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Clinical Trial Results:
An Exploratory Phase 2, Randomized, Double-blind, Multicenter Study To Assess The Effects Of Tofacitinib (CP-690,550) ON Magnetic Resonance Imaging Endpoints, In Methotrexate Naïve Subjects With Early Active Rheumatoid Arthritis

Summary
EudraCT number	2010-020890-18
Trial protocol	CZ HU
Global end of trial date	05 Nov 2013

Results information
Results version number	v1(current)
This version publication date	23 May 2016
First version publication date	25 Jul 2015
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

A3921068

ISRCTN number

US NCT number

NCT01164579

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

Scientific contact

Pfizer Clinical Trials.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

03 Nov 2014

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

05 Nov 2013

Was the trial ended prematurely?

Main objective of the trial

To estimate the effect of CP-690,550 administered as a Disease-Modifying Antirheumatic Drug (DMARD) monotherapy or in combination with Methotrexate (MTX) vs MTX alone on changes from baseline in wrist and metacarpophalangeal joints (MCP) bone marrow edema at Month 6 and wrist and MCP synovitis at Month 3, as assessed by utilizing the Outcome Measures in Rheumatology Clinical Trials (OMERACT) Rheumatoid Arthritis Magnetic Resonance Imaging Score (RAMRIS) in subjects with early Rheumatoid Arthritis (RA).

Protection of trial subjects

The study was in compliance with the ethical principles derived from the Declaration of Helsinki and in compliance with all International Conference on Harmonization (ICH) Good Clinical Practice (GCP) Guidelines. All the local regulatory requirements pertinent to safety of trial subjects were followed.

Background therapy

Evidence for comparator

Actual start date of recruitment

25 Oct 2010

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Poland: 18

Country: Number of subjects enrolled

Chile: 11

Country: Number of subjects enrolled

Croatia: 1

Country: Number of subjects enrolled

Czech Republic: 15

Country: Number of subjects enrolled

Hungary: 8

Country: Number of subjects enrolled

Argentina: 5

Country: Number of subjects enrolled

Mexico: 35

Country: Number of subjects enrolled

Puerto Rico: 3

Country: Number of subjects enrolled

United States: 13

Worldwide total number of subjects

109

EEA total number of subjects

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

Screening details

Study was initiated on 25 October 2010 and completed on 05 November 2013. Subjects were enrolled from 9 countries (Poland, Chile, Croatia, Czech Republic, Hungary, Argentina, Mexico, Puerto Rico and United States).

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator

Are arms mutually exclusive

Yes

Tofacitinib (CP- 690,550) Plus Methotrexate (MTX)

Arm description

Subjects received CP-690,550 tablets, twice daily (BID), and MTX capsules, for a maximum of 12 months. Subjects also received folate supplementation according to local MTX label guidelines and standard of care.

Arm type

Experimental

Investigational medicinal product name

Tofacitinib

Investigational medicinal product code

CP-690,550

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

10 milligram (mg) tablets, orally (PO), twice daily (BID) for a maximum of 12 months.

Investigational medicinal product name

Methotrexate

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

10 mg per week (mg/week) to 20 mg/week, PO for a maximum of 12 months. MTX dose was titrated as follows: 10 mg once weekly for 4 weeks; if well tolerated, then at Month 1 titrated up to 15 mg once weekly for 4 weeks; if well tolerated, then at Month 2 titrated up to 20 mg once weekly for the duration of the study. A single dose reduction of MTX 5 mg was allowed because of lack of tolerance, as long as the subject remained on a dose of at least MTX 10 mg weekly.

Tofacitinib (CP- 690,550)

Arm description

Subjects received CP-690,550 tablets, BID and matching placebo MTX capsules for a maximum of 12 months. Subjects also received folate supplementation according to local MTX label guidelines and standard of care.

Arm type

Experimental

Investigational medicinal product name

Tofacitinib

Investigational medicinal product code

CP-690,550

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

10 mg tablets, PO, BID for a maximum of 12 months.

Investigational medicinal product name

Placebo Methotrexate

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Matching placebo MTX capsules, PO, once weekly for a maximum of 12 months. To maintain the blind, matching placebo MTX was titrated as follows: 4 capsules once weekly for 4 weeks; if well tolerated, at Month 1 titrated up to 6 capsules once weekly for 4 weeks; if well tolerated, then at Month 2 titrated up to 8 capsules once weekly for the duration of the study. A single dose reduction of MTX placebo to 2 capsules was allowed because of lack of tolerance, as long as the subject remained on a dose of at least 4 MTX placebo capsules weekly.

Methotrexate

Arm description

Subjects received MTX capsules and matching placebo CP-690,550 tablets. Subjects also received folate supplementation according to local MTX label guidelines and standard of care.

Arm type

Active comparator

Investigational medicinal product name

Methotrexate

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

10 mg/week to 20 mg/week, PO. MTX dose was titrated as follows: 10 mg once weekly for 4 weeks; if well tolerated, then at Month 1 titrated up to 15 mg once weekly for 4 weeks; if well tolerated, then at Month 2 titrated up to 20 mg once weekly for the duration of the study. A single dose reduction of MTX 5 mg was allowed because of lack of tolerance, as long as the subject remained on a dose of at least MTX 10 mg weekly.

Investigational medicinal product name

Placebo Tofacitinib

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Matching placebo CP-690,550 tablets, PO, BID.

Number of subjects in period 1	Tofacitinib (CP- 690,550) Plus Methotrexate (MTX)	Tofacitinib (CP- 690,550)	Methotrexate
Started	36	36	37
Completed	28	27	21
Not completed	8	9	16
Consent withdrawn by subject	2	5	3
Adverse Event	4	2	5
Protocol Violation	-	1	2
Lost to follow-up	1	1	-
Reason not Specified	1	-	-
Lack of efficacy	-	-	6

Baseline characteristics

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Reporting group title

Tofacitinib (CP- 690,550) Plus Methotrexate (MTX)

Reporting group description

Reporting group title

Tofacitinib (CP- 690,550)

Reporting group description

Reporting group title

Methotrexate

Reporting group description

Subjects received MTX capsules and matching placebo CP-690,550 tablets. Subjects also received folate supplementation according to local MTX label guidelines and standard of care.

Reporting group values	Tofacitinib (CP- 690,550) Plus Methotrexate (MTX)	Tofacitinib (CP- 690,550)	Methotrexate	Total
Number of subjects	36	36	37	109
Age categorical
Units: Subjects
Age continuous
Units: years
arithmetic mean (standard deviation)	47.8 ± 12.3	50.8 ± 12.8	47.8 ± 11.6	-
Gender categorical
Units: Subjects
Female	31	30	29	90
Male	5	6	8	19

End points

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Reporting group title

Tofacitinib (CP- 690,550) Plus Methotrexate (MTX)

Reporting group description

Reporting group title

Tofacitinib (CP- 690,550)

Reporting group description

Reporting group title

Methotrexate

Reporting group description

Subjects received MTX capsules and matching placebo CP-690,550 tablets. Subjects also received folate supplementation according to local MTX label guidelines and standard of care.

Primary: Change From Baseline to Month 3 in Outcome Measures in Rheumatoid Arthritis Clinical Trials (OMERACT) Rheumatoid Arthritis Magnetic Resonance Imaging Score (RAMRIS) Wrist and Metacarpophalangeal (MCP) Synovitis

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End point title

Change From Baseline to Month 3 in Outcome Measures in Rheumatoid Arthritis Clinical Trials (OMERACT) Rheumatoid Arthritis Magnetic Resonance Imaging Score (RAMRIS) Wrist and Metacarpophalangeal (MCP) Synovitis

End point description

Synovitis: an area in synovial compartment that shows above normal postgadolinium enhancement of thickness greater than width of normal synovium. T1-weighted images were acquired before,after administration of intravenous (IV) contrast agent containing gadolinium. IV contrast was required to demonstrate enhancing synovitis. Synovitis was scored 0 to 3 in 3 wrist regions in each of the first through fifth MCP joints. Score of 0 is normal,with no enhancement or enhancement up to thickness of normal synovium,while scores of 1 to 3(mild, moderate, severe) refer to increments of one-third of presumed maximum volume of enhancing tissue in synovial compartment. Total synovitis score ranges from a minimum of 0 to a maximum of 24. A negative value in synovitis change from baseline score indicates improvement. Evaluable Set: all randomized subjects who received at least 1 dose of randomized investigational drug and for whom a variable is nonmissing at both baseline and the specified time point.

End point type

Primary

End point timeframe

Month 3

End point values	Tofacitinib (CP- 690,550) Plus Methotrexate (MTX)	Tofacitinib (CP- 690,550)	Methotrexate
Number of subjects analysed	30	32	31
Units: score on a scale
least squares mean (standard error)	-0.8 ± 0.41	-0.69 ± 0.4	-0.17 ± 0.4

Tofacitinib Plus MTX vs MTX

Comparison groups

Tofacitinib (CP- 690,550) Plus Methotrexate (MTX) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.2696 ^[1]

Method

mixed model repeated measures analysis

Parameter type

Difference in least squares (LS) Mean

Point estimate

-0.63

Confidence interval

level

90%

sides

2-sided

lower limit

-1.58

upper limit

0.31

Variability estimate

Standard error of the mean

Dispersion value

0.57

Notes
[1] - 2-sided p-value; alpha equals (=) 0.10.

Tofacitinib vs MTX

Comparison groups

Methotrexate v Tofacitinib (CP- 690,550)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.3561 ^[2]

Method

mixed model repeated measures analysis

Parameter type

Difference in LS Mean

Point estimate

-0.52

Confidence interval

level

90%

sides

2-sided

lower limit

-1.46

upper limit

0.41

Variability estimate

Standard error of the mean

Dispersion value

0.57

Notes
[2] - 2-sided p-value; alpha=0.10.

Primary: Change From Baseline to Month 6 in OMERACT RAMRIS Wrist and MCP Bone Marrow Edema

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End point title

Change From Baseline to Month 6 in OMERACT RAMRIS Wrist and MCP Bone Marrow Edema

End point description

Bone edema was assessed at 25 anatomic locations: 15 in 1 wrist and 10 in attached hand. Bone edema was defined as a lesion within the trabecular bone, with ill-defined margins and signal characteristics consistent with increased water content. Each bone was scored separately; the scale was 0 to 3 based on the proportion of bone with edema, as follows 0: no edema; 1: 1-33 per cent (%) of bone edematous; 2: 34-66% of bone edematous; 3: 67-100%. OMERACT RAMRIS total bone edema score for hands/wrists was sum of the individual scores for each location. Thus the maximum score per hand/wrist was 75 (range 0-75). Increasing score=greater severity. Evaluable Set.

End point type

Primary

End point timeframe

Month 6

End point values	Tofacitinib (CP- 690,550) Plus Methotrexate (MTX)	Tofacitinib (CP- 690,550)	Methotrexate
Number of subjects analysed	33	29	28
Units: score on a scale
least squares mean (standard error)	-1.26 ± 0.41	-1.45 ± 0.42	0.29 ± 0.42

Tofacitinib Plus MTX vs MTX

Comparison groups

Methotrexate v Tofacitinib (CP- 690,550) Plus Methotrexate (MTX)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.0089 ^[3]

Method

mixed model repeated measures analysis

Parameter type

Difference in LS Means

Point estimate

-1.55

Confidence interval

level

90%

sides

2-sided

lower limit

-2.52

upper limit

-0.58

Variability estimate

Standard error of the mean

Dispersion value

0.59

Notes
[3] - 2-sided p-value; alpha= 0.10.

Tofacitinib vs MTX

Comparison groups

Tofacitinib (CP- 690,550) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.0038 ^[4]

Method

mixed model repeated measures analysis

Parameter type

Difference in LS Means

Point estimate

-1.74

Confidence interval

level

90%

sides

2-sided

lower limit

-2.72

upper limit

-0.76

Variability estimate

Standard error of the mean

Dispersion value

0.59

Notes
[4] - 2-sided p-value; alpha= 0.10.

Secondary: Change From Baseline to Months 1, 6, and 12 in OMERACT RAMRIS Wrist and MCP Synovitis

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End point title

Change From Baseline to Months 1, 6, and 12 in OMERACT RAMRIS Wrist and MCP Synovitis

End point description

Synovitis is defined as an area in the synovial compartment that shows above normal postgadolinium enhancement of a thickness greater than the width of the normal synovium. T1-weighted images were acquired before and after the administration of intravenous contrast agent containing gadolinium. Intravenous contrast was required to demonstrate enhancing synovitis. Synovitis was scored 0 to 3 in 3 wrist regions and in each of the first through fifth MCP joints. A score of 0 is normal, with no enhancement or enhancement up to the thickness of normal synovium, while scores of 1 to 3 (mild, moderate, severe) refer to increments of one-third of the presumed maximum volume of enhancing tissue in the synovial compartment. Total synovitis score ranges from a minimum of 0 to a maximum of 24. A negative value in synovitis change from Baseline score indicates an improvement. Evaluable Set.

End point type

Secondary

End point timeframe

Month 1, 6, 12

End point values	Tofacitinib (CP- 690,550) Plus Methotrexate (MTX)	Tofacitinib (CP- 690,550)	Methotrexate
Number of subjects analysed	33	31	35
Units: score on a scale
least squares mean (standard error)
Month 1 (n=28,31,35)	-0.42 ± 0.42	-0.34 ± 0.4	-0.17 ± 0.38
Month 6 (n=33,29,28)	-1.22 ± 0.4	-1.29 ± 0.41	-0.28 ± 0.42
Month 12 (n=29,26,21)	-2.26 ± 0.41	-1.16 ± 0.43	-0.66 ± 0.46

Tofacitinib Plus MTX vs MTX at Month 1

Comparison groups

Tofacitinib (CP- 690,550) Plus Methotrexate (MTX) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.6576 ^[5]

Method

mixed model repeated measures analysis

Parameter type

Difference in LS Means

Point estimate

-0.25

Confidence interval

level

90%

sides

2-sided

lower limit

-1.19

upper limit

0.69

Variability estimate

Standard error of the mean

Dispersion value

0.57

Notes
[5] - 2-sided p-value; alpha=0.10.

Tofacitinib vs MTX at Month 1

Comparison groups

Methotrexate v Tofacitinib (CP- 690,550)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.7565 ^[6]

Method

mixed model repeated measures analysis

Parameter type

Difference in LS Means

Point estimate

-0.17

Confidence interval

level

90%

sides

2-sided

lower limit

-1.09

upper limit

0.74

Variability estimate

Standard error of the mean

Dispersion value

0.55

Notes
[6] - 2-sided p-value; alpha=0.10.

Tofacitinib Plus MTX vs MTX at Month 6

Comparison groups

Tofacitinib (CP- 690,550) Plus Methotrexate (MTX) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.1038 ^[7]

Method

mixed model repeated measures analysis

Parameter type

Difference in LS Means

Point estimate

-0.94

Confidence interval

level

90%

sides

2-sided

lower limit

-1.89

upper limit

0.01

Variability estimate

Standard error of the mean

Dispersion value

0.58

Notes
[7] - 2-sided p-value; alpha=0.10.

Tofacitinib vs MTX at Month 6

Comparison groups

Tofacitinib (CP- 690,550) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.0868 ^[8]

Method

mixed model repeated measures analysis

Parameter type

Difference in LS Means

Point estimate

-1.01

Confidence interval

level

90%

sides

2-sided

lower limit

-1.98

upper limit

-0.04

Variability estimate

Standard error of the mean

Dispersion value

0.59

Notes
[8] - 2-sided p-value; alpha=0.10.

Tofacitinib Plus MTX vs MTX at Month 12

Comparison groups

Tofacitinib (CP- 690,550) Plus Methotrexate (MTX) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.0103 ^[9]

Method

mixed model repeated measures analysis

Parameter type

Difference in LS Means

Point estimate

-1.6

Confidence interval

level

90%

sides

2-sided

lower limit

-2.62

upper limit

-0.58

Variability estimate

Standard error of the mean

Dispersion value

0.62

Notes
[9] - 2-sided p-value; alpha=0.10.

Tofacitinib vs MTX at Month 12

Comparison groups

Tofacitinib (CP- 690,550) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.435 ^[10]

Method

mixed model repeated measures analysis

Parameter type

Difference in LS Means

Point estimate

-0.49

Confidence interval

level

90%

sides

2-sided

lower limit

-1.53

upper limit

0.55

Variability estimate

Standard error of the mean

Dispersion value

0.63

Notes
[10] - 2-sided p-value; alpha=0.10.

Secondary: Change From Baseline to Months 1, 3, and 12 in OMERACT RAMRIS Bone Marrow Edema in Wrist and MCP

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End point title

Change From Baseline to Months 1, 3, and 12 in OMERACT RAMRIS Bone Marrow Edema in Wrist and MCP

End point description

Bone edema was assessed at 25 anatomic locations: 15 in 1 wrist and 10 in attached hand. Bone edema was defined as a lesion within the trabecular bone, with ill-defined margins and signal characteristics consistent with increased water content. Each bone was scored separately; the scale was 0 to 3 based on the proportion of bone with edema, as follows 0: no edema; 1: 1-33% of bone edematous; 2: 34-66% of bone edematous; 3: 67-100%. OMERACT RAMRIS total bone edema score for hands/wrists was sum of the individual scores for each location. Thus the maximum score per hand/wrist was 75 (range 0-75). Increasing score=greater severity. Evaluable Set; n=number of subjects assessed for the specified parameter at a given visit.

End point type

Secondary

End point timeframe

Month 1, 3, 12

End point values	Tofacitinib (CP- 690,550) Plus Methotrexate (MTX)	Tofacitinib (CP- 690,550)	Methotrexate
Number of subjects analysed	30	32	35
Units: score on a scale
least squares mean (standard error)
Month 1 (n=28,31,35)	-0.29 ± 0.43	0.19 ± 0.41	0.11 ± 0.39
Month 3 (n=30,32,31)	-0.77 ± 0.42	-0.86 ± 0.41	0.47 ± 0.41
Month 12 (n=29,26,21)	-1.52 ± 0.42	-1.7 ± 0.43	0.59 ± 0.46

Tofacitinib Plus MTX vs MTX at Month 1

Comparison groups

Tofacitinib (CP- 690,550) Plus Methotrexate (MTX) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.489 ^[11]

Method

mixed model repeated measures analysis

Parameter type

Difference in LS Means

Point estimate

-0.4

Confidence interval

level

90%

sides

2-sided

lower limit

-1.36

upper limit

0.56

Variability estimate

Standard error of the mean

Dispersion value

0.58

Notes
[11] - 2-sided p-value; alpha=0.10.

Tofacitinib vs MTX at Month 1

Comparison groups

Tofacitinib (CP- 690,550) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.8817 ^[12]

Method

mixed model repeated measures analysis

Parameter type

Difference in LS Means

Point estimate

0.08

Confidence interval

level

90%

sides

2-sided

lower limit

-0.85

upper limit

1.02

Variability estimate

Standard error of the mean

Dispersion value

0.57

Notes
[12] - 2-sided p-value; alpha=0.10.

Tofacitinib Plus MTX vs MTX at Month 3

Comparison groups

Tofacitinib (CP- 690,550) Plus Methotrexate (MTX) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.0351 ^[13]

Method

mixed model repeated measures analysis

Parameter type

Difference in LS Means

Point estimate

-1.24

Confidence interval

level

90%

sides

2-sided

lower limit

-2.21

upper limit

-0.27

Variability estimate

Standard error of the mean

Dispersion value

0.59

Notes
[13] - 2-sided p-value; alpha=0.10.

