in Modified Berlin Ankylosing Spondylitis Spine Magnetic Resonance Imaging Activity Score (ASspiMRI) of the Spine at Week 12

Secondary: Change from Baseline in Modified Berlin Ankylosing Spondylitis Spine Magnetic Resonance Imaging Activity Score (ASspiMRI) of the Spine at Week 12

Secondary: Percentage of Participants Achieving 40% Improvement in ASAS score at weeks 2, 4, 8 and 12

Secondary: Percentage of Participants Achieving 40% Improvement in ASAS score at weeks 2, 4, 8 and 12

Secondary: Percentage of Participants Achieving ASAS5/6 Response at Weeks 2, 4, 8 and 12

Secondary: Percentage of Participants Achieving ASAS5/6 Response at Weeks 2, 4, 8 and 12

Secondary: Change from Baseline of Ankylosing Spondylitis Disease Activity Score using C-Reactive Protein ASDAS(CRP) at Weeks 2, 4, 8 and 12

Secondary: Change from Baseline of Ankylosing Spondylitis Disease Activity Score using C-Reactive Protein ASDAS(CRP) at Weeks 2, 4, 8 and 12

Secondary: Percentage of Participants with ASDAS Clinically Important Improvement at Weeks 2, 4, 8 and 12

Secondary: Percentage of Participants with ASDAS Clinically Important Improvement at Weeks 2, 4, 8 and 12

Secondary: Percentage of Participants with ASDAS Major Improvement at Weeks 2, 4, 8 and 12

Secondary: Percentage of Participants with ASDAS Major Improvement at Weeks 2, 4, 8 and 12

Secondary: Percentage of Participants Achieving ASDAS Inactive Disease at Weeks 2, 4, 8 and 12

Secondary: Percentage of Participants Achieving ASDAS Inactive Disease at Weeks 2, 4, 8 and 12

Secondary: Change from Baseline in BASDAI Total Score at Week 2, 4, 8 and 12

Secondary: Change from Baseline in BASDAI Total Score at Week 2, 4, 8 and 12

Secondary: Percentage of Participants Achieving a 50% Improvement in BASDAI Response from Baseline (BASDAI 50) at Weeks 2, 4, 8 and 12

Secondary: Percentage of Participants Achieving a 50% Improvement in BASDAI Response from Baseline (BASDAI 50) at Weeks 2, 4, 8 and 12

Secondary: Change from Baseline in Bath Ankylosing Spondylitis Functional Index (BASFI) at Weeks 2, 4, 8 and 12

Secondary: Change from Baseline in Bath Ankylosing Spondylitis Functional Index (BASFI) at Weeks 2, 4, 8 and 12

Secondary: Change from Baseline in Bath Ankylosing Spondylitis Metrology Index (BASMI) at Weeks 2, 4, 8 and 12

Secondary: Change from Baseline in Bath Ankylosing Spondylitis Metrology Index (BASMI) at Weeks 2, 4, 8 and 12

Secondary: Change from Baseline in Maastricht Ankylosing Spondylitis Enthesitis Score (MASES) at Weeks 4, 8 and 12

Secondary: Change from Baseline in Maastricht Ankylosing Spondylitis Enthesitis Score (MASES) at Weeks 4, 8 and 12

Secondary: Extra-Articular Involvement from Specific Ankylosing Spondylitis Medical History

Secondary: Extra-Articular Involvement from Specific Ankylosing Spondylitis Medical History

Secondary: Change from Baseline of Total Swollen Joint Count at Weeks 2, 4, 8, and 12

Secondary: Change from Baseline of Total Swollen Joint Count at Weeks 2, 4, 8, and 12

Secondary: Change from Baseline of Mean Spinal Mobility (Chest Expansion) at Week 2, 4, 8 and 12

Secondary: Change from Baseline of Mean Spinal Mobility (Chest Expansion) at Week 2, 4, 8 and 12

Secondary: Change from Baseline to Week 12 in Short-Form-36 Health Survey (SF-36) Physical and Mental Health Scores at Week 12

Secondary: Change from Baseline to Week 12 in Short-Form-36 Health Survey (SF-36) Physical and Mental Health Scores at Week 12

Secondary: Change from Baseline in EuroQol EQ-5D Health State Profile (EQ-5D) Utility Score at Week 12

Secondary: Change from Baseline in EuroQol EQ-5D Health State Profile (EQ-5D) Utility Score at Week 12

Secondary: Change from Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Score at Weeks 2, 4, 8 and 12

Secondary: Change from Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Score at Weeks 2, 4, 8 and 12

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Dose-Ranging Study of the Efficacy and Safety of Tofacitinib in Subjects with Active Ankylosing Spondylitis (AS)