Tofacitinib vs MTX at Month 3

Comparison groups

Tofacitinib (CP- 690,550) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.0231 ^[14]

Method

mixed model repeated measures analysis

Parameter type

Difference in LS Means

Point estimate

-1.32

Confidence interval

level

90%

sides

2-sided

lower limit

-2.28

upper limit

-0.37

Variability estimate

Standard error of the mean

Dispersion value

0.58

Notes
[14] - 2-sided p-value; alpha=0.10.

Tofacitinib Plus MTX vs MTX at Month 12

Comparison groups

Tofacitinib (CP- 690,550) Plus Methotrexate (MTX) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.0008 ^[15]

Method

mixed model repeated measures analysis

Parameter type

Difference in LS Means

Point estimate

-2.1

Confidence interval

level

90%

sides

2-sided

lower limit

-3.13

upper limit

-1.08

Variability estimate

Standard error of the mean

Dispersion value

0.62

Notes
[15] - 2-sided p-value; alpha=0.10.

Tofacitinib vs MTX at Month 12

Comparison groups

Tofacitinib (CP- 690,550) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.0003 ^[16]

Method

mixed model repeated measures analysis

Parameter type

Difference in LS Means

Point estimate

-2.29

Confidence interval

level

90%

sides

2-sided

lower limit

-3.32

upper limit

-1.25

Variability estimate

Standard error of the mean

Dispersion value

0.63

Notes
[16] - 2-sided p-value; alpha=0.10.

Secondary: Change From Baseline to Months 1, 3, 6, and 12 in OMERACT RAMRIS Wrist and MCP Erosions

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End point title

Change From Baseline to Months 1, 3, 6, and 12 in OMERACT RAMRIS Wrist and MCP Erosions

End point description

Bone erosion assessed at 25 anatomic locations: 15 in 1 wrist and 10 in attached hand. Each site was scored in 1.0 increments from 0 (no damage) to 10 (severe damage), indicating erosion (each unit=10% bone loss) of original articular bone. OMERACT RAMRIS total erosion score for hands/wrists was sum of the individual scores for each location. Thus the maximum score per hand/wrist is 250 (range 0-250). Increasing score=greater severity. Evaluable Set.

End point type

Secondary

End point timeframe

Month 1, 3, 6, 12

End point values	Tofacitinib (CP- 690,550) Plus Methotrexate (MTX)	Tofacitinib (CP- 690,550)	Methotrexate
Number of subjects analysed	33	32	35
Units: score on a scale
least squares mean (standard error)
Month 1 (n=28,31,35)	-0.12 ± 0.25	0.27 ± 0.25	0.27 ± 0.24
Month 3 (n=30,32,31)	-0.12 ± 0.25	0.36 ± 0.24	0.44 ± 0.25
Month 6 (n=33,29,28)	-0.06 ± 0.25	-0.02 ± 0.25	0.65 ± 0.25
Month 12 (n=29,26,21)	-0.11 ± 0.25	-0.08 ± 0.25	1.18 ± 0.26

Tofacitinib Plus MTX vs MTX at Month 1

Comparison groups

Tofacitinib (CP- 690,550) Plus Methotrexate (MTX) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.2689 ^[17]

Method

mixed model repeated measures analysis

Parameter type

Difference in LS Means

Point estimate

-0.39

Confidence interval

level

90%

sides

2-sided

lower limit

-0.96

upper limit

0.19

Variability estimate

Standard error of the mean

Dispersion value

0.35

Notes
[17] - 2-sided p-value; alpha=0.10 .

Tofacitinib vs MTX at Month 1

Comparison groups

Methotrexate v Tofacitinib (CP- 690,550)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.9935 ^[18]

Method

mixed model repeated measures analysis

Parameter type

Difference in LS Means

Point estimate

Confidence interval

level

90%

sides

2-sided

lower limit

-0.58

upper limit

0.57

Variability estimate

Standard error of the mean

Dispersion value

0.35

Notes
[18] - 2-sided p-value; alpha=0.10.

Tofacitinib Plus MTX vs MTX at Month 3

Comparison groups

Tofacitinib (CP- 690,550) Plus Methotrexate (MTX) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.1086 ^[19]

Method

mixed model repeated measures analysis

Parameter type

Difference in LS Means

Point estimate

-0.57

Confidence interval

level

90%

sides

2-sided

lower limit

-1.15

upper limit

0.01

Variability estimate

Standard error of the mean

Dispersion value

0.35

Notes
[19] - 2-sided p-value; alpha=0.10.

Tofacitinib vs MTX at Month 3

Comparison groups

Tofacitinib (CP- 690,550) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.8092 ^[20]

Method

mixed model repeated measures analysis

Parameter type

Difference in LS Means

Point estimate

-0.08

Confidence interval

level

90%

sides

2-sided

lower limit

-0.66

upper limit

0.49

Variability estimate

Standard error of the mean

Dispersion value

0.35

Notes
[20] - 2-sided p-value; alpha=0.10.

Tofacitinib Plus MTX vs MTX at Month 6

Comparison groups

Tofacitinib (CP- 690,550) Plus Methotrexate (MTX) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.0463 ^[21]

Method

mixed model repeated measures analysis

Parameter type

Difference in LS Means

Point estimate

-0.71

Confidence interval

level

90%

sides

2-sided

lower limit

-1.29

upper limit

-0.12

Variability estimate

Standard error of the mean

Dispersion value

0.35

Notes
[21] - 2-sided p-value; alpha=0.10.

Tofacitinib vs MTX at Month 6

Comparison groups

Tofacitinib (CP- 690,550) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.0624 ^[22]

Method

mixed model repeated measures analysis

Parameter type

Difference in LS Means

Point estimate

-0.67

Confidence interval

level

90%

sides

2-sided

lower limit

-1.25

upper limit

-0.08

Variability estimate

Standard error of the mean

Dispersion value

0.35

Notes
[22] - 2-sided p-value; alpha=0.10.

Tofacitinib Plus MTX vs MTX at Month 12

Comparison groups

Tofacitinib (CP- 690,550) Plus Methotrexate (MTX) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.0005 ^[23]

Method

mixed model repeated measures analysis

Parameter type

Difference in LS Means

Point estimate

-1.29

Confidence interval

level

90%

sides

2-sided

lower limit

-1.9

upper limit

-0.69

Variability estimate

Standard error of the mean

Dispersion value

0.37

Notes
[23] - 2-sided p-value; alpha=0.10.

Tofacitinib vs MTX at Month 12

Comparison groups

Tofacitinib (CP- 690,550) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.0008 ^[24]

Method

mixed model repeated measures analysis

Parameter type

Difference in LS Means

Point estimate

-1.26

Confidence interval

level

90%

sides

2-sided

lower limit

-1.87

upper limit

-0.65

Variability estimate

Standard error of the mean

Dispersion value

0.37

Notes
[24] - 2-sided p-value; alpha=0.10.

Secondary: Modified Total Sharp Score (mTSS) at Months 6 and 12

Top of page

End point title

Modified Total Sharp Score (mTSS) at Months 6 and 12

End point description

Modified TSS is a measure of change in joint health. TSS is defined as joint space narrowing score (range 0 [no narrowing] to 168 [high narrowing]) plus (+) erosion score (range is from 0 [no erosion] to 280 [high erosion]). The modified TSS range is from 0 (no damage) to 448 (bad joint status). Increase from baseline represents disease progression and / or joint worsening; no change represents halting of disease progression; a decrease represents improvement. Evaluable Set; n=number of subjects assessed for the specified parameter at a given visit.

End point type

Secondary

End point timeframe

Month 6, 12.

End point values	Tofacitinib (CP- 690,550) Plus Methotrexate (MTX)	Tofacitinib (CP- 690,550)	Methotrexate
Number of subjects analysed	34	36	37
Units: score on a scale
least squares mean (standard error)
Month 6 (n=29,27,28)	11.28 ± 0.5	10.7 ± 0.51	11.77 ± 0.52
Month 12 (n=26,25,22)	11.7 ± 0.51	10.69 ± 0.52	12.21 ± 0.54

Tofacitinib Plus MTX vs MTX at Month 6

Comparison groups

Tofacitinib (CP- 690,550) Plus Methotrexate (MTX) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.5019 ^[25]

Method

mixed model repeated measures analysis

Parameter type

Difference in LS Means

Point estimate

-0.48

Confidence interval

level

90%

sides

2-sided

lower limit

-1.68

upper limit

0.71

Variability estimate

Standard error of the mean

Dispersion value

0.72

Notes
[25] - 2-sided p-value; alpha=0.10.

Tofacitinib vs MTX at Month 6

Comparison groups

Methotrexate v Tofacitinib (CP- 690,550)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.1462 ^[26]

Method

mixed model repeated measures analysis

Parameter type

Difference in LS Means

Point estimate

-1.07

Confidence interval

level

90%

sides

2-sided

lower limit

-2.28

upper limit

0.14

Variability estimate

Standard error of the mean

Dispersion value

0.73

Notes
[26] - 2-sided p-value; alpha=0.10.

Tofacitinib Plus MTX vs MTX at Month 12

Comparison groups

Tofacitinib (CP- 690,550) Plus Methotrexate (MTX) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.49 ^[27]

Method

mixed model repeated measures analysis

Parameter type

Difference in LS Means

Point estimate

-0.51

Confidence interval

level

90%

sides

2-sided

lower limit

-1.74

upper limit

0.72

Variability estimate

Standard error of the mean

Dispersion value

0.74

Notes
[27] - 2-sided p-value; alpha=0.10.

Tofacitinib vs MTX at Month 12

Comparison groups

Tofacitinib (CP- 690,550) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.0459

Method

mixed model repeated measures analysis

Parameter type

Difference in LS Means

Point estimate

-1.51

Confidence interval

level

90%

sides

2-sided

lower limit

-2.76

upper limit

-0.27

Variability estimate

Standard error of the mean

Dispersion value

0.75

Secondary: Change From Baseline to Months 6 and 12 in mTSS

Top of page

End point title

Change From Baseline to Months 6 and 12 in mTSS

End point description

Modified TSS is a measure of change in joint health. TSS is defined as joint space narrowing score (range 0 [no narrowing] to 168 [high narrowing]) + erosion score (range is from 0 [no erosion] to 280 [high erosion]). The modified TSS range is from 0 (no damage) to 448 (bad joint status). Increase from baseline represents disease progression and / or joint worsening; no change represents halting of disease progression; a decrease represents improvement. Evaluable Set; n=number of subjects assessed for the specified parameter at a given visit.

End point type

Secondary

End point timeframe

Month 6, 12

End point values	Tofacitinib (CP- 690,550) Plus Methotrexate (MTX)	Tofacitinib (CP- 690,550)	Methotrexate
Number of subjects analysed	29	27	28
Units: scores on a scale
least squares mean (standard error)
Month 6 (n=29,27,28)	0.44 ± 0.5	-0.14 ± 0.51	0.93 ± 0.52
Month 12 (n=26,25,22)	0.85 ± 0.51	-0.15 ± 0.52	1.36 ± 0.54

Tofacitinib Plus MTX vs MTX at Month 6

Comparison groups

Tofacitinib (CP- 690,550) Plus Methotrexate (MTX) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.5019 ^[28]

Method

mixed model repeated measures analysis

Parameter type

Difference in LS Means

Point estimate

-0.48

Confidence interval

level

90%

sides

2-sided

lower limit

-1.68

upper limit

0.71

Variability estimate

Standard error of the mean

Dispersion value

0.72

Notes
[28] - 2-sided p-value; alpha=0.10.

Tofacitinib vs MTX at Month 6

Comparison groups

Tofacitinib (CP- 690,550) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.1462 ^[29]

Method

mixed model repeated measures analysis

Parameter type

Difference in LS Means

Point estimate

-1.07

Confidence interval

level

90%

sides

2-sided

lower limit

-2.28

upper limit

0.14

Variability estimate

Standard error of the mean

Dispersion value

0.73

Notes
[29] - 2-sided p-value; alpha=0.10.

Tofacitinib Plus MTX vs MTX at Month 12

Comparison groups

Tofacitinib (CP- 690,550) Plus Methotrexate (MTX) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.49 ^[30]

Method

mixed model repeated measures analysis

Parameter type

Difference in LS Means

Point estimate

-0.51

Confidence interval

level

90%

sides

2-sided

lower limit

-1.74

upper limit

0.72

Variability estimate

Standard error of the mean

Dispersion value

0.74

Notes
[30] - 2-sided p-value; alpha=0.10.

Tofacitinib vs MTX at Month 12

Comparison groups

Tofacitinib (CP- 690,550) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.0459 ^[31]

Method

mixed model repeated measures analysis

Parameter type

Difference in LS Means

Point estimate

-1.51

Confidence interval

level

90%

sides

2-sided

lower limit

-2.76

upper limit

-0.27

Variability estimate

Standard error of the mean

Dispersion value

0.75

Notes
[31] - 2-sided p-value; alpha=0.10.

Secondary: Joint Space Narrowing (JSN) Scores at Months 6 and 12

Top of page

End point title

Joint Space Narrowing (JSN) Scores at Months 6 and 12

End point description

JSN score (a component of the modified TSS) is a measure of change in joint health. JSN score range is 0 (no narrowing) to 168 (high narrowing). Increase from baseline represents disease progression and / or joint worsening; no change represents halting of disease progression; a decrease represents improvement. Evaluable Set; n=number of subjects assessed for the specified parameter at a given visit.

End point type

Secondary

End point timeframe

Month 6, 12.

End point values	Tofacitinib (CP- 690,550) Plus Methotrexate (MTX)	Tofacitinib (CP- 690,550)	Methotrexate
Number of subjects analysed	29	27	28
Units: score on a scale
least squares mean (standard error)
Month 6 (n=29,27,28)	5.45 ± 0.34	5.11 ± 0.35	5.52 ± 0.36
Month 12 (n=26,25,22)	5.59 ± 0.35	5.05 ± 0.36	5.88 ± 0.37

Tofacitinib Plus MTX vs MTX at Month 6

Comparison groups

Tofacitinib (CP- 690,550) Plus Methotrexate (MTX) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.8959 ^[32]

Method

mixed model repeated measures analysis

Parameter type

Difference in LS Means

Point estimate

-0.07

Confidence interval

level

90%

sides

2-sided

lower limit

-0.89

upper limit

0.76

Variability estimate

Standard error of the mean

Dispersion value

0.5

Notes
[32] - 2-sided p-value; alpha=0.10.

Tofacitinib vs MTX at Month 6

Comparison groups

Tofacitinib (CP- 690,550) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.4193 ^[33]

Method

mixed model repeated measures analysis

Parameter type

Difference in LS Means

Point estimate

-0.41

Confidence interval

level

90%

sides

2-sided

lower limit

-1.25

upper limit

0.43

Variability estimate

Standard error of the mean

Dispersion value

0.5

Notes
[33] - 2-sided p-value; alpha=0.10.

Tofacitinib Plus MTX vs MTX at Month 12

Comparison groups

Tofacitinib (CP- 690,550) Plus Methotrexate (MTX) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.5764 ^[34]

Method

mixed model repeated measures analysis

Parameter type

Difference in LS Means

Point estimate

-0.29

Confidence interval

level

90%

sides

2-sided

lower limit

-1.13

upper limit

0.56

Variability estimate

Standard error of the mean

Dispersion value

0.51

Notes
[34] - 2-sided p-value; alpha=0.10.

Tofacitinib vs MTX at Month 12

Comparison groups

Tofacitinib (CP- 690,550) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.1101 ^[35]

Method

mixed model repeated measures analysis

Parameter type

Difference in LS Means

Point estimate

-0.83

Confidence interval

level

90%

sides

2-sided

lower limit

-1.69

upper limit

0.02

Variability estimate

Standard error of the mean

Dispersion value

0.52

Notes
[35] - 2-sided p-value; alpha=0.10.

Secondary: Change From Baseline to Months 6 and 12 in JSN Scores

Top of page

End point title

Change From Baseline to Months 6 and 12 in JSN Scores

End point description

End point type

Secondary

End point timeframe

Months 6 and 12

End point values	Tofacitinib (CP- 690,550) Plus Methotrexate (MTX)	Tofacitinib (CP- 690,550)	Methotrexate
Number of subjects analysed	29	27	28
Units: scores on a scale
least squares mean (standard error)
Month 6 (n=29,27,28)	0.29 ± 0.34	-0.06 ± 0.35	0.35 ± 0.36
Month 12 (n=26,25,22)	0.43 ± 0.35	-0.12 ± 0.36	0.71 ± 0.37

Tofacitinib Plus MTX vs MTX at Month 6

Comparison groups

Tofacitinib (CP- 690,550) Plus Methotrexate (MTX) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.8959 ^[36]

Method

mixed model repeated measures analysis

Parameter type

Difference in LS Means

Point estimate

-0.07

Confidence interval

level

90%

sides

2-sided

lower limit

-0.89

upper limit

0.76

Variability estimate

Standard error of the mean

Dispersion value

0.5

Notes
[36] - 2-sided p-value; alpha=0.10.

Tofacitinib vs MTX at Month 6

Comparison groups

Tofacitinib (CP- 690,550) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.4193 ^[37]

Method

mixed model repeated measures analysis

Parameter type

Difference in LS Means

Point estimate

-0.41

Confidence interval

level

90%

sides

2-sided

lower limit

-1.25

upper limit

0.43

Variability estimate

Standard error of the mean

Dispersion value

0.5

Notes
[37] - 2-sided p-value; alpha=0.10.

Tofacitinib Plus MTX vs MTX at Month 12

Comparison groups

Tofacitinib (CP- 690,550) Plus Methotrexate (MTX) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.5764 ^[38]

Method

mixed model repeated measures analysis

Parameter type

Difference in LS Means

Point estimate

-0.29

Confidence interval

level

90%

sides

2-sided

lower limit

-1.13

upper limit

0.56

Variability estimate

Standard error of the mean

Dispersion value

0.51

Notes
[38] - 2-sided p-value; alpha=0.10.

Tofacitinib vs MTX at Month 12

Comparison groups

Tofacitinib (CP- 690,550) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.1101 ^[39]

Method

mixed model repeated measures analysis

Parameter type

Difference in LS Means

Point estimate

-0.83

Confidence interval

level

90%

sides

2-sided

lower limit

-1.69

upper limit

0.02

Variability estimate

Standard error of the mean

Dispersion value

0.52

Notes
[39] - 2-sided p-value; alpha=0.10.

Secondary: Erosion Scores at Months 6 and 12

Top of page

End point title

Erosion Scores at Months 6 and 12

End point description

Erosion score (a component of the modified TSS) is a measure of change in joint health. Erosion score range is from 0 (no erosion) to 280 (high erosion). Increase from baseline represents disease progression and / or joint worsening; no change represents halting of disease progression; a decrease represents improvement. Evaluable Set; n=number of subjects assessed for the specified parameter at a given visit.

End point type

Secondary

End point timeframe

Months 6, 12

End point values	Tofacitinib (CP- 690,550) Plus Methotrexate (MTX)	Tofacitinib (CP- 690,550)	Methotrexate
Number of subjects analysed	29	27	28
Units: scores on a scale
least squares mean (standard error)
Month 6 (n=29,27,28)	5.84 ± 0.24	5.59 ± 0.25	6.26 ± 0.25
Month 12 (n=26,25,22)	6.1 ± 0.25	5.64 ± 0.26	6.33 ± 0.27

Tofacitinib Plus MTX vs MTX at Month 6

Comparison groups

Tofacitinib (CP- 690,550) Plus Methotrexate (MTX) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.2351 ^[40]

Method

mixed model repeated measures analysis

Parameter type

Difference in LS Means

Point estimate

-0.42

Confidence interval

level

90%

sides

2-sided

lower limit

-1

upper limit

0.16

Variability estimate

Standard error of the mean

Dispersion value

0.35

Notes
[40] - 2-sided p-value; alpha=0.10.

Tofacitinib vs MTX at Month 6

Comparison groups

Tofacitinib (CP- 690,550) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.0631 ^[41]

Method

mixed model repeated measures analysis

Parameter type

Difference in LS Means

Point estimate

-0.67

Confidence interval

level

90%

sides

2-sided

lower limit

-1.27

upper limit

-0.08

Variability estimate

Standard error of the mean

Dispersion value

0.36

Notes
[41] - 2-sided p-value; alpha=0.10.

Tofacitinib Plus MTX vs MTX at Month 12

Comparison groups

Tofacitinib (CP- 690,550) Plus Methotrexate (MTX) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.5369 ^[42]

Method

mixed model repeated measures analysis

Parameter type

Difference in LS Means

Point estimate

-0.23

Confidence interval

level

90%

sides

2-sided

lower limit

-0.83

upper limit

0.38

Variability estimate

Standard error of the mean

Dispersion value

0.36

Notes
[42] - 2-sided p-value; alpha=0.10.

Tofacitinib vs MTX at Month 12

Comparison groups

Tofacitinib (CP- 690,550) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.062 ^[43]

Method

mixed model repeated measures analysis

Parameter type

Difference in LS Means

Point estimate

-0.69

Confidence interval

level

90%

sides

2-sided

lower limit

-1.31

upper limit

-0.08

Variability estimate

Standard error of the mean

Dispersion value

0.37

Notes
[43] - 2-sided p-value; alpha=0.10.

Secondary: Change From Baseline to Months 6 and 12 in Erosion Score

Top of page

End point title

Change From Baseline to Months 6 and 12 in Erosion Score

End point description

End point type

Secondary

End point timeframe

Months 6, 12

End point values	Tofacitinib (CP- 690,550) Plus Methotrexate (MTX)	Tofacitinib (CP- 690,550)	Methotrexate
Number of subjects analysed	29	27	28
Units: scores on a scale
least squares mean (standard error)
Month 6 (n=29,27,28)	0.16 ± 0.24	-0.1 ± 0.25	0.58 ± 0.25
Month 12 (n=26,25,22)	0.42 ± 0.25	-0.05 ± 0.26	0.65 ± 0.27

Tofacitinib Plus MTX vs MTX at Month 6

Comparison groups

Tofacitinib (CP- 690,550) Plus Methotrexate (MTX) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.2351 ^[44]

Method

mixed model repeated measures analysis

Parameter type

Difference in LS Means

Point estimate

-0.42

Confidence interval

level

90%

sides

2-sided

lower limit

-1

upper limit

0.16

Variability estimate

Standard error of the mean

Dispersion value

0.35

Notes
[44] - 2-sided p-value; alpha=0.10.

Tofacitinib vs MTX at Month 6

Comparison groups

Tofacitinib (CP- 690,550) Plus Methotrexate (MTX) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.0631 ^[45]

Method

mixed model repeated measures analysis

Parameter type

Difference in LS Means

Point estimate

-0.67

Confidence interval

level

90%

sides

2-sided

lower limit

-1.27

upper limit

-0.08

Variability estimate

Standard error of the mean

Dispersion value

0.36

Notes
[45] - 2-sided p-value; alpha=0.10.

Tofacitinib Plus MTX vs MTX at Month 12

Comparison groups

Tofacitinib (CP- 690,550) Plus Methotrexate (MTX) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.5369 ^[46]

Method

mixed model repeated measures analysis

Parameter type

Difference in LS Means

Point estimate

-0.23

Confidence interval

level

90%

sides

2-sided

lower limit

-0.83

upper limit

0.38

Variability estimate

Standard error of the mean

Dispersion value

0.36

Notes
[46] - 2-sided p-value; alpha=0.10.

Tofacitinib vs MTX at Month 12

Comparison groups

Tofacitinib (CP- 690,550) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.062 ^[47]

Method

mixed model repeated measures analysis

Parameter type

Difference in LS Means

Point estimate

-0.69

Confidence interval

level

90%

sides

2-sided

lower limit

-1.31

upper limit

-0.08

Variability estimate

Standard error of the mean

Dispersion value

0.37

Notes
[47] - 2-sided p-value; alpha=0.10.

Secondary: Percentage of Subjects With an American College of Rheumatology (ACR) 20 Percent (%) Improvement (ACR20) Response

Top of page

End point title

Percentage of Subjects With an American College of Rheumatology (ACR) 20 Percent (%) Improvement (ACR20) Response

End point description

ACR20 response: greater than or equal to (>=) 20% improvement in tender joint count; >=20% improvement in swollen joint count; and >=20% improvement in at least 3 of 5 remaining ACR core measures: Subject's Assessment of Pain; Subject's Global Assessment of Disease Activity; Physician Global Assessment of Disease Activity; self-assessed disability (disability index of the Health Assessment Questionnaire[HAQ]);and C-Reactive Protein (CRP). FAS Non-Responder Imputation (NRI) method: subjects with missing values were considered to be non-responders. n=number of subjects assessed for the specified parameter at a given visit.

End point type

Secondary

End point timeframe

Month 1, 2, 3, 6, 9, 12

End point values	Tofacitinib (CP- 690,550) Plus Methotrexate (MTX)	Tofacitinib (CP- 690,550)	Methotrexate
Number of subjects analysed	35	36	37
Units: percentage of subjects
number (not applicable)
Month 1 (n=35,35,37)	42.86	57.14	29.73
Month 2 (n=35,36,37)	68.57	61.11	40.54
Month 3 (n=35,36,37)	77.14	61.11	48.65
Month 6 (n=35,36,37)	74.29	66.67	45.95
Month 9 (n=35,36,37)	71.43	58.33	43.24
Month 12 (n=35,36,37)	71.43	61.11	43.24

Tofacitinib Plus MTX vs MTX at Month 1

Comparison groups

Methotrexate v Tofacitinib (CP- 690,550) Plus Methotrexate (MTX)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.243

Method

Normal approximation to the binomial

Parameter type

Mean difference (final values)

Point estimate

13.12

Confidence interval

level

90%

sides

2-sided

lower limit

-5.36

upper limit

31.62

Variability estimate

Standard error of the mean

Dispersion value

11.24

Tofacitinib vs MTX at Month 1

Comparison groups

Tofacitinib (CP- 690,550) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.0147

Method

Normal approximation to the binomial

Parameter type

Mean difference (final values)

Point estimate

27.41

Confidence interval

level

90%

sides

2-sided

lower limit

8.91

upper limit

45.9

Variability estimate

Standard error of the mean

Dispersion value

11.24

Tofacitinib Plus MTX vs MTX at Month 2

Comparison groups

Tofacitinib (CP- 690,550) Plus Methotrexate (MTX) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.0127

Method

Normal approximation to the binomial

Parameter type

Mean difference (final values)

Point estimate

28.03

Confidence interval

level

90%

sides

2-sided

lower limit

9.51

upper limit

46.54

Variability estimate

Standard error of the mean

Dispersion value

11.25

Tofacitinib vs MTX at Month 2

Comparison groups

Tofacitinib (CP- 690,550) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.0724

Method

Normal approximation to the binomial

Parameter type

Mean difference (final values)

Point estimate

20.57

Confidence interval

level

90%

sides

2-sided

lower limit

1.73

upper limit

39.41

Variability estimate

Standard error of the mean

Dispersion value

11.45

Tofacitinib Plus MTX vs MTX at Month 3

Comparison groups

Tofacitinib (CP- 690,550) Plus Methotrexate (MTX) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.0086

Method

Normal approximation to the binomial

Parameter type

Mean difference (final values)

Point estimate

28.49

Confidence interval

level

90%

sides

2-sided

lower limit

10.63

upper limit

46.35

Variability estimate

Standard error of the mean

Dispersion value

10.85

Tofacitinib vs MTX at Month 3

Comparison groups

Tofacitinib (CP- 690,550) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.2808

Method

Normal approximation to the binomial

Parameter type

Mean difference (final values)

Point estimate

12.46

Confidence interval

level

90%

sides

2-sided

lower limit

-6.54

upper limit

31.47

Variability estimate

Standard error of the mean

Dispersion value

11.55

Tofacitinib Plus MTX vs MTX at Month 6

Comparison groups

Tofacitinib (CP- 690,550) Plus Methotrexate (MTX) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.0102

Method

Normal approximation to the binomial

Parameter type

Mean difference (final values)

Point estimate

28.33

Confidence interval

level

90%

sides

2-sided

lower limit

10.19

upper limit

46.48

Variability estimate

Standard error of the mean

Dispersion value

11.03

Tofacitinib vs MTX at Month 6

Comparison groups

Tofacitinib (CP- 690,550) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.0679

Method

Normal approximation to the binomial

Parameter type

Mean difference (final values)

Point estimate

20.72

Confidence interval

level

90%

sides

2-sided

lower limit

2.04

upper limit

39.39

Variability estimate

Standard error of the mean

Dispersion value

11.35

Tofacitinib Plus MTX vs MTX at Month 9

Comparison groups

Tofacitinib (CP- 690,550) Plus Methotrexate (MTX) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.0115

Method

Normal approximation to the binomial

Parameter type

Mean difference (final values)

Point estimate

28.18

Confidence interval

level

90%

sides

2-sided

lower limit

9.81

upper limit

46.55

Variability estimate

Standard error of the mean

Dispersion value

11.16

Tofacitinib vs MTX at Month 9

Comparison groups

Tofacitinib (CP- 690,550) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.1921

Method

Normal approximation to the binomial

Parameter type

Median difference (final values)

Point estimate

15.09

Confidence interval

level

90%

sides

2-sided

lower limit

-3.94

upper limit

34.12

Variability estimate

Standard error of the mean

Dispersion value

11.56

Tofacitinib Plus MTX vs MTX at Month 12

Comparison groups

Tofacitinib (CP- 690,550) Plus Methotrexate (MTX) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.0115

Method

Normal approximation to the binomial

Parameter type

Mean difference (final values)

Point estimate

28.18

Confidence interval

level

90%

sides

2-sided

lower limit

9.81

upper limit

46.55

Variability estimate

Standard error of the mean

Dispersion value

11.16

Tofacitinib vs MTX at Month 12

Comparison groups

Tofacitinib (CP- 690,550) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.1203

Method

Normal approximation to the binomial

Parameter type

Mean difference (final values)

Point estimate

17.86

Confidence interval

level

90%

sides

2-sided

lower limit

-1.05

upper limit

36.79

Variability estimate

Standard error of the mean

Dispersion value

11.5

Secondary: Percentage of Subjects With an ACR 50% Improvement (ACR50) Response

Top of page

End point title

Percentage of Subjects With an ACR 50% Improvement (ACR50) Response

End point description

ACR50 response: >=50% improvement in tender or swollen joint counts and 50% improvement in 3 of the following 5 criteria: 1) Physician's Global Assessment of Disease Activity, 2) Subject's Assessment of disease activity, 3) Subject's Assessment of Pain, 4) Subject's assessment of functional disability via a HAQ, and 5) CRP at each visit. FAS NRI; n=number of subjects assess for the specified parameter at a given visit.

End point type

Secondary

End point timeframe

Month 1, 2, 3, 6, 9, 12

End point values	Tofacitinib (CP- 690,550) Plus Methotrexate (MTX)	Tofacitinib (CP- 690,550)	Methotrexate
Number of subjects analysed	35	36	37
Units: percentage of subjects
number (not applicable)
Month 1 (n=35,35,37)	22.86	22.86	2.7
Month 2 (n=35,36,37)	45.71	33.33	16.22
Month 3 (n=35,36,37)	48.57	50	24.32
Month 6 (n=35,36,37)	57.14	47.22	21.62
Month 9 (n=35,36,37)	57.14	44.44	29.73
Month 12 (n=35,36,37)	57.14	44.44	29.73

Tofacitinib Plus MTX vs MTX at Month 1

Comparison groups

Tofacitinib (CP- 690,550) Plus Methotrexate (MTX) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.0078

Method

Normal approximation to the binomial

Parameter type

Mean difference (final values)

Point estimate

20.15

Confidence interval

level

90%

sides

2-sided

lower limit

7.68

upper limit

32.62

Variability estimate

Standard error of the mean

Dispersion value

7.58

Tofacitinib vs MTX at Month 1

Comparison groups

Tofacitinib (CP- 690,550) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.0078

Method

Normal approximation to the binomial

Parameter type

Mean difference (final values)

Point estimate

20.15

Confidence interval

level

90%

sides

2-sided

lower limit

7.68

upper limit

32.62

Variability estimate

Standard error of the mean

Dispersion value

7.58

Tofacitinib Plus MTX vs MTX at Month 2

Comparison groups

Tofacitinib (CP- 690,550) Plus Methotrexate (MTX) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.0044

Method

Normal approximation to the binomial

Parameter type

Mean difference (final values)

Point estimate

29.49

Confidence interval

level

90%

sides

2-sided

lower limit

12.43

upper limit

46.56

Variability estimate

Standard error of the mean

Dispersion value

10.37

Tofacitinib vs MTX at Month 2

Comparison groups

Tofacitinib (CP- 690,550) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.0845

Method

Normal approximation to the binomial

Parameter type

Mean difference (final values)

Point estimate

17.11

Confidence interval

level

90%

sides

2-sided

lower limit

0.79

upper limit

33.43

Variability estimate

Standard error of the mean

Dispersion value

9.92

Tofacitinib Plus MTX vs MTX at Month 3

Comparison groups

Tofacitinib (CP- 690,550) Plus Methotrexate (MTX) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.0275

Method

Normal approximation to the binomial

Parameter type

Mean difference (final values)

Point estimate

24.24

Confidence interval

level

90%

sides

2-sided

lower limit

6.14

upper limit

42.35

Variability estimate

Standard error of the mean

Dispersion value

Tofacitinib vs MTX at Month 3

Comparison groups

Tofacitinib (CP- 690,550) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.0186

Method

Normal approximation to the binomial

Parameter type

Mean difference (final values)

Point estimate

25.67

Confidence interval

level

90%

sides

2-sided

lower limit

7.71

upper limit

43.63

Variability estimate

Standard error of the mean

Dispersion value

10.91

Tofacitinib Plus MTX vs MTX at Month 6

Comparison groups

Tofacitinib (CP- 690,550) Plus Methotrexate (MTX) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.0009

Method

Normal approximation to the binomial

Parameter type

Mean difference (final values)

Point estimate

35.52

Confidence interval

level

90%

sides

2-sided

lower limit

17.82

upper limit

53.22

Variability estimate

Standard error of the mean

Dispersion value

10.75

Tofacitinib vs MTX at Month 6

Comparison groups

Tofacitinib (CP- 690,550) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.0169

Method

Normal approximation to the binomial

Parameter type

Mean difference (final values)

Point estimate

25.6

Confidence interval

level

90%

sides

2-sided

lower limit

7.95

upper limit

43.24

Variability estimate

Standard error of the mean

Dispersion value

10.72

Tofacitinib Plus MTX vs MTX at Month 9

Comparison groups

Tofacitinib (CP- 690,550) Plus Methotrexate (MTX) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.0147

Method

Normal approximation to the binomial

Parameter type

Mean difference (final values)

Point estimate

27.41

Confidence interval

level

90%

sides

2-sided

lower limit

8.91

upper limit

45.9

Variability estimate

Standard error of the mean

Dispersion value

11.24

Tofacitinib vs MTX at Month 9

Comparison groups

Tofacitinib (CP- 690,550) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.1882

Method

Normal approximation to the binomial

Parameter type

Mean difference (final values)

Point estimate

14.71

Confidence interval

level

90%

sides

2-sided

lower limit

-3.68

upper limit

33.11

Variability estimate

Standard error of the mean

Dispersion value

11.18

Tofacitinib Plus MTX vs MTX at Month 12

Comparison groups

Tofacitinib (CP- 690,550) Plus Methotrexate (MTX) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.0147

Method

Normal approximation to the binomial

Parameter type

Mean difference (final values)

Point estimate

27.41

Confidence interval

level

90%

sides

2-sided

lower limit

8.91

upper limit

45.9

Variability estimate

Standard error of the mean

Dispersion value

11.24

Tofacitinib vs MTX at Month 12

Comparison groups

Tofacitinib (CP- 690,550) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.1882

Method

Normal approximation to the binomial

Parameter type

Mean difference (final values)

Point estimate

14.71

Confidence interval

level

90%

sides

2-sided

lower limit

-3.68

upper limit

33.11

Variability estimate

Standard error of the mean

Dispersion value

11.18

Secondary: Percentage of Subjects With an ACR 70% Improvement (ACR70) Response

Top of page

End point title

Percentage of Subjects With an ACR 70% Improvement (ACR70) Response

End point description

ACR70 response: >=70% improvement in tender or swollen joint counts and 70% improvement in 3 of the following 5 criteria: 1) Physician's Global Assessment of Disease Activity, 2) Subject's Assessment of Disease Activity, 3) Subject's Assessment of Pain, 4) Subject's Assessment of Functional Disability via a HAQ, and 5) CRP at each visit. FAS NRI; n=number of subjects assessed for the specified parameter at a given visit.

End point type

Secondary

End point timeframe

Month 1, 2, 3, 6, 9, 12

End point values	Tofacitinib (CP- 690,550) Plus Methotrexate (MTX)	Tofacitinib (CP- 690,550)	Methotrexate
Number of subjects analysed	35	36	37
Units: percentage of subjects
number (not applicable)
Month 1 (n=35,35,37)	8.57	2.86	0
Month 2 (n=35,36,37)	31.43	22.22	5.41
Month 3 (n=35,36,37)	25.71	27.78	10.81
Month 6 (n=35,36,37)	34.29	30.56	21.62
Month 9 (n=35,36,37)	31.43	33.33	18.92
Month 12 (n=35,36,37)	22.86	33.33	21.62

Tofacitinib Plus MTX vs MTX at Month 1

Comparison groups

Tofacitinib (CP- 690,550) Plus Methotrexate (MTX) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.07

Method

Normal approximation to the binomial

Parameter type

Mean difference (final values)

Point estimate

8.57

Confidence interval

level

90%

sides

2-sided

lower limit

0.78

upper limit

16.35

Variability estimate

Standard error of the mean

Dispersion value

4.73

Tofacitinib vs MTX at Month 1

Comparison groups

Tofacitinib (CP- 690,550) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.3102

Method

Normal approximation to the binomial

Parameter type

Mean difference (final values)

Point estimate

2.85

Confidence interval

level

90%

sides

2-sided

lower limit

-1.77

upper limit

7.48

Variability estimate

Standard error of the mean

Dispersion value

2.81

Tofacitinib Plus MTX vs MTX at Month 2

Comparison groups

Tofacitinib (CP- 690,550) Plus Methotrexate (MTX) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.0027

Method

Normal approximation to the binomial

Parameter type

Mean difference (final values)

Point estimate

26.02

Confidence interval

level

90%

sides

2-sided

lower limit

11.73

upper limit

40.3

Variability estimate

Standard error of the mean

Dispersion value

8.68

Tofacitinib vs MTX at Month 2

Comparison groups

Tofacitinib (CP- 690,550) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.0324

Method

Normal approximation to the binomial

Parameter type

Mean difference (final values)

Point estimate

16.81

Confidence interval

level

90%

sides

2-sided

lower limit

3.88

upper limit

29.75

Variability estimate

Standard error of the mean

Dispersion value

7.86

Tofacitinib Plus MTX vs MTX at Month 3

Comparison groups

Tofacitinib (CP- 690,550) Plus Methotrexate (MTX) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.0969

Method

Normal approximation to the binomial

Parameter type

Mean difference (final values)

Point estimate

14.9

Confidence interval

level

90%

sides

2-sided

lower limit

0.13

upper limit

29.67

Variability estimate

Standard error of the mean

Dispersion value

8.97

Tofacitinib vs MTX at Month 3

Comparison groups

Tofacitinib (CP- 690,550) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.0606

Method

Normal approximation to the binomial

Parameter type

Mean difference (final values)

Point estimate

16.96

Confidence interval

level

90%

sides

2-sided

lower limit

2.09

upper limit

31.84

Variability estimate

Standard error of the mean

Dispersion value

9.04

Tofacitinib Plus MTX vs MTX at Month 6

Comparison groups

Tofacitinib (CP- 690,550) Plus Methotrexate (MTX) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.2276

Method

Normal approximation to the binomial

Parameter type

Mean difference (net)

Point estimate

12.66

Confidence interval

level

90%

sides

2-sided

lower limit

-4.6

upper limit

29.93

Variability estimate

Standard error of the mean

Dispersion value

10.49

Tofacitinib vs MTX at Month 6

Comparison groups

Tofacitinib (CP- 690,550) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.3827

Method

Normal approximation to the binomial

Parameter type

Mean difference (final values)

Point estimate

8.93

Confidence interval

level

90%

sides

2-sided

lower limit

-7.9

upper limit

25.76

Variability estimate

Standard error of the mean

Dispersion value

10.23

Tofacitinib Plus MTX vs MTX at Month 9

Comparison groups

Tofacitinib (CP- 690,550) Plus Methotrexate (MTX) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.2177

Method

Normal approximation to the binomial

Parameter type

Mean difference (final values)

Point estimate

12.5

Confidence interval

level

90%

sides

2-sided

lower limit

-4.18

upper limit

29.2

Variability estimate

Standard error of the mean

Dispersion value

10.15

Tofacitinib vs MTX at Month 9

Comparison groups

Tofacitinib (CP- 690,550) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.1558

Method

Normal approximation to the binomial

Parameter type

Mean difference (final values)

Point estimate

14.41

Confidence interval

level

90%

sides

2-sided

lower limit

-2.29

upper limit

31.12

Variability estimate

Standard error of the mean

Dispersion value

10.15

Tofacitinib Plus MTX vs MTX at Month 12

Comparison groups

Tofacitinib (CP- 690,550) Plus Methotrexate (MTX) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.8997

Method

Normal approximation to the binomial

Parameter type

Mean difference (final values)

Point estimate

1.23

Confidence interval

level

90%

sides

2-sided

lower limit

-14.89

upper limit

17.36

Variability estimate

Standard error of the mean

Dispersion value

9.8

Tofacitinib vs MTX at Month 12

Comparison groups

Tofacitinib (CP- 690,550) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.2587

Method

Normal approximation to the binomial

Parameter type

Mean difference (final values)

Point estimate

11.71

Confidence interval

level

90%

sides

2-sided

lower limit

-5.34

upper limit

28.76

Variability estimate

Standard error of the mean

Dispersion value

10.36

Secondary: Disease Activity Score Based on 28-Joint Count and CRP (DAS28-3 [CRP])

Top of page

End point title

Disease Activity Score Based on 28-Joint Count and CRP (DAS28-3 [CRP])

End point description

DAS28-3 (CRP) was calculated from the swollen joint count and tender joint count using the 28 joints count and CRP (mg/L). Total score range: 0 to 9.4, higher score indicated more disease activity. DAS28-3 (CRP) less than or equal to (<=) 3.2 implied low disease activity and greater than (>) 3.2 to 5.1 implied moderate to high disease activity, and DAS28-3 (CRP) less than (<) 2.6 = remission. FAS; n=number of subjects assessed for the specified parameter at a given visit.

End point type

Secondary

End point timeframe

Baseline, Month 1, 2, 3, 6, 9, 12

End point values	Tofacitinib (CP- 690,550) Plus Methotrexate (MTX)	Tofacitinib (CP- 690,550)	Methotrexate
Number of subjects analysed	36	36	37
Units: score on a scale
arithmetic mean (standard deviation)
Baseline (n=36,36,37)	5.14 ± 0.96	5.48 ± 0.78	5.36 ± 0.8
Month 1 (n=33,35,37)	3.71 ± 1.15	4.03 ± 0.91	4.65 ± 1.07
Month 2 (n=33,33,32)	2.99 ± 1.17	3.52 ± 1.15	4.21 ± 1.31
Month 3 (n=33,33,31)	3.06 ± 1.02	3.46 ± 1.09	3.87 ± 1.43
Month 6 (n=31,29,29)	2.74 ± 1.15	2.75 ± 0.95	3.92 ± 1.49
Month 9 (n=30,28,24)	2.37 ± 0.98	2.85 ± 0.9	3.58 ± 1.63
Month 12 (n=27,26,20)	2.49 ± 1.02	2.68 ± 1.05	3.58 ± 1.4

Tofacitinib Plus MTX vs MTX at Baseline

Comparison groups

Tofacitinib (CP- 690,550) Plus Methotrexate (MTX) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (final values)

Point estimate

-0.22

Confidence interval

level

90%

sides

2-sided

lower limit

-0.56

upper limit

0.13

Tofacitinib vs MTX at Baseline

Comparison groups

Tofacitinib (CP- 690,550) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (final values)

Point estimate

0.12

Confidence interval

level

90%

sides

2-sided

lower limit

-0.19

upper limit

0.43

Tofacitinib Plus MTX vs MTX at Month 1

Comparison groups

Tofacitinib (CP- 690,550) Plus Methotrexate (MTX) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (final values)

Point estimate

-0.94

Confidence interval

level

90%

sides

2-sided

lower limit

-1.38

upper limit

-0.5

Tofacitinib vs MTX at Month 1

Comparison groups

Tofacitinib (CP- 690,550) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (final values)

Point estimate

-0.62

Confidence interval

level

90%

sides

2-sided

lower limit

-1.01

upper limit

-0.22

Tofacitinib Plus MTX vs MTX at Month 2

Comparison groups

Tofacitinib (CP- 690,550) Plus Methotrexate (MTX) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (final values)

Point estimate

-1.21

Confidence interval

level

90%

sides

2-sided

lower limit

-1.73

upper limit

-0.7

Tofacitinib vs MTX at Month 2

Comparison groups

Tofacitinib (CP- 690,550) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (final values)

Point estimate

-0.69

Confidence interval

level

90%

sides

2-sided

lower limit

-1.2

upper limit

-0.18

Tofacitinib Plus MTX vs MTX at Month 3

Comparison groups

Tofacitinib (CP- 690,550) Plus Methotrexate (MTX) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (final values)

Point estimate

-0.81

Confidence interval

level

90%

sides

2-sided

lower limit

-1.33

upper limit

-0.29

Tofacitinib vs MTX at Month 3

Comparison groups

Tofacitinib (CP- 690,550) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (final values)

Point estimate

-0.41

Confidence interval

level

90%

sides

2-sided

lower limit

-0.94

upper limit

0.12

Tofacitinib Plus MTX vs MTX at Month 6

Comparison groups

Tofacitinib (CP- 690,550) Plus Methotrexate (MTX) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (final values)

Point estimate

-1.18

Confidence interval

level

90%

sides

2-sided

lower limit

-1.75

upper limit

-0.61

Tofacitinib vs MTX at Month 6

Comparison groups

Tofacitinib (CP- 690,550) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (final values)

Point estimate

-1.18

Confidence interval

level

90%

sides

2-sided

lower limit

-1.73

upper limit

-0.63

Tofacitinib Plus MTX vs MTX at Month 9

Comparison groups

Tofacitinib (CP- 690,550) Plus Methotrexate (MTX) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (final values)

Point estimate

-1.21

Confidence interval

level

90%

sides

2-sided

lower limit

-1.81

upper limit

-0.61

Tofacitinib vs MTX at Month 9

Comparison groups

Tofacitinib (CP- 690,550) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (final values)

Point estimate

-0.73

Confidence interval

level

90%

sides

2-sided

lower limit

-1.33

upper limit

-0.13

Tofacitinib Plus MTX vs MTX at Month 12

Comparison groups

Tofacitinib (CP- 690,550) Plus Methotrexate (MTX) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (final values)

Point estimate

-1.1

Confidence interval

level

90%

sides

2-sided

lower limit

-1.69

upper limit

-0.51

Tofacitinib vs MTX at Month 12

Comparison groups

Tofacitinib (CP- 690,550) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (final values)

Point estimate

-0.9

Confidence interval

level

90%

sides

2-sided

lower limit

-1.51

upper limit

-0.29

Secondary: Change From Baseline in DAS28-3 (CRP)

Top of page

End point title

Change From Baseline in DAS28-3 (CRP)

End point description

End point type

Secondary

End point timeframe

Month 1, 2, 3, 6, 9, 12

End point values	Tofacitinib (CP- 690,550) Plus Methotrexate (MTX)	Tofacitinib (CP- 690,550)	Methotrexate
Number of subjects analysed	33	35	37
Units: scores on a scale
least squares mean (standard error)
Month 1 (n=33,35,37)	-1.61 ± 0.19	-1.4 ± 0.18	-0.73 ± 0.18
Month 2 (n=33,33,32)	-2.32 ± 0.19	-1.88 ± 0.19	-1.24 ± 0.19
Month 3 (n=33,33,31)	-2.25 ± 0.19	-1.96 ± 0.19	-1.57 ± 0.19
Month 6 (n=31,29,29)	-2.54 ± 0.19	-2.55 ± 0.2	-1.52 ± 0.19
Month 9 (n=30,28,24)	-2.92 ± 0.2	-2.43 ± 0.2	-1.76 ± 0.21
Month 12 (n=27,26,20)	-2.78 ± 0.2	-2.61 ± 0.2	-1.77 ± 0.22

Tofacitinib Plus MTX vs MTX at Month 1

Comparison groups

Tofacitinib (CP- 690,550) Plus Methotrexate (MTX) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.001 ^[48]

Method

mixed model repeated measures analysis

Parameter type

Difference in LS Means

Point estimate

-0.88

Confidence interval

level

90%

sides

2-sided

lower limit

-1.31

upper limit

-0.45

Variability estimate

Standard error of the mean

Dispersion value

0.26

Notes
[48] - 2-sided p-value; alpha=0.10.

Tofacitinib vs MTX at Month 1

Comparison groups

Tofacitinib (CP- 690,550) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.0102 ^[49]

Method

mixed model repeated measures analysis

Parameter type

Difference in LS Means

Point estimate

-0.67

Confidence interval

level

90%

sides

2-sided

lower limit

-1.1

upper limit

-0.24

Variability estimate

Standard error of the mean

Dispersion value

0.26

Notes
[49] - 2-sided p-value; alpha=0.10

Tofacitinib Plus MTX vs MTX at Month 2

Comparison groups

Tofacitinib (CP- 690,550) Plus Methotrexate (MTX) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.0001 ^[50]

Method

mixed model repeated measures analysis

Parameter type

Difference in LS Means

Point estimate

-1.08

Confidence interval

level

90%

sides

2-sided

lower limit

-1.52

upper limit

-0.64

Variability estimate

Standard error of the mean

Dispersion value

0.27

Notes
[50] - 2-sided p-value; alpha=0.10.

Tofacitinib vs MTX at Month 2

Comparison groups

Tofacitinib (CP- 690,550) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.0175 ^[51]

Method

mixed model repeated measures analysis

Parameter type

Difference in LS Means

Point estimate

-0.64

Confidence interval

level

90%

sides

2-sided

lower limit

-1.08

upper limit

-0.2

Variability estimate

Standard error of the mean

Dispersion value

0.27

Notes
[51] - 2-sided p-value; alpha=0.10.

Tofacitinib Plus MTX vs MTX at Month 3

Comparison groups

Tofacitinib (CP- 690,550) Plus Methotrexate (MTX) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.0125 ^[52]

Method

mixed model repeated measures analysis

Parameter type

Difference in LS Means

Point estimate

-0.68

Confidence interval

level

90%

sides

2-sided

lower limit

-1.13

upper limit

-0.23

Variability estimate

Standard error of the mean

Dispersion value

0.27

Notes
[52] - 2-sided p-value; alpha=0.10.

Tofacitinib vs MTX at Month 3

Comparison groups

Tofacitinib (CP- 690,550) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.1457 ^[53]

Method

mixed model repeated measures analysis

Parameter type

Difference in LS Means

Point estimate

-0.39

Confidence interval

level

90%

sides

2-sided

lower limit

-0.84

upper limit

0.05

Variability estimate

Standard error of the mean

Dispersion value

0.27

Notes
[53] - 2-sided p-value; alpha=0.10.

Tofacitinib Plus MTX vs MTX at Month 6

Comparison groups

Tofacitinib (CP- 690,550) Plus Methotrexate (MTX) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.0003 ^[54]

Method

mixed model repeated measures analysis

Parameter type

Difference in LS Means

Point estimate

-1.02

Confidence interval

level

90%

sides

2-sided

lower limit

-1.48

upper limit

-0.57

Variability estimate

Standard error of the mean

Dispersion value

0.28

Notes
[54] - 2-sided p-value; alpha=0.10

Tofacitinib vs MTX at Month 6

Comparison groups

Tofacitinib (CP- 690,550) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.0002 ^[55]

Method

Difference in LS Means

Parameter type

Mean difference (final values)

Point estimate

-1.03

Confidence interval

level

90%

sides

2-sided

lower limit

-1.49

upper limit

-0.58

Variability estimate

Standard error of the mean

Dispersion value

0.28

Notes
[55] - 2-sided p-value; alpha=0.10.

Tofacitinib Plus MTX vs MTX at Month 9

Comparison groups

Tofacitinib (CP- 690,550) Plus Methotrexate (MTX) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.0001 ^[56]

Method

mixed model repeated measures analysis

Parameter type

Difference in LS Means

Point estimate

-1.16

Confidence interval

level

90%

sides

2-sided

lower limit

-1.63

upper limit

-0.69

Variability estimate

Standard error of the mean

Dispersion value

0.28

Notes
[56] - 2-sided p-value; alpha=0.10.

Tofacitinib vs MTX at Month 9

Comparison groups

Tofacitinib (CP- 690,550) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.0196 ^[57]

Method

mixed model repeated measures analysis

Parameter type

Difference in LS Means

Point estimate

-0.67

Confidence interval

level

90%

sides

2-sided

lower limit

-1.14

upper limit

-0.2

Variability estimate

Standard error of the mean

Dispersion value

0.28

Notes
[57] - 2-sided p-value; alpha=0.10.

Tofacitinib Plus MTX vs MTX at Month 12

Comparison groups

Tofacitinib (CP- 690,550) Plus Methotrexate (MTX) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.0007 ^[58]

Method

mixed model repeated measures analysis

Parameter type

Difference in LS Means

Point estimate

-1.01

Confidence interval

level

90%

sides

2-sided

lower limit

-1.5

upper limit

-0.52

Variability estimate

Standard error of the mean

Dispersion value

0.3

Notes
[58] - 2-sided p-value; alpha=0.10.

Tofacitinib vs MTX at Month 12

Comparison groups

Tofacitinib (CP- 690,550) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.0049 ^[59]

Method

mixed model repeated measures analysis

Parameter type

Mean difference (final values)

Point estimate

-0.84

Confidence interval

level

90%

sides

2-sided

lower limit

-1.32

upper limit

-0.35

Variability estimate

Standard error of the mean

Dispersion value

0.3

Notes
[59] - 2-sided p-value; alpha=0.10.

Secondary: Disease Activity Score Based on 28-Joint Count and Erythrocyte Sedimentation Rate (DAS28-4 [ESR])

Top of page

End point title

Disease Activity Score Based on 28-Joint Count and Erythrocyte Sedimentation Rate (DAS28-4 [ESR])

End point description

DAS28-4 (ESR) was calculated from swollen joint count and tender joint count using 28 joints count, ESR (millimeters per hour [mm/hour]) and Subject Global Assessment of disease activity (subject rated arthritis activity assessment). Total score range: 0 to 9.4; higher score=more disease activity. DAS28-4 (ESR) =<3.2 implied low disease activity and >3.2 to 5.1 implied moderate to high disease activity, and DAS28-4 (ESR) <2.6 = remission. FAS; n=number of subjects assessed for the specified parameter at a given visit.

End point type

Secondary

End point timeframe

Baseline, Month 1, 2, 3, 6, 9, 12

End point values	Tofacitinib (CP- 690,550) Plus Methotrexate (MTX)	Tofacitinib (CP- 690,550)	Methotrexate
Number of subjects analysed	36	36	37
Units: scores on a scale
arithmetic mean (standard deviation)
Baseline (n=36,36,37)	6.25 ± 0.94	6.5 ± 0.75	6.44 ± 0.78
Month 1 (n=34,35,37)	4.6 ± 1.37	4.93 ± 1.12	5.51 ± 1.09
Month 2 (n=32,33,31)	3.77 ± 1.34	4.36 ± 1.4	5.05 ± 1.26
Month 3 (n=33,33,31)	3.66 ± 1.16	4.12 ± 1.31	4.63 ± 1.63
Month 6 (n=30,29,28)	3.32 ± 1.45	3.51 ± 1.2	4.75 ± 1.76
Month 9 (n=30,28,24)	3.06 ± 1.27	3.58 ± 1.1	4.17 ± 1.91
Month 12 (n=27,26,20)	3.02 ± 1.22	3.47 ± 1.36	4.13 ± 1.76

Tofacitinib Plus MTX vs MTX at Baseline

Comparison groups

Tofacitinib (CP- 690,550) Plus Methotrexate (MTX) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (final values)

Point estimate

-0.19

Confidence interval

level

90%

sides

2-sided

lower limit

-0.53

upper limit

0.15

Tofacitinib vs MTX at Baseline

Comparison groups

Tofacitinib (CP- 690,550) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (final values)

Point estimate

0.06

Confidence interval

level

90%

sides

2-sided

lower limit

-0.24

upper limit

0.36

Tofacitinib Plus MTX vs MTX at Month 1

Comparison groups

Tofacitinib (CP- 690,550) Plus Methotrexate (MTX) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (final values)

Point estimate

-0.91

Confidence interval

level

90%

sides

2-sided

lower limit

-1.4

upper limit

-0.42

Tofacitinib vs MTX at Month 1

Comparison groups

Tofacitinib (CP- 690,550) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (final values)

Point estimate

-0.58

Confidence interval

level

90%

sides

2-sided

lower limit

-1.01

upper limit

-0.14

Tofacitinib Plus MTX vs MTX at Month 2

Comparison groups

Tofacitinib (CP- 690,550) Plus Methotrexate (MTX) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (final values)

Point estimate

-1.28

Confidence interval

level

90%

sides

2-sided

lower limit

-1.82

upper limit

-0.73

Tofacitinib vs MTX at Month 2

Comparison groups

Tofacitinib (CP- 690,550) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (final values)

Point estimate

-0.69

Confidence interval

level

90%

sides

2-sided

lower limit

-1.25

upper limit

-0.13

Tofacitinib Plus MTX vs MTX at Month 3

Comparison groups

Tofacitinib (CP- 690,550) Plus Methotrexate (MTX) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (final values)

Point estimate

-0.96

Confidence interval

level

90%

sides

2-sided

lower limit

-1.55

upper limit

-0.38

Tofacitinib vs MTX at Month 3

Comparison groups

Tofacitinib (CP- 690,550) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (final values)

Point estimate

-0.51

Confidence interval

level

90%

sides

2-sided

lower limit

-1.12

upper limit

0.11

Tofacitinib Plus MTX vs MTX at Month 6

Comparison groups

Tofacitinib (CP- 690,550) Plus Methotrexate (MTX) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (final values)

Point estimate

-1.43

Confidence interval

level

90%

sides

2-sided

lower limit

-2.13

upper limit

-0.72

Tofacitinib vs MTX at Month 6

Comparison groups

Tofacitinib (CP- 690,550) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (final values)

Point estimate

-1.24

Confidence interval

level

90%

sides

2-sided

lower limit

-1.91

upper limit

-0.57

Tofacitinib Plus MTX vs MTX at Month 9

Comparison groups

Tofacitinib (CP- 690,550) Plus Methotrexate (MTX) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (final values)

Point estimate

-1.11

Confidence interval

level

90%

sides

2-sided

lower limit

-1.84

upper limit

-0.39

Tofacitinib vs MTX at Month 9

Comparison groups

Tofacitinib (CP- 690,550) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (final values)

Point estimate

-0.59

Confidence interval

level

90%

sides

2-sided

lower limit

-1.3

upper limit

0.13

Tofacitinib Plus MTX vs MTX at Month 12

Comparison groups

Tofacitinib (CP- 690,550) Plus Methotrexate (MTX) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (final values)

Point estimate

-1.11

Confidence interval

level

90%

sides

2-sided

lower limit

-1.84

upper limit

-0.39

Tofacitinib vs MTX at Month 12

Comparison groups

Tofacitinib (CP- 690,550) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (final values)

Point estimate

-0.66

Confidence interval

level

90%

sides

2-sided

lower limit

-1.43

upper limit

0.11

Secondary: Change From Baseline in DAS28-4 (ESR)

Top of page

End point title

Change From Baseline in DAS28-4 (ESR)

End point description

DAS28-4 (ESR) was calculated from swollen joint count and tender joint count using 28 joints count, ESR (millimeters per hour [mm/hour]) and Subject Global Assessment of disease activity (subject rated arthritis activity assessment). Total score range: 0 to 9.4; higher score=more disease activity. FAS; n=number of subjects assessed for the specified parameter at a given visit.

End point type

Secondary

End point timeframe

Month 1, 2, 3, 6, 9, 12

End point values	Tofacitinib (CP- 690,550) Plus Methotrexate (MTX)	Tofacitinib (CP- 690,550)	Methotrexate
Number of subjects analysed	34	35	37
Units: scores on a scale
least squares mean (standard error)
Month 1 (n=34,35,37)	-1.77 ± 0.21	-1.57 ± 0.21	-0.94 ± 0.2
Month 2 (n=32,33,31)	-2.59 ± 0.22	-2.08 ± 0.21	-1.41 ± 0.21
Month 3 (n=33,33,31)	-2.69 ± 0.21	-2.35 ± 0.21	-1.8 ± 0.21
Month 6 (n=30,29,28)	-3.02 ± 0.22	-2.81 ± 0.22	-1.73 ± 0.22
Month 9 (n=30,28,24)	-3.29 ± 0.22	-2.72 ± 0.22	-2.14 ± 0.23
Month 12 (n=27,26,20)	-3.31 ± 0.22	-2.84 ± 0.22	-2.18 ± 0.24

Tofacitinib Plus MTX vs MTX at Month 1

Comparison groups

Tofacitinib (CP- 690,550) Plus Methotrexate (MTX) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.0046 ^[60]

Method

mixed model repeated measures analysis

Parameter type

Difference in LS Means

Point estimate

-0.84

Confidence interval

level

90%

sides

2-sided

lower limit

-1.32

upper limit

-0.35

Variability estimate

Standard error of the mean

Dispersion value

0.29

Notes
[60] - 2-sided p-value; alpha=0.10.

Tofacitinib vs MTX at Month 1

Comparison groups

Tofacitinib (CP- 690,550) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.0303 ^[61]

Method

mixed model repeated measures analysis

Parameter type

Difference in LS Means

Point estimate

-0.63

Confidence interval

level

90%

sides

2-sided

lower limit

-1.11

upper limit

-0.15

Variability estimate

Standard error of the mean

Dispersion value

0.29

Notes
[61] - 2-sided p-value; alpha=0.10.

Tofacitinib Plus MTX vs MTX at Month 2

Comparison groups

Tofacitinib (CP- 690,550) Plus Methotrexate (MTX) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.0001 ^[62]

Method

mixed model repeated measures analysis

Parameter type

Difference in LS Means

Point estimate

-1.18

Confidence interval

level

90%

sides

2-sided

lower limit

-1.69

upper limit

-0.68

Variability estimate

Standard error of the mean

Dispersion value

0.3

Notes
[62] - 2-sided p-value; alpha=0.10.

Tofacitinib vs MTX at Month 2

Comparison groups

Tofacitinib (CP- 690,550) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.0255 ^[63]

Method

mixed model repeated measures analysis

Parameter type

Difference in LS Means

Point estimate

-0.67

Confidence interval

level

90%

sides

2-sided

lower limit

-1.17

upper limit

-0.18

Variability estimate

Standard error of the mean

Dispersion value

0.3

Notes
[63] - 2-sided p-value; alpha=0.10.

Tofacitinib Plus MTX vs MTX at Month 3

Comparison groups

Tofacitinib (CP- 690,550) Plus Methotrexate (MTX) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.0035 ^[64]

Method

mixed model repeated measures analysis

Parameter type

Difference in LS Means

Point estimate

-0.89

Confidence interval

level

90%

sides

2-sided

lower limit

-1.39

upper limit

-0.39

Variability estimate

Standard error of the mean

Dispersion value

0.3

Notes
[64] - 2-sided p-value; alpha=0.10.

Tofacitinib vs MTX at Month 3

Comparison groups

Tofacitinib (CP- 690,550) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.0683 ^[65]

Method

mixed model repeated measures analysis

Parameter type

Difference in LS Means

Point estimate

-0.55

Confidence interval

level

90%

sides

2-sided

lower limit

-1.05

upper limit

-0.05

Variability estimate

Standard error of the mean

Dispersion value

0.3

Notes
[65] - 2-sided p-value; alpha=0.10.

Tofacitinib Plus MTX vs MTX at Month 6

Comparison groups

Tofacitinib (CP- 690,550) Plus Methotrexate (MTX) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.0001 ^[66]

Method

mixed model repeated measures analysis

Parameter type

Difference in LS Means

Point estimate

-1.29

Confidence interval

level

90%

sides

2-sided

lower limit

-1.81

upper limit

-0.78

Variability estimate

Standard error of the mean

Dispersion value

0.31

Notes
[66] - 2-sided p-value; alpha=0.10.

Tofacitinib vs MTX at Month 6

Comparison groups

Tofacitinib (CP- 690,550) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.0006 ^[67]

Method

mixed model repeated measures analysis

Parameter type

Difference in LS Means

Point estimate

-1.08

Confidence interval

level

90%

sides

2-sided

lower limit

-1.59

upper limit

-0.56

Variability estimate

Standard error of the mean

Dispersion value

0.31

Notes
[67] - 2-sided p-value; alpha=0.10.

Tofacitinib Plus MTX vs MTX at Month 9

Comparison groups

Tofacitinib (CP- 690,550) Plus Methotrexate (MTX) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.0004 ^[68]

Method

mixed model repeated measures analysis

Parameter type

Difference in LS Means

Point estimate

-1.15

Confidence interval

level

90%

sides

2-sided

lower limit

-1.67

upper limit

-0.62

Variability estimate

Standard error of the mean

Dispersion value

0.32

Notes
[68] - 2-sided p-value; alpha=0.10.

Tofacitinib vs MTX at Month 9

Comparison groups

Tofacitinib (CP- 690,550) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.0706 ^[69]

Method

mixed model repeated measures analysis

Parameter type

Difference in LS Means

Point estimate

-0.58

Confidence interval

level

90%

sides

2-sided

lower limit

-1.1

upper limit

-0.05

Variability estimate

Standard error of the mean

Dispersion value

0.32

Notes
[69] - 2-sided p-value; alpha=0.10.

Tofacitinib Plus MTX vs MTX at Month 12

Comparison groups

Tofacitinib (CP- 690,550) Plus Methotrexate (MTX) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.0008 ^[70]

Method

mixed model repeated measures analysis

Parameter type

Difference in LS Means

Point estimate

-1.13

Confidence interval

level

90%

sides

2-sided

lower limit

-1.67

upper limit

-0.58

Variability estimate

Standard error of the mean

Dispersion value

0.33

Notes
[70] - 2-sided p-value; alpha=0.10.

Tofacitinib vs MTX at Month 12

Comparison groups

Tofacitinib (CP- 690,550) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.0466 ^[71]

Method

mixed model repeated measures analysis

Parameter type

Difference in LS Means

Point estimate

-0.66

Confidence interval

level

90%

sides

2-sided

lower limit

-1.21

upper limit

-0.12

Variability estimate

Standard error of the mean

Dispersion value

0.33

Notes
[71] - 2-sided p-value; alpha=0.10.

Secondary: Percentage of Subjects With DAS28-3 (CRP) Response (Good or Moderate Improvement)

Top of page

End point title

Percentage of Subjects With DAS28-3 (CRP) Response (Good or Moderate Improvement)

End point description

DAS28-3(CRP) was calculated from the swollen joint count and tender joint count using 28-joints count and CRP (mg/L). Total score range: 0 to 9.4, higher score indicated more disease activity. DAS28 categorical responses define a good (absolute: <3.2 or >1.2 improvement from baseline [BL]), moderate (absolute: 3.2-5.1 or 0.6-1.2 change from BL), or no response (absolute: >5.1 or <0.6 change from BL). FAS NRI; n=number of subjects assessed for the specified parameter at a given visit.

End point type

Secondary

End point timeframe

Month 1, 2, 3, 6, 9, 12

End point values	Tofacitinib (CP- 690,550) Plus Methotrexate (MTX)	Tofacitinib (CP- 690,550)	Methotrexate
Number of subjects analysed	34	36	37
Units: percentage of subjects
number (not applicable)
Month 1 (n=33,35,37)	75.76	71.43	43.24
Month 2 (n=34,36,37)	91.18	80.56	56.76
Month 3 (n=34,36,37)	91.18	77.78	56.76
Month 6 (n=34,36,37)	88.24	77.78	54.05
Month 9 (n=34,36,37)	79.41	69.44	45.95
Month 12 (n=34,36,37)	82.35	72.22	45.95

Tofacitinib Plus MTX vs MTX at Month 1

Comparison groups

Tofacitinib (CP- 690,550) Plus Methotrexate (MTX) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.0032 ^[72]

Method

Normal approximation to the binomial

Parameter type

Mean difference (final values)

Point estimate

32.51

Confidence interval

level

90%

sides

2-sided

lower limit

14.34

upper limit

50.68

Variability estimate

Standard error of the mean

Dispersion value

11.04

Notes
[72] - 2-sided p-value; alpha=0.10.

Tofacitinib vs MTX at Month 1

Comparison groups

Tofacitinib (CP- 690,550) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.0115 ^[73]

Method

Normal approximation to the binomial

Parameter type

Mean difference (final values)

Point estimate

28.18

Confidence interval

level

90%

sides

2-sided

lower limit

9.81

upper limit

46.55

Variability estimate

Standard error of the mean

Dispersion value

11.16

Notes
[73] - 2-sided p-value; alpha=0.10.

Tofacitinib Plus MTX vs MTX at Month 2

Comparison groups

Tofacitinib (CP- 690,550) Plus Methotrexate (MTX) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.0002 ^[74]

Method

Normal approximation to the binomial

Parameter type

Mean difference (final values)

Point estimate

34.41

Confidence interval

level

90%

sides

2-sided

lower limit

18.81

upper limit

50.02

Variability estimate

Standard error of the mean

Dispersion value

9.48

Notes
[74] - 2-sided p-value; alpha=0.10.

Tofacitinib vs MTX at Month 2

Comparison groups

Tofacitinib (CP- 690,550) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.0231 ^[75]

Method

Normal approximation to the binomial

Parameter type

Mean difference (final values)

Point estimate

23.79

Confidence interval

level

90%

sides

2-sided

lower limit

6.55

upper limit

41.03

Variability estimate

Standard error of the mean

Dispersion value

10.48

Notes
[75] - 2-sided p-value; alpha=0.10.

Tofacitinib Plus MTX vs MTX at Month 3

Comparison groups

Tofacitinib (CP- 690,550) Plus Methotrexate (MTX) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.0002 ^[76]

Method

Normal approximation to the binomial

Parameter type

Mean difference (final values)

Point estimate

34.41

Confidence interval

level

90%

sides

2-sided

lower limit

18.81

upper limit

50.02

Variability estimate

Standard error of the mean

Dispersion value

9.48

Notes
[76] - 2-sided p-value; alpha=0.10.

Tofacitinib vs MTX at Month 3

Comparison groups

Tofacitinib (CP- 690,550) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.0493 ^[77]

Method

Normal approximation to the binomial

Parameter type

Mean difference (final values)

Point estimate

21.02

Confidence interval

level

90%

sides

2-sided

lower limit

3.43

upper limit

38.61

Variability estimate

Standard error of the mean

Dispersion value

10.69

Notes
[77] - 2-sided p-value; alpha=0.10.

Tofacitinib Plus MTX vs MTX at Month 6

Comparison groups

Tofacitinib (CP- 690,550) Plus Methotrexate (MTX) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.0005 ^[78]

Method

Normal approximation to the binomial

Parameter type

Mean difference (final values)

Point estimate

34.18

Confidence interval

level

90%

sides

2-sided

lower limit

17.92

upper limit

50.43

Variability estimate

Standard error of the mean

Dispersion value

9.88

Notes
[78] - 2-sided p-value; alpha=0.10.

Tofacitinib vs MTX at Month 6

Comparison groups

Tofacitinib (CP- 690,550) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.027 ^[79]

Method

Normal approximation to the binomial

Parameter type

Mean difference (final values)

Point estimate

23.72

Confidence interval

level

90%

sides

2-sided

lower limit

6.07

upper limit

41.37

Variability estimate

Standard error of the mean

Dispersion value

10.73

Notes
[79] - 2-sided p-value; alpha=0.10.

Tofacitinib Plus MTX vs MTX at Month 9

Comparison groups

Tofacitinib (CP- 690,550) Plus Methotrexate (MTX) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.0018 ^[80]

Method

Normal approximation to the binomial

Parameter type

Mean difference (final values)

Point estimate

33.46

Confidence interval

level

90%

sides

2-sided

lower limit

15.8

upper limit

51.12

Variability estimate

Standard error of the mean

Dispersion value

10.73

Notes
[80] - 2-sided p-value; alpha=0.10.

Tofacitinib vs MTX at Month 9

Comparison groups

Tofacitinib (CP- 690,550) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.0363 ^[81]

Method

Normal approximation to the binomial

Parameter type

Mean difference (final values)

Point estimate

23.49

Confidence interval

level

90%

sides

2-sided

lower limit

5.02

upper limit

41.96

Variability estimate

Standard error of the mean

Dispersion value

11.22

Notes
[81] - 2-sided p-value; alpha=0.10.

Tofacitinib Plus MTX vs MTX at Month 12

Comparison groups

Tofacitinib (CP- 690,550) Plus Methotrexate (MTX) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.0005 ^[82]

Method

Normal approximation to the binomial

Parameter type

Mean difference (final values)

Point estimate

36.4

Confidence interval

level

90%

sides

2-sided

lower limit

19.16

upper limit

53.64

Variability estimate

Standard error of the mean

Dispersion value

10.48

Notes
[82] - 2-sided p-value; alpha=0.10.

Tofacitinib vs MTX at Month 12

Comparison groups

Tofacitinib (CP- 690,550) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.0177 ^[83]

Method

Normal approximation to the binomial

Parameter type

Mean difference (final values)

Point estimate

26.27

Confidence interval

level

90%

sides

2-sided

lower limit

8.04

upper limit

44.5

Variability estimate

Standard error of the mean

Dispersion value

11.08

Notes
[83] - 2-sided p-value; alpha=0.10.

Secondary: Percentage of Subjects With DAS28-3 (CRP) Score =<3.2

Top of page

End point title

Percentage of Subjects With DAS28-3 (CRP) Score =<3.2

End point description

DAS28-3(CRP) was calculated from the swollen joint count and tender joint count using 28-joints count and CRP (mg/L). Total score range: 0 to 9.4, higher score indicated more disease activity. DAS28-3(CRP) =<3.2 implied low disease activity. FAS NRI; n=number of subjects assessed for the specified parameter at a given visit.

End point type

Secondary

End point timeframe

Month 1, 2, 3, 6, 9, 12

End point values	Tofacitinib (CP- 690,550) Plus Methotrexate (MTX)	Tofacitinib (CP- 690,550)	Methotrexate
Number of subjects analysed	34	36	37
Units: percentage of subjects
number (not applicable)
Month 1 (n=33,35,37)	33.33	17.14	10.81
Month 2 (n=34,36,37)	50	36.11	21.62
Month 3 (n=34,36,37)	50	41.67	21.62
Month 6 (n=34,36,37)	61.76	55.56	27.03
Month 9 (n=34,36,37)	64.71	58.33	29.33
Month 12 (n=34,36,37)	61.76	50	27.03

Tofacitinib Plus MTX vs MTX at Month 1

Comparison groups

Tofacitinib (CP- 690,550) Plus Methotrexate (MTX) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.0197 ^[84]

Method

Normal approximation to the binomial

Parameter type

Mean difference (final values)

Point estimate

22.52

Confidence interval

level

90%

sides

2-sided

lower limit

6.62

upper limit

38.42

Variability estimate

Standard error of the mean

Dispersion value

9.66

Notes
[84] - 2-sided p-value; alpha=0.10.

Tofacitinib vs MTX at Month 1

Comparison groups

Tofacitinib (CP- 690,550) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.4379 ^[85]

Method

Normal approximation to the binomial

Parameter type

Mean difference (final values)

Point estimate

6.33

Confidence interval

level

90%

sides

2-sided

lower limit

-7.09

upper limit

19.76

Variability estimate

Standard error of the mean

Dispersion value

8.16

Notes
[85] - 2-sided p-value; alpha=0.10.

Tofacitinib Plus MTX vs MTX at Month 2

Comparison groups

Tofacitinib (CP- 690,550) Plus Methotrexate (MTX) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.0093 ^[86]

Method

Normal approximation to the binomial

Parameter type

Mean difference (final values)

Point estimate

28.37

Confidence interval

level

90%

sides

2-sided

lower limit

10.4

upper limit

46.34

Variability estimate

Standard error of the mean

Dispersion value

10.92

Notes
[86] - 2-sided p-value; alpha=0.10.

Tofacitinib vs MTX at Month 2

Comparison groups

Tofacitinib (CP- 690,550) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.1669 ^[87]

Method

Normal approximation to the binomial

Parameter type

Mean difference (final values)

Point estimate

14.48

Confidence interval

level

90%

sides

2-sided

lower limit

-2.75

upper limit

31.73

Variability estimate

Standard error of the mean

Dispersion value

10.48

Notes
[87] - 2-sided p-value; alpha=0.10.

Tofacitinib Plus MTX vs MTX at Month 3

Comparison groups

Tofacitinib (CP- 690,550) Plus Methotrexate (MTX) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.0093 ^[88]

Method

Normal approximation to the binomial

Parameter type

Mean difference (final values)

Point estimate

28.37

Confidence interval

level

90%

sides

2-sided

lower limit

10.4

upper limit

46.34

Variability estimate

Standard error of the mean

Dispersion value

10.92

Notes
[88] - 2-sided p-value; alpha=0.10.

Tofacitinib vs MTX at Month 3

Comparison groups

Tofacitinib (CP- 690,550) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.0596 ^[89]

Method

Normal approximation to the binomial

Parameter type

Mean difference (final values)

Point estimate

20.04

Confidence interval

level

90%

sides

2-sided

lower limit

2.53

upper limit

37.55

Variability estimate

Standard error of the mean

Dispersion value

10.64

Notes
[89] - 2-sided p-value; alpha=0.10.

Tofacitinib Plus MTX vs MTX at Month 6

Comparison groups

Tofacitinib (CP- 690,550) Plus Methotrexate (MTX) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.0017 ^[90]

Method

Normal approximation to the binomial

Parameter type

Mean difference (final values)

Point estimate

34.73

Confidence interval

level

90%

sides

2-sided

lower limit

16.51

upper limit

52.96

Variability estimate

Standard error of the mean

Dispersion value

11.07

Notes
[90] - 2-sided p-value; alpha=0.10.

Tofacitinib vs MTX at Month 6

Comparison groups

Tofacitinib (CP- 690,550) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.0097 ^[91]

Method

Normal approximation to the binomial

Parameter type

Mean difference (final values)

Point estimate

28.52

Confidence interval

level

90%

sides

2-sided

lower limit

10.36

upper limit

46.69

Variability estimate

Standard error of the mean

Dispersion value

11.04

Notes
[91] - 2-sided p-value; alpha=0.10.

Tofacitinib Plus MTX vs MTX at Month 9

Comparison groups

Tofacitinib (CP- 690,550) Plus Methotrexate (MTX) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.0016 ^[92]

Method

Normal approximation to the binomial

Parameter type

Mean difference (final values)

Point estimate

34.97

Confidence interval

level

90%

sides

2-sided

lower limit

16.68

upper limit

53.26

Variability estimate

Standard error of the mean

Dispersion value

11.11

Notes
[92] - 2-sided p-value; alpha=0.10.

Tofacitinib vs MTX at Month 9

Comparison groups

Tofacitinib (CP- 690,550) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.0102 ^[93]

Method

Normal approximation to the binomial

Parameter type

Mean difference (final values)

Point estimate

28.6

Confidence interval

level

90%

sides

2-sided

lower limit

10.28

upper limit

46.91

Variability estimate

Standard error of the mean

Dispersion value

11.13

Notes
[93] - 2-sided p-value; alpha=0.10.

Tofacitinib Plus MTX vs MTX at Month 12

Comparison groups

Tofacitinib (CP- 690,550) Plus Methotrexate (MTX) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.0017 ^[94]

Method

Normal approximation to the binomial

Parameter type

Mean difference (final values)

Point estimate

34.73

Confidence interval

level

90%

sides

2-sided

lower limit

16.51

upper limit

52.96

Variability estimate

Standard error of the mean

Dispersion value

11.07

Notes
[94] - 2-sided p-value; alpha=0.10.

Tofacitinib vs MTX at Month 12

Comparison groups

Tofacitinib (CP- 690,550) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.0381 ^[95]

Method

Normal approximation to the binomial

Parameter type

Mean difference (final values)

Point estimate

22.97

Confidence interval

level

90%

sides

2-sided

lower limit

4.74

upper limit

41.19

Variability estimate

Standard error of the mean

Dispersion value

11.07

Notes
[95] - 2-sided p-value; alpha=0.10

Secondary: Percentage of Subjects With DAS28-3 (CRP) Score <2.6

Top of page

End point title

Percentage of Subjects With DAS28-3 (CRP) Score <2.6

End point description

End point type

Secondary

End point timeframe

Month 1, 2, 3, 6, 9, 12

End point values	Tofacitinib (CP- 690,550) Plus Methotrexate (MTX)	Tofacitinib (CP- 690,550)	Methotrexate
Number of subjects analysed	34	36	37
Units: percentage of subjects
number (not applicable)
Month 1 (n=33,35,37)	18.18	5.71	5.41
Month 2 (n=34,36,37)	35.29	16.67	8.11
Month 3 (n=34,36,37)	32.35	22.22	13.51
Month 6 (n=34,36,37)	47.06	33.33	16.22
Month 9 (n=34,36,37)	50	38.89	18.92
Month 12 (n=34,36,37)	47.06	33.33	13.51

Tofacitinib Plus MTX vs MTX at Month 1

Comparison groups

Tofacitinib (CP- 690,550) Plus Methotrexate (MTX) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.0959 ^[96]

Method

Normal approximation to the binomial

Parameter type

Mean difference (final values)

Point estimate

12.77

Confidence interval

level

90%

sides

2-sided

lower limit

0.15

upper limit

25.4

Variability estimate

Standard error of the mean

Dispersion value

7.67

Notes
[96] - 2-sided p-value; alpha=0.10.

Tofacitinib vs MTX at Month 1

Comparison groups

Tofacitinib (CP- 690,550) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.9544 ^[97]

Method

Normal approximation to the binomial

Parameter type

Mean difference (final values)

Point estimate

0.3

Confidence interval

level

90%

sides

2-sided

lower limit

-8.58

upper limit

9.19

Variability estimate

Standard error of the mean

Dispersion value

5.4

Notes
[97] - 2-sided p-value; alpha=0.10.

Tofacitinib Plus MTX vs MTX at Month 2

Comparison groups

Tofacitinib (CP- 690,550) Plus Methotrexate (MTX) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.0036 ^[98]

Method

Normal approximation to the binomial

Parameter type

Mean difference (final values)

Point estimate

27.18

Confidence interval

level

90%

sides

2-sided

lower limit

11.81

upper limit

42.55

Variability estimate

Standard error of the mean

Dispersion value

9.34

Notes
[98] - 2-sided p-value; alpha=0.10.

Tofacitinib vs MTX at Month 2

Comparison groups

Tofacitinib (CP- 690,550) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.264 ^[99]

Method

Normal approximation to the binomial

Parameter type

Mean difference (final values)

Point estimate

8.55

Confidence interval

level

90%

sides

2-sided

lower limit

-4.04

upper limit

21.16

Variability estimate

Standard error of the mean

Dispersion value

7.66

Notes
[99] - 2-sided p-value; alpha=0.10.

Tofacitinib Plus MTX vs MTX at Month 3

Comparison groups

Tofacitinib (CP- 690,550) Plus Methotrexate (MTX) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.0544 ^[100]

Method

Normal approximation to the binomial

Parameter type

Mean difference (final values)

Point estimate

18.83

Confidence interval

level

90%

sides

2-sided

lower limit

2.72

upper limit

34.95

Variability estimate

Standard error of the mean

Dispersion value

9.79

Notes
[100] - 2-sided p-value; alpha=0.10.

Tofacitinib vs MTX at Month 3

Comparison groups

Tofacitinib (CP- 690,550) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.329 ^[101]

Method

Normal approximation to the binomial

Parameter type

Mean difference (final values)

Point estimate

8.7

Confidence interval

level

90%

sides

2-sided

lower limit

-5.96

upper limit

23.38

Variability estimate

Standard error of the mean

Dispersion value

8.92

Notes
[101] - 2-sided p-value; alpha=0.10.

Tofacitinib Plus MTX vs MTX at Month 6

Comparison groups

Tofacitinib (CP- 690,550) Plus Methotrexate (MTX) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.0032 ^[102]

Method

Normal approximation to the binomial

Parameter type

Mean difference (final values)

Point estimate

30.84

Confidence interval

level

90%

sides

2-sided

lower limit

13.59

upper limit

48.09

Variability estimate

Standard error of the mean

Dispersion value

10.48

Notes
[102] - 2-sided p-value; alpha=0.10.

Tofacitinib vs MTX at Month 6

Comparison groups

Tofacitinib (CP- 690,550) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.0845 ^[103]

Method

Normal approximation to the binomial

Parameter type

Mean difference (final values)

Point estimate

17.11

Confidence interval

level

90%

sides

2-sided

lower limit

0.79

upper limit

33.43

Variability estimate

Standard error of the mean

Dispersion value

9.92

Notes
[103] - 2-sided p-value; alpha=0.10.

Tofacitinib Plus MTX vs MTX at Month 9

Comparison groups

Tofacitinib (CP- 690,550) Plus Methotrexate (MTX) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.0037 ^[104]

Method

Normal approximation to the binomial

Parameter type

Mean difference (final values)

Point estimate

31.08

Confidence interval

level

90%

sides

2-sided

lower limit

13.44

upper limit

48.72

Variability estimate

Standard error of the mean

Dispersion value

10.72

Notes
[104] - 2-sided p-value; alpha=0.10.

Tofacitinib vs MTX at Month 9

Comparison groups

Tofacitinib (CP- 690,550) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.054 ^[105]

Method

Normal approximation to the binomial

Parameter type

Mean difference (final values)

Point estimate

19.96

Confidence interval

level

90%

sides

2-sided

lower limit

2.91

upper limit

37.02

Variability estimate

Standard error of the mean

Dispersion value

10.36

Notes
[105] - 2-sided p-value; alpha=0.10.

Tofacitinib Plus MTX vs MTX at Month 12

Comparison groups

Tofacitinib (CP- 690,550) Plus Methotrexate (MTX) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.001 ^[106]

Method

Normal approximation to the binomial

Parameter type

Mean difference (final values)

Point estimate

33.54

Confidence interval

level

90%

sides

2-sided

lower limit

16.7

upper limit

50.39

Variability estimate

Standard error of the mean

Dispersion value

10.24

Notes
[106] - 2-sided p-value; alpha=0.10.

Tofacitinib vs MTX at Month 12

Comparison groups

Tofacitinib (CP- 690,550) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.0401 ^[107]

Method

Normal approximation to the binomial

Parameter type

Mean difference (final values)

Point estimate

19.81

Confidence interval

level

90%

sides

2-sided

lower limit

3.92

upper limit

35.71

Variability estimate

Standard error of the mean

Dispersion value

9.66

Notes
[107] - 2-sided p-value; alpha=0.10.

Secondary: Percentage of Subjects With DAS28-4 (ESR) Response (Good or Moderate Improvement)

Top of page

End point title

Percentage of Subjects With DAS28-4 (ESR) Response (Good or Moderate Improvement)

End point description

DAS28-4(ESR) was calculated from swollen joint count and tender joint count using 28 joints count, ESR (mm/hour) and Subject's Global Assessment of Disease Activity (subject rated arthritis activity assessment). Total score range: 0 to 9.4, higher score=more disease activity. DAS28 categorical responses define a good (absolute: <3.2 or >1.2 improvement from BL), moderate (absolute: 3.2-5.1 or 0.6-1.2 change from BL), or no response (absolute: >5.1 or <0.6 change from BL). FAS NRI; n=number of subjects assessed for the specified parameter at a given visit.

End point type

Secondary

End point timeframe

Month 1, 2, 3, 6, 9, 12

End point values	Tofacitinib (CP- 690,550) Plus Methotrexate (MTX)	Tofacitinib (CP- 690,550)	Methotrexate
Number of subjects analysed	34	35	37
Units: percentage of subjects
number (not applicable)
Month 1 (n=34,35,37)	67.65	62.86	29.73
Month 2 (n=32,33,31)	85.29	69.44	59.46
Month 3 (n=33,33,31)	91.18	69.44	51.35
Month 6 (n=30,29,28)	85.29	77.78	51.35
Month 9 (n=30,28,24)	82.35	72.22	45.95
Month 12 (n=27,26,20)	79.41	69.44	45.95

Tofacitinib Plus MTX vs MTX at Month 1

Comparison groups

Tofacitinib (CP- 690,550) Plus Methotrexate (MTX) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.0005 ^[108]

Method

[Normal approximation to the binomial

Parameter type

Mean difference (final values)

Point estimate

37.91

Confidence interval

level

90%

sides

2-sided

lower limit

19.83

upper limit

55.99

Variability estimate

Standard error of the mean

Dispersion value

10.99

Notes
[108] - 2-sided p-value; alpha=0.10.

Tofacitinib vs MTX at Month 1

Comparison groups

Methotrexate v Tofacitinib (CP- 690,550)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.0028 ^[109]

Method

Normal approximation to the binomial

Parameter type

Mean difference (final values)

Point estimate

33.12

Confidence interval

level

90%

sides

2-sided

lower limit

14.87

upper limit

51.38

Variability estimate

Standard error of the mean

Dispersion value

11.09

Notes
[109] - 2-sided p-value; alpha=0.10.

Tofacitinib Plus MTX vs MTX at Month 2

Comparison groups

Tofacitinib (CP- 690,550) Plus Methotrexate (MTX) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.0105 ^[110]

Method

Normal approximation to the binomial

Parameter type

Mean difference (final values)

Point estimate

25.83

Confidence interval

level

90%

sides

2-sided

lower limit

9.21

upper limit

42.45

Variability estimate

Standard error of the mean

Dispersion value

10.1

Notes
[110] - 2-sided p-value; alpha=0.10.

Tofacitinib vs MTX at Month 2

Comparison groups

Tofacitinib (CP- 690,550) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.37 ^[111]

Method

Normal approximation to the binomial

Parameter type

Mean difference (final values)

Point estimate

9.98

Confidence interval

level

90%

sides

2-sided

lower limit

-8.33

upper limit

28.3

Variability estimate

Standard error of the mean

Dispersion value

11.13

Notes
[111] - 2-sided p-value; alpha=0.10.

Tofacitinib Plus MTX vs MTX at Month 3

Comparison groups

Tofacitinib (CP- 690,550) Plus Methotrexate (MTX) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.0001 ^[112]

Method

Normal approximation to the binomial

Parameter type

Mean difference (final values)

Point estimate

39.82

Confidence interval

level

90%

sides

2-sided

lower limit

24.11

upper limit

55.53

Variability estimate

Standard error of the mean

Dispersion value

9.54

Notes
[112] - 2-sided p-value; alpha=0.10.

Tofacitinib vs MTX at Month 3

Comparison groups

Tofacitinib (CP- 690,550) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.1076 ^[113]

Method

Normal approximation to the binomial

Parameter type

Mean difference (final values)

Point estimate

18.09

Confidence interval

level

90%

sides

2-sided

lower limit

-0.4

upper limit

36.59

Variability estimate

Standard error of the mean

Dispersion value

11.24

Notes
[113] - 2-sided p-value; alpha=0.10.

Tofacitinib Plus MTX vs MTX at Month 6

Comparison groups

Tofacitinib (CP- 690,550) Plus Methotrexate (MTX) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.0008 ^[114]

Method

Normal approximation to the binomial

Parameter type

Mean difference (final values)

Point estimate

33.94

Confidence interval

level

90%

sides

2-sided

lower limit

17.13

upper limit

50.75

Variability estimate

Standard error of the mean

Dispersion value

10.21

Notes
[114] - 2-sided p-value; alpha=0.10.

Tofacitinib vs MTX at Month 6

Comparison groups

Tofacitinib (CP- 690,550) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.0139 ^[115]

Method

Normal approximation to the binomial

Parameter type

Mean difference (final values)

Point estimate

26.42

Confidence interval

level

90%

sides

2-sided

lower limit

8.74

upper limit

44.1

Variability estimate

Standard error of the mean

Dispersion value

10.74

Notes
[115] - 2-sided p-value; alpha=0.10.

Tofacitinib Plus MTX vs MTX at Month 9

Comparison groups

Tofacitinib (CP- 690,550) Plus Methotrexate (MTX) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.0005 ^[116]

Method

Normal approximation to the binomial

Parameter type

Mean difference (final values)

Point estimate

36.4

Confidence interval

level

90%

sides

2-sided

lower limit

19.16

upper limit

53.64

Variability estimate

Standard error of the mean

Dispersion value

10.48

Notes
[116] - 2-sided p-value; alpha=0.10.

Tofacitinib vs MTX at Month 9

Comparison groups

Tofacitinib (CP- 690,550) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.0177

Method

Normal approximation to the binomial

Parameter type

Mean difference (final values)

Point estimate

26.27

Confidence interval

level

90%

sides

2-sided

lower limit

8.04

upper limit

44.5

Variability estimate

Standard error of the mean

Dispersion value

11.08

Tofacitinib Plus MTX vs MTX at Month 12

Comparison groups

Tofacitinib (CP- 690,550) Plus Methotrexate (MTX) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.0018 ^[117]

Method

Normal approximation to the binomial

Parameter type

Mean difference (final values)

Point estimate

33.46

Confidence interval

level

90%

sides

2-sided

lower limit

15.8

upper limit

51.12

Variability estimate

Standard error of the mean

Dispersion value

10.73

Notes
[117] - 2-sided p-value; alpha=0.10.

Tofacitinib vs MTX at Month 12

Comparison groups

Tofacitinib (CP- 690,550) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.0363 ^[118]

Method

Normal approximation to the binomial

Parameter type

Mean difference (final values)

Point estimate

23.49

Confidence interval

level

90%

sides

2-sided

lower limit

5.02

upper limit

41.96

Variability estimate

Standard error of the mean

Dispersion value

11.22

Notes
[118] - 2-sided p-value; alpha=0.10.

Secondary: Percentage of Subjects With DAS28-4 (ESR) <=3.2

Top of page

End point title

Percentage of Subjects With DAS28-4 (ESR) <=3.2

End point description

DAS28-4(ESR) was calculated from swollen joint count and tender joint count using 28 joints count, ESR (mm/hour) and Subject's Global Assessment of Disease Activity (subject rated arthritis activity assessment). Total score range: 0 to 9.4, higher score=more disease activity. DAS28-4(ESR) <=3.2 implied low disease activity. FAS NRI; n=number of subjects assessed for the specified parameter at a given visit.

End point type

Secondary

End point timeframe

Month 1, 2, 3, 6, 9, 12

End point values	Tofacitinib (CP- 690,550) Plus Methotrexate (MTX)	Tofacitinib (CP- 690,550)	Methotrexate
Number of subjects analysed	34	36	37
Units: percentage of subjects
number (not applicable)
Month 1 (n=34,35,37)	20.59	8.57	2.7
Month 2 (n=34,36,37)	35.29	13.89	8.11
Month 3 (n=34,36,37)	32.35	30.56	13.51
Month 6 (n=34,36,37)	41.18	27.78	18.92
Month 9 (n=34,36,37)	44.12	33.33	18.92
Month 12 (n=34,36,37)	50	30.56	16.22

Tofacitinib Plus MTX vs MTX at Month 1

Comparison groups

Tofacitinib (CP- 690,550) Plus Methotrexate (MTX) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.016 ^[119]

Method

Normal approximation to the binomial

Parameter type

Mean difference (final values)

Point estimate

17.88

Confidence interval

level

90%

sides

2-sided

lower limit

5.66

upper limit

30.1

Variability estimate

Standard error of the mean

Dispersion value

7.42

Notes
[119] - 2-sided p-value; alpha=0.10.

Tofacitinib vs MTX at Month 1

Comparison groups

Tofacitinib (CP- 690,550) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.2798 ^[120]

Method

Normal approximation to the binomial

Parameter type

Mean difference (final values)

Point estimate

5.86

Confidence interval

level

90%

sides

2-sided

lower limit

-3.06

upper limit

14.8

Variability estimate

Standard error of the mean

Dispersion value

5.43

Notes
[120] - 2-sided p-value; alpha=0.10.

Tofacitinib Plus MTX vs MTX at Month 2

Comparison groups

Tofacitinib (CP- 690,550) Plus Methotrexate (MTX) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.0036 ^[121]

Method

Normal approximation to the binomial

Parameter type

Mean difference (final values)

Point estimate

27.18

Confidence interval

level

90%

sides

2-sided

lower limit

11.81

upper limit

42.55

Variability estimate

Standard error of the mean

Dispersion value

9.34

Notes
[121] - 2-sided p-value; alpha=0.10

Tofacitinib vs MTX at Month 2

Comparison groups

Tofacitinib (CP- 690,550) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.4287 ^[122]

Method

Normal approximation to the binomial

Parameter type

Mean difference (final values)

Point estimate

5.78

Confidence interval

level

90%

sides

2-sided

lower limit

-6.23

upper limit

17.79

Variability estimate

Standard error of the mean

Dispersion value

7.3

Notes
[122] - 2-sided p-value; alpha=0.10.

Tofacitinib Plus MTX vs MTX at Month 3

Comparison groups

Methotrexate v Tofacitinib (CP- 690,550) Plus Methotrexate (MTX)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.0544 ^[123]

Method

Normal approximation to the binomial

Parameter type

Mean difference (final values)

Point estimate

18.83

Confidence interval

level

90%

sides

2-sided

lower limit

2.72

upper limit

34.95

Variability estimate

Standard error of the mean

Dispersion value

9.79

Notes
[123] - 2-sided p-value; alpha=0.10.

Tofacitinib vs MTX at Month 3

Comparison groups

Tofacitinib (CP- 690,550) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.0732 ^[124]

Method

Normal approximation to the binomial

Parameter type

Mean difference (final values)

Point estimate

17.04

Confidence interval

level

90%

sides

2-sided

lower limit

1.39

upper limit

32.69

Variability estimate

Standard error of the mean

Dispersion value

9.51

Notes
[124] - 2-sided p-value; alpha=0.10

Tofacitinib Plus MTX vs MTX at Month 6

Comparison groups

Tofacitinib (CP- 690,550) Plus Methotrexate (MTX) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.036 ^[125]

Method

Normal approximation to the binomial

Parameter type

Mean difference (final values)

Point estimate

22.25

Confidence interval

level

90%

sides

2-sided

lower limit

4.79

upper limit

39.72

Variability estimate

Standard error of the mean

Dispersion value

10.61

Notes
[125] - 2-sided p-value; alpha=0.10.

Tofacitinib vs MTX at Month 6

Comparison groups

Tofacitinib (CP- 690,550) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.3688 ^[126]

Method

Normal approximation to the binomial

Parameter type

Mean difference (final values)

Point estimate

8.85

Confidence interval

level

90%

sides

2-sided

lower limit

-7.35

upper limit

25.07

Variability estimate

Standard error of the mean

Dispersion value

9.85

Notes
[126] - 2-sided p-value; alpha=0.10.

Tofacitinib Plus MTX vs MTX at Month 9

Comparison groups

Tofacitinib (CP- 690,550) Plus Methotrexate (MTX) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.0182 ^[127]

Method

Normal approximation to the binomial

Parameter type

Mean difference (final values)

Point estimate

25.19

Confidence interval

level

90%

sides

2-sided

lower limit

7.63

upper limit

42.76

Variability estimate

Standard error of the mean

Dispersion value

10.67

Notes
[127] - 2-sided p-value; alpha=0.10.

Tofacitinib vs MTX at Month 9

Comparison groups

Tofacitinib (CP- 690,550) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.1558 ^[128]

Method

Normal approximation to the binomial

Parameter type

Mean difference (final values)

Point estimate

14.41

Confidence interval

level

90%

sides

2-sided

lower limit

-2.29

upper limit

31.12

Variability estimate

Standard error of the mean

Dispersion value

10.15

Notes
[128] - 2-sided p-value; alpha=0.10.

Tofacitinib Plus MTX vs MTX at Month 12

Comparison groups

Tofacitinib (CP- 690,550) Plus Methotrexate (MTX) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.0012 ^[129]

Method

Normal approximation to the binomial

Parameter type

Mean difference (final values)

Point estimate

33.78

Confidence interval

level

90%

sides

2-sided

lower limit

16.51

upper limit

51.05

Variability estimate

Standard error of the mean

Dispersion value

10.49

Notes
[129] - 2-sided p-value; alpha=0.10.

Tofacitinib vs MTX at Month 12

Comparison groups

Tofacitinib (CP- 690,550) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.1426 ^[130]

Method

Normal approximation to the binomial

Parameter type

Mean difference (net)

Point estimate

14.33

Confidence interval

level

90%

sides

2-sided

lower limit

-1.74

upper limit

30.42

Variability estimate

Standard error of the mean

Dispersion value

9.78

Notes
[130] - 2-sided p-value; alpha=0.10

Secondary: Percentage of Subjects With DAS28-4 (ESR) <2.6

Top of page

End point title

Percentage of Subjects With DAS28-4 (ESR) <2.6

End point description

DAS28-4(ESR) was calculated from swollen joint count and tender joint count using 28 joints count, ESR (mm/hour) and Subject's Global Assessment of Disease Activity (subject rated arthritis activity assessment). Total score range: 0 to 9.4, higher score=more disease activity. DAS28-4(ESR) <2.6 implied remission. FAS NRI; n=number of subjects assessed for the specified parameter at a given visit.

End point type

Secondary

End point timeframe

Month 1, 2, 3, 6, 9, 12

End point values	Tofacitinib (CP- 690,550) Plus Methotrexate (MTX)	Tofacitinib (CP- 690,550)	Methotrexate
Number of subjects analysed	34	36	37
Units: percentage of subjects
number (not applicable)
Month 1 (n=34,35,37)	5.88	2.86	0
Month 2 (n=34,36,37)	17.65	5.56	2.7
Month 3 (n=34,36,37)	23.53	2.78	13.51
Month 6 (n=34,36,37)	29.41	13.89	13.51
Month 9 (n=34,36,37)	35.29	13.89	16.22
Month 12 (n=34,36,37)	32.35	19.44	13.51

Tofacitinib Plus MTX vs MTX at Month 1

Comparison groups

Tofacitinib (CP- 690,550) Plus Methotrexate (MTX) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.1449 ^[131]

Method

Normal approximation to the binomial

Parameter type

Mean difference (final values)

Point estimate

5.88

Confidence interval

level

90%

sides

2-sided

lower limit

-0.75

upper limit

12.52

Variability estimate

Standard error of the mean

Dispersion value

4.03

Notes
[131] - 2-sided p-value; alpha=0.10.

Tofacitinib vs MTX at Month 1

Comparison groups

Tofacitinib (CP- 690,550) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.3102 ^[132]

Method

Normal approximation to the binomial

Parameter type

Mean difference (final values)

Point estimate

2.85

Confidence interval

level

90%

sides

2-sided

lower limit

-1.77

upper limit

7.48

Variability estimate

Standard error of the mean

Dispersion value

2.81

Notes
[132] - 2-sided p-value; alpha=0.10.

Tofacitinib Plus MTX vs MTX at Month 2

Comparison groups

Tofacitinib (CP- 690,550) Plus Methotrexate (MTX) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.0342 ^[133]

Method

Normal approximation to the binomial

Parameter type

Mean difference (final values)

Point estimate

14.94

Confidence interval

level

90%

sides

2-sided

lower limit

3.32

upper limit

26.55

Variability estimate

Standard error of the mean

Dispersion value

7.06

Notes
[133] - 2-sided p-value; alpha=0.10.

Tofacitinib vs MTX at Month 2

Comparison groups

Tofacitinib (CP- 690,550) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.54 ^[134]

Method

Normal approximation to the binomial

Parameter type

Mean difference (final values)

Point estimate

2.85

Confidence interval

level

90%

sides

2-sided

lower limit

-4.8

upper limit

10.51

Variability estimate

Standard error of the mean

Dispersion value

4.65

Notes
[134] - 2-sided p-value; alpha=0.10.

Tofacitinib Plus MTX vs MTX at Month 3

Comparison groups

Tofacitinib (CP- 690,550) Plus Methotrexate (MTX) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.2759 ^[135]

Method

Normal approximation to the binomial

Parameter type

Mean difference (final values)

Point estimate

10.01

Confidence interval

level

90%

sides

2-sided

lower limit

-5.1

upper limit

25.13

Variability estimate

Standard error of the mean

Dispersion value

9.19

Notes
[135] - 2-sided p-value; alpha=0.10.

Tofacitinib vs MTX at Month 3

Comparison groups

Tofacitinib (CP- 690,550) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.0859 ^[136]

Method

Normal approximation to the binomial

Parameter type

Mean difference (final values)

Point estimate

-10.73

Confidence interval

level

90%

sides

2-sided

lower limit

-21.02

upper limit

-0.45

Variability estimate

Standard error of the mean

Dispersion value

6.25

Notes
[136] - 2-sided p-value; alpha=0.10.

Tofacitinib Plus MTX vs MTX at Month 6

Comparison groups

Tofacitinib (CP- 690,550) Plus Methotrexate (MTX) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.0985 ^[137]

Method

Normal approximation to the binomial

Parameter type

Mean difference (final values)

Point estimate

15.89

Confidence interval

level

90%

sides

2-sided

lower limit

0.06

upper limit

31.73

Variability estimate

Standard error of the mean

Dispersion value

9.62

Notes
[137] - 2-sided p-value; alpha=0.10.

Tofacitinib vs MTX at Month 6

Comparison groups

Tofacitinib (CP- 690,550) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.9628 ^[138]

Method

Normal approximation to the binomial

Parameter type

Mean difference (final values)

Point estimate

0.37

Confidence interval

level

90%

sides

2-sided

lower limit

-12.86

upper limit

13.61

Variability estimate

Standard error of the mean

Dispersion value

8.05

Notes
[138] - 2-sided p-value; alpha=0.10.

Tofacitinib Plus MTX vs MTX at Month 9

Comparison groups

Methotrexate v Tofacitinib (CP- 690,550) Plus Methotrexate (MTX)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.0612 ^[139]

Method

Normal approximation to the binomial

Parameter type

Mean difference (final values)

Point estimate

19.07

Confidence interval

level

90%

sides

2-sided

lower limit

2.31

upper limit

35.84

Variability estimate

Standard error of the mean

Dispersion value

10.19

Notes
[139] - 2-sided p-value; alpha=0.10.

Tofacitinib vs MTX at Month 9

Comparison groups

Tofacitinib (CP- 690,550) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.7807 ^[140]

Method

Normal approximation to

Parameter type

Mean difference (final values)

Point estimate

-2.32

Confidence interval

level

90%

sides

2-sided

lower limit

-16.08

upper limit

11.43

Variability estimate

Standard error of the mean

Dispersion value

8.36

Notes
[140] - 2-sided p-value; alpha=0.10.

Tofacitinib Plus MTX vs MTX at Month 12

Comparison groups

Tofacitinib (CP- 690,550) Plus Methotrexate (MTX) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.0544 ^[141]

Method

Normal approximation to the binomial

Parameter type

Mean difference (final values)

Point estimate

18.83

Confidence interval

level

90%

sides

2-sided

lower limit

2.72

upper limit

34.95

Variability estimate

Standard error of the mean

Dispersion value

9.79

Notes
[141] - 2-sided p-value; alpha=0.10.

Tofacitinib vs MTX at Month 12

Comparison groups

Tofacitinib (CP- 690,550) v Methotrexate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.4937 ^[142]

Method

Normal approximation to the binomial

Parameter type

Mean difference (final values)

Point estimate

5.93

Confidence interval

level

90%

sides

2-sided

lower limit

-8.32

upper limit

20.18

Variability estimate

Standard error of the mean

Dispersion value

8.66

Notes
[142] - 2-sided p-value; alpha=0.10.

Adverse events

Top of page

Timeframe for reporting adverse events

Adverse events were collected up to 28 calendar days after the last administration of investigational product.

Adverse event reporting additional description

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

Assessment type

Non-systematic

Dictionary name

MedDRA

Dictionary version

16.1

Reporting group title

Tofacitinib (CP- 690,550) Plus Methotrexate (MTX)

Reporting group description

Reporting group title

Tofacitinib (CP- 690,550)

Reporting group description

Reporting group title

Methotrexate

Reporting group description

Subjects received MTX capsules and matching placebo CP-690,550 tablets. Subjects also received folate supplementation according to local MTX label guidelines and standard of care.

Serious adverse events	Tofacitinib (CP- 690,550) Plus Methotrexate (MTX)	Tofacitinib (CP- 690,550)	Methotrexate
Total subjects affected by serious adverse events
subjects affected / exposed	2 / 36 (5.56%)	1 / 36 (2.78%)	2 / 37 (5.41%)
number of deaths (all causes)	0	0	0
number of deaths resulting from adverse events
Cardiac disorders
Angina pectoris
subjects affected / exposed	0 / 36 (0.00%)	1 / 36 (2.78%)	0 / 37 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Haematochezia
subjects affected / exposed	0 / 36 (0.00%)	0 / 36 (0.00%)	1 / 37 (2.70%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Hepatobiliary disorders
Cholelithiasis
subjects affected / exposed	0 / 36 (0.00%)	0 / 36 (0.00%)	1 / 37 (2.70%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Foot deformity
subjects affected / exposed	1 / 36 (2.78%)	0 / 36 (0.00%)	0 / 37 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Infections and infestations
Anal abscess
subjects affected / exposed	1 / 36 (2.78%)	0 / 36 (0.00%)	0 / 37 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0

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

Non-serious adverse events	Tofacitinib (CP- 690,550) Plus Methotrexate (MTX)	Tofacitinib (CP- 690,550)	Methotrexate
Total subjects affected by non serious adverse events
subjects affected / exposed	24 / 36 (66.67%)	31 / 36 (86.11%)	29 / 37 (78.38%)
Vascular disorders
Hypertension
subjects affected / exposed	1 / 36 (2.78%)	6 / 36 (16.67%)	0 / 37 (0.00%)
occurrences all number	1	6	0
General disorders and administration site conditions
Chest pain
subjects affected / exposed	1 / 36 (2.78%)	0 / 36 (0.00%)	0 / 37 (0.00%)
occurrences all number	1	0	0
Local swelling
subjects affected / exposed	1 / 36 (2.78%)	0 / 36 (0.00%)	0 / 37 (0.00%)
occurrences all number	1	0	0
Malaise
subjects affected / exposed	1 / 36 (2.78%)	0 / 36 (0.00%)	0 / 37 (0.00%)
occurrences all number	1	0	0
Non-cardiac chest pain
subjects affected / exposed	0 / 36 (0.00%)	1 / 36 (2.78%)	0 / 37 (0.00%)
occurrences all number	0	1	0
Pyrexia
subjects affected / exposed	0 / 36 (0.00%)	1 / 36 (2.78%)	0 / 37 (0.00%)
occurrences all number	0	1	0
Reproductive system and breast disorders
Breast tenderness
subjects affected / exposed	1 / 36 (2.78%)	0 / 36 (0.00%)	0 / 37 (0.00%)
occurrences all number	1	0	0
Menorrhagia
subjects affected / exposed	0 / 36 (0.00%)	2 / 36 (5.56%)	0 / 37 (0.00%)
occurrences all number	0	2	0
Sexual dysfunction
subjects affected / exposed	0 / 36 (0.00%)	0 / 36 (0.00%)	1 / 37 (2.70%)
occurrences all number	0	0	1
Uterine fibrosis
subjects affected / exposed	1 / 36 (2.78%)	0 / 36 (0.00%)	0 / 37 (0.00%)
occurrences all number	1	0	0
Vaginal discharge
subjects affected / exposed	0 / 36 (0.00%)	0 / 36 (0.00%)	1 / 37 (2.70%)
occurrences all number	0	0	1
Respiratory, thoracic and mediastinal disorders
Cough
subjects affected / exposed	1 / 36 (2.78%)	0 / 36 (0.00%)	1 / 37 (2.70%)
occurrences all number	1	0	1
Epistaxis
subjects affected / exposed	0 / 36 (0.00%)	1 / 36 (2.78%)	0 / 37 (0.00%)
occurrences all number	0	1	0
Nasal congestion
subjects affected / exposed	0 / 36 (0.00%)	0 / 36 (0.00%)	1 / 37 (2.70%)
occurrences all number	0	0	1
Oropharyngeal pain
subjects affected / exposed	1 / 36 (2.78%)	1 / 36 (2.78%)	0 / 37 (0.00%)
occurrences all number	1	3	0
Pharyngeal inflammation
subjects affected / exposed	0 / 36 (0.00%)	0 / 36 (0.00%)	1 / 37 (2.70%)
occurrences all number	0	0	1
Rhinitis allergic
subjects affected / exposed	0 / 36 (0.00%)	0 / 36 (0.00%)	1 / 37 (2.70%)
occurrences all number	0	0	1
Upper respiratory tract inflammation
subjects affected / exposed	0 / 36 (0.00%)	1 / 36 (2.78%)	0 / 37 (0.00%)
occurrences all number	0	1	0
Psychiatric disorders
Depression
subjects affected / exposed	1 / 36 (2.78%)	0 / 36 (0.00%)	0 / 37 (0.00%)
occurrences all number	1	0	0
Insomnia
subjects affected / exposed	1 / 36 (2.78%)	1 / 36 (2.78%)	0 / 37 (0.00%)
occurrences all number	1	1	0
Investigations
Alanine aminotransferase increased
subjects affected / exposed	6 / 36 (16.67%)	0 / 36 (0.00%)	5 / 37 (13.51%)
occurrences all number	7	0	8
Aspartate aminotransferase increased
subjects affected / exposed	2 / 36 (5.56%)	1 / 36 (2.78%)	3 / 37 (8.11%)
occurrences all number	2	1	3
Blood bicarbonate decreased
subjects affected / exposed	1 / 36 (2.78%)	0 / 36 (0.00%)	0 / 37 (0.00%)
occurrences all number	1	0	0
Blood cholesterol increased
subjects affected / exposed	0 / 36 (0.00%)	1 / 36 (2.78%)	0 / 37 (0.00%)
occurrences all number	0	1	0
Blood creatine phosphokinase increased
subjects affected / exposed	1 / 36 (2.78%)	3 / 36 (8.33%)	1 / 37 (2.70%)
occurrences all number	1	4	1
Blood glucose increased
subjects affected / exposed	1 / 36 (2.78%)	0 / 36 (0.00%)	0 / 37 (0.00%)
occurrences all number	1	0	0
Gamma-glutamyltransferase increased
subjects affected / exposed	1 / 36 (2.78%)	0 / 36 (0.00%)	2 / 37 (5.41%)
occurrences all number	1	0	3
Haemoglobin decreased
subjects affected / exposed	0 / 36 (0.00%)	0 / 36 (0.00%)	1 / 37 (2.70%)
occurrences all number	0	0	1
Hepatic enzyme increased
subjects affected / exposed	2 / 36 (5.56%)	1 / 36 (2.78%)	2 / 37 (5.41%)
occurrences all number	4	1	2
Liver function test abnormal
subjects affected / exposed	0 / 36 (0.00%)	0 / 36 (0.00%)	1 / 37 (2.70%)
occurrences all number	0	0	1
Red blood cell count decreased
subjects affected / exposed	1 / 36 (2.78%)	0 / 36 (0.00%)	0 / 37 (0.00%)
occurrences all number	1	0	0
Transaminases increased
subjects affected / exposed	2 / 36 (5.56%)	0 / 36 (0.00%)	0 / 37 (0.00%)
occurrences all number	2	0	0
Weight increased
subjects affected / exposed	0 / 36 (0.00%)	2 / 36 (5.56%)	0 / 37 (0.00%)
occurrences all number	0	2	0
Injury, poisoning and procedural complications
Toxicity to various agents
subjects affected / exposed	1 / 36 (2.78%)	0 / 36 (0.00%)	0 / 37 (0.00%)
occurrences all number	1	0	0
Cardiac disorders
Angina pectoris
subjects affected / exposed	0 / 36 (0.00%)	1 / 36 (2.78%)	0 / 37 (0.00%)
occurrences all number	0	1	0
Myocardial ischaemia
subjects affected / exposed	0 / 36 (0.00%)	1 / 36 (2.78%)	0 / 37 (0.00%)
occurrences all number	0	1	0
Palpitations
subjects affected / exposed	0 / 36 (0.00%)	1 / 36 (2.78%)	1 / 37 (2.70%)
occurrences all number	0	1	1
Nervous system disorders
Dizziness
subjects affected / exposed	1 / 36 (2.78%)	1 / 36 (2.78%)	0 / 37 (0.00%)
occurrences all number	1	1	0
Headache
subjects affected / exposed	3 / 36 (8.33%)	2 / 36 (5.56%)	2 / 37 (5.41%)
occurrences all number	4	2	2
Hypoaesthesia
subjects affected / exposed	1 / 36 (2.78%)	0 / 36 (0.00%)	0 / 37 (0.00%)
occurrences all number	1	0	0
Sciatica
subjects affected / exposed	1 / 36 (2.78%)	0 / 36 (0.00%)	0 / 37 (0.00%)
occurrences all number	1	0	0
Tension headache
subjects affected / exposed	0 / 36 (0.00%)	0 / 36 (0.00%)	1 / 37 (2.70%)
occurrences all number	0	0	1
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	1 / 36 (2.78%)	0 / 36 (0.00%)	1 / 37 (2.70%)
occurrences all number	1	0	1
Leukopenia
subjects affected / exposed	1 / 36 (2.78%)	1 / 36 (2.78%)	1 / 37 (2.70%)
occurrences all number	1	1	1
Lymph node pain
subjects affected / exposed	0 / 36 (0.00%)	1 / 36 (2.78%)	0 / 37 (0.00%)
occurrences all number	0	2	0
Lymphadenopathy
subjects affected / exposed	0 / 36 (0.00%)	1 / 36 (2.78%)	0 / 37 (0.00%)
occurrences all number	0	1	0
Lymphopenia
subjects affected / exposed	1 / 36 (2.78%)	1 / 36 (2.78%)	1 / 37 (2.70%)
occurrences all number	1	1	1
Macrocytosis
subjects affected / exposed	1 / 36 (2.78%)	0 / 36 (0.00%)	0 / 37 (0.00%)
occurrences all number	1	0	0
Neutropenia
subjects affected / exposed	0 / 36 (0.00%)	1 / 36 (2.78%)	0 / 37 (0.00%)
occurrences all number	0	1	0
Neutrophilia
subjects affected / exposed	0 / 36 (0.00%)	1 / 36 (2.78%)	0 / 37 (0.00%)
occurrences all number	0	1	0
Normochromic normocytic anaemia
subjects affected / exposed	0 / 36 (0.00%)	0 / 36 (0.00%)	1 / 37 (2.70%)
occurrences all number	0	0	1
Thrombocytosis
subjects affected / exposed	0 / 36 (0.00%)	1 / 36 (2.78%)	0 / 37 (0.00%)
occurrences all number	0	1	0
Ear and labyrinth disorders
Ear pruritus
subjects affected / exposed	0 / 36 (0.00%)	1 / 36 (2.78%)	0 / 37 (0.00%)
occurrences all number	0	1	0
Vertigo
subjects affected / exposed	0 / 36 (0.00%)	0 / 36 (0.00%)	1 / 37 (2.70%)
occurrences all number	0	0	2
Eye disorders
Eye disorder
subjects affected / exposed	0 / 36 (0.00%)	0 / 36 (0.00%)	1 / 37 (2.70%)
occurrences all number	0	0	1
Lacrimation increased
subjects affected / exposed	1 / 36 (2.78%)	0 / 36 (0.00%)	0 / 37 (0.00%)
occurrences all number	1	0	0
Scleritis
subjects affected / exposed	0 / 36 (0.00%)	0 / 36 (0.00%)	1 / 37 (2.70%)
occurrences all number	0	0	1
Visual acuity reduced
subjects affected / exposed	0 / 36 (0.00%)	0 / 36 (0.00%)	1 / 37 (2.70%)
occurrences all number	0	0	1
Xerophthalmia
subjects affected / exposed	1 / 36 (2.78%)	0 / 36 (0.00%)	0 / 37 (0.00%)
occurrences all number	1	0	0
Gastrointestinal disorders
Abdominal distension
subjects affected / exposed	0 / 36 (0.00%)	1 / 36 (2.78%)	0 / 37 (0.00%)
occurrences all number	0	1	0
Abdominal pain
subjects affected / exposed	1 / 36 (2.78%)	0 / 36 (0.00%)	1 / 37 (2.70%)
occurrences all number	1	0	1
Abdominal pain lower
subjects affected / exposed	0 / 36 (0.00%)	1 / 36 (2.78%)	0 / 37 (0.00%)
occurrences all number	0	1	0
Abdominal pain upper
subjects affected / exposed	2 / 36 (5.56%)	1 / 36 (2.78%)	2 / 37 (5.41%)
occurrences all number	3	1	2
Abdominal tenderness
subjects affected / exposed	1 / 36 (2.78%)	0 / 36 (0.00%)	0 / 37 (0.00%)
occurrences all number	1	0	0
Aphthous stomatitis
subjects affected / exposed	0 / 36 (0.00%)	0 / 36 (0.00%)	1 / 37 (2.70%)
occurrences all number	0	0	1
Constipation
subjects affected / exposed	0 / 36 (0.00%)	1 / 36 (2.78%)	0 / 37 (0.00%)
occurrences all number	0	1	0
Diarrhoea
subjects affected / exposed	1 / 36 (2.78%)	2 / 36 (5.56%)	1 / 37 (2.70%)
occurrences all number	1	2	1
Dry mouth
subjects affected / exposed	2 / 36 (5.56%)	0 / 36 (0.00%)	0 / 37 (0.00%)
occurrences all number	2	0	0
Dyspepsia
subjects affected / exposed	2 / 36 (5.56%)	1 / 36 (2.78%)	1 / 37 (2.70%)
occurrences all number	2	1	1
Food poisoning
subjects affected / exposed	0 / 36 (0.00%)	1 / 36 (2.78%)	0 / 37 (0.00%)
occurrences all number	0	1	0
Gastric disorder
subjects affected / exposed	0 / 36 (0.00%)	1 / 36 (2.78%)	0 / 37 (0.00%)
occurrences all number	0	1	0
Gastritis
subjects affected / exposed	0 / 36 (0.00%)	5 / 36 (13.89%)	4 / 37 (10.81%)
occurrences all number	0	6	4
Gastrooesophageal reflux disease
subjects affected / exposed	0 / 36 (0.00%)	1 / 36 (2.78%)	0 / 37 (0.00%)
occurrences all number	0	1	0
Hyperchlorhydria
subjects affected / exposed	1 / 36 (2.78%)	0 / 36 (0.00%)	0 / 37 (0.00%)
occurrences all number	2	0	0
Irritable bowel syndrome
subjects affected / exposed	1 / 36 (2.78%)	1 / 36 (2.78%)	0 / 37 (0.00%)
occurrences all number	1	1	0
Nausea
subjects affected / exposed	0 / 36 (0.00%)	1 / 36 (2.78%)	1 / 37 (2.70%)
occurrences all number	0	1	1
Stomatitis
subjects affected / exposed	1 / 36 (2.78%)	0 / 36 (0.00%)	0 / 37 (0.00%)
occurrences all number	1	0	0
Hepatobiliary disorders
Cholelithiasis
subjects affected / exposed	0 / 36 (0.00%)	0 / 36 (0.00%)	1 / 37 (2.70%)
occurrences all number	0	0	2
Hepatic steatosis
subjects affected / exposed	1 / 36 (2.78%)	0 / 36 (0.00%)	0 / 37 (0.00%)
occurrences all number	1	0	0
Hypertransaminasaemia
subjects affected / exposed	2 / 36 (5.56%)	1 / 36 (2.78%)	2 / 37 (5.41%)
occurrences all number	3	1	2
Skin and subcutaneous tissue disorders
Acne
subjects affected / exposed	0 / 36 (0.00%)	1 / 36 (2.78%)	0 / 37 (0.00%)
occurrences all number	0	1	0
Alopecia
subjects affected / exposed	3 / 36 (8.33%)	0 / 36 (0.00%)	3 / 37 (8.11%)
occurrences all number	3	0	3
Diffuse alopecia
subjects affected / exposed	0 / 36 (0.00%)	0 / 36 (0.00%)	1 / 37 (2.70%)
occurrences all number	0	0	1
Ecchymosis
subjects affected / exposed	0 / 36 (0.00%)	1 / 36 (2.78%)	0 / 37 (0.00%)
occurrences all number	0	1	0
Ingrowing nail
subjects affected / exposed	0 / 36 (0.00%)	1 / 36 (2.78%)	0 / 37 (0.00%)
occurrences all number	0	1	0
Night sweats
subjects affected / exposed	0 / 36 (0.00%)	0 / 36 (0.00%)	1 / 37 (2.70%)
occurrences all number	0	0	1
Pruritus
subjects affected / exposed	1 / 36 (2.78%)	0 / 36 (0.00%)	0 / 37 (0.00%)
occurrences all number	1	0	0
Rash
subjects affected / exposed	1 / 36 (2.78%)	4 / 36 (11.11%)	0 / 37 (0.00%)
occurrences all number	1	4	0
Rosacea
subjects affected / exposed	0 / 36 (0.00%)	1 / 36 (2.78%)	0 / 37 (0.00%)
occurrences all number	0	1	0
Renal and urinary disorders
Dysuria
subjects affected / exposed	1 / 36 (2.78%)	0 / 36 (0.00%)	0 / 37 (0.00%)
occurrences all number	1	0	0
Urinary incontinence
subjects affected / exposed	0 / 36 (0.00%)	1 / 36 (2.78%)	0 / 37 (0.00%)
occurrences all number	0	1	0
Endocrine disorders
Hypothyroidism
subjects affected / exposed	0 / 36 (0.00%)	1 / 36 (2.78%)	0 / 37 (0.00%)
occurrences all number	0	1	0
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	1 / 36 (2.78%)	1 / 36 (2.78%)	0 / 37 (0.00%)
occurrences all number	4	1	0
Back pain
subjects affected / exposed	1 / 36 (2.78%)	0 / 36 (0.00%)	2 / 37 (5.41%)
occurrences all number	1	0	2
Joint swelling
subjects affected / exposed	1 / 36 (2.78%)	0 / 36 (0.00%)	0 / 37 (0.00%)
occurrences all number	1	0	0
Musculoskeletal stiffness
subjects affected / exposed	1 / 36 (2.78%)	0 / 36 (0.00%)	0 / 37 (0.00%)
occurrences all number	1	0	0
Myalgia
subjects affected / exposed	1 / 36 (2.78%)	0 / 36 (0.00%)	0 / 37 (0.00%)
occurrences all number	1	0	0
Pain in extremity
subjects affected / exposed	0 / 36 (0.00%)	1 / 36 (2.78%)	0 / 37 (0.00%)
occurrences all number	0	1	0
Rheumatoid arthritis
subjects affected / exposed	0 / 36 (0.00%)	2 / 36 (5.56%)	5 / 37 (13.51%)
occurrences all number	0	2	5
Rheumatoid nodule
subjects affected / exposed	0 / 36 (0.00%)	1 / 36 (2.78%)	0 / 37 (0.00%)
occurrences all number	0	1	0
Tendonitis
subjects affected / exposed	0 / 36 (0.00%)	1 / 36 (2.78%)	0 / 37 (0.00%)
occurrences all number	0	1	0
Infections and infestations
Acute tonsillitis
subjects affected / exposed	0 / 36 (0.00%)	0 / 36 (0.00%)	1 / 37 (2.70%)
occurrences all number	0	0	1
Anal abscess
subjects affected / exposed	1 / 36 (2.78%)	0 / 36 (0.00%)	0 / 37 (0.00%)
occurrences all number	2	0	0
Bronchitis
subjects affected / exposed	3 / 36 (8.33%)	0 / 36 (0.00%)	0 / 37 (0.00%)
occurrences all number	3	0	0
Folliculitis
subjects affected / exposed	0 / 36 (0.00%)	1 / 36 (2.78%)	0 / 37 (0.00%)
occurrences all number	0	1	0
Fungal skin infection
subjects affected / exposed	1 / 36 (2.78%)	0 / 36 (0.00%)	0 / 37 (0.00%)
occurrences all number	1	0	0
Furuncle
subjects affected / exposed	0 / 36 (0.00%)	1 / 36 (2.78%)	0 / 37 (0.00%)
occurrences all number	0	1	0
Gastroenteritis
subjects affected / exposed	2 / 36 (5.56%)	0 / 36 (0.00%)	0 / 37 (0.00%)
occurrences all number	2	0	0
Influenza
subjects affected / exposed	2 / 36 (5.56%)	2 / 36 (5.56%)	0 / 37 (0.00%)
occurrences all number	1	2	0
Nasopharyngitis
subjects affected / exposed	1 / 36 (2.78%)	0 / 36 (0.00%)	1 / 37 (2.70%)
occurrences all number	1	0	1
Oral fungal infection
subjects affected / exposed	1 / 36 (2.78%)	0 / 36 (0.00%)	0 / 37 (0.00%)
occurrences all number	1	0	0
Oral herpes
subjects affected / exposed	1 / 36 (2.78%)	0 / 36 (0.00%)	1 / 37 (2.70%)
occurrences all number	1	0	1
Pharyngitis
subjects affected / exposed	2 / 36 (5.56%)	3 / 36 (8.33%)	2 / 37 (5.41%)
occurrences all number	3	3	3
Pharyngotonsillitis
subjects affected / exposed	0 / 36 (0.00%)	1 / 36 (2.78%)	0 / 37 (0.00%)
occurrences all number	0	1	0
Pneumonia
subjects affected / exposed	0 / 36 (0.00%)	1 / 36 (2.78%)	0 / 37 (0.00%)
occurrences all number	0	1	0
Respiratory tract infection
subjects affected / exposed	0 / 36 (0.00%)	0 / 36 (0.00%)	1 / 37 (2.70%)
occurrences all number	0	0	1
Rhinitis
subjects affected / exposed	2 / 36 (5.56%)	1 / 36 (2.78%)	1 / 37 (2.70%)
occurrences all number	2	1	1
Sinusitis
subjects affected / exposed	0 / 36 (0.00%)	1 / 36 (2.78%)	0 / 37 (0.00%)
occurrences all number	0	1	0
Tonsillitis
subjects affected / exposed	0 / 36 (0.00%)	0 / 36 (0.00%)	1 / 37 (2.70%)
occurrences all number	0	0	1
Tooth abscess
subjects affected / exposed	1 / 36 (2.78%)	0 / 36 (0.00%)	0 / 37 (0.00%)
occurrences all number	1	0	0
Tooth infection
subjects affected / exposed	0 / 36 (0.00%)	0 / 36 (0.00%)	1 / 37 (2.70%)
occurrences all number	0	0	1
Upper respiratory tract infection
subjects affected / exposed	3 / 36 (8.33%)	2 / 36 (5.56%)	2 / 37 (5.41%)
occurrences all number	4	2	2
Urinary tract infection
subjects affected / exposed	2 / 36 (5.56%)	2 / 36 (5.56%)	0 / 37 (0.00%)
occurrences all number	2	2	0
Viral upper respiratory tract infection
subjects affected / exposed	1 / 36 (2.78%)	0 / 36 (0.00%)	0 / 37 (0.00%)
occurrences all number	1	0	0
Vulvovaginitis
subjects affected / exposed	0 / 36 (0.00%)	1 / 36 (2.78%)	0 / 37 (0.00%)
occurrences all number	0	1	0
Metabolism and nutrition disorders
Hypercholesterolaemia
subjects affected / exposed	1 / 36 (2.78%)	0 / 36 (0.00%)	0 / 37 (0.00%)
occurrences all number	1	0	0
Hypertriglyceridaemia
subjects affected / exposed	1 / 36 (2.78%)	1 / 36 (2.78%)	2 / 37 (5.41%)
occurrences all number	1	1	2
Hypoglycaemia
subjects affected / exposed	0 / 36 (0.00%)	1 / 36 (2.78%)	0 / 37 (0.00%)
occurrences all number	0	1	0
Increased appetite
subjects affected / exposed	1 / 36 (2.78%)	0 / 36 (0.00%)	0 / 37 (0.00%)
occurrences all number	1	0	0
Type 2 diabetes mellitus
subjects affected / exposed	0 / 36 (0.00%)	0 / 36 (0.00%)	1 / 37 (2.70%)
occurrences all number	0	0	1

More information

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Were there any global substantial amendments to the protocol? Yes

30 Sep 2010

Bone marrow edema at 6 months was added as an additional primary endpoint.

15 Dec 2010

1. The definition of AEs was expanded to include signs and symptoms resulting from exposure during breast feeding. 2. The definition of hospitalization was expanded to include hospitalization for observation without a medical AE. 3. Potential cases of Drug-Induced Liver Injury (DILI) were added to the protocol.

22 Aug 2012

1. Reporting of laboratory abnormalities that warranted temporary discontinuation of study medication was added. 2. Treated infections were added. 3. Addition of a urine Human Chorionic Gonadotrophin (HCG) pregnancy test for female subjects of childbearing potential at each visit.

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: An Exploratory Phase 2, Randomized, Double-blind, Multicenter Study To Assess The Effects Of Tofacitinib (CP-690,550) ON Magnetic Resonance Imaging Endpoints, In Methotrexate Naïve Subjects With Early Active Rheumatoid Arthritis

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Change From Baseline to Month 3 in Outcome Measures in Rheumatoid Arthritis Clinical Trials (OMERACT) Rheumatoid Arthritis Magnetic Resonance Imaging Score (RAMRIS) Wrist and Metacarpophalangeal (MCP) Synovitis

Primary: Change From Baseline to Month 3 in Outcome Measures in Rheumatoid Arthritis Clinical Trials (OMERACT) Rheumatoid Arthritis Magnetic Resonance Imaging Score (RAMRIS) Wrist and Metacarpophalangeal (MCP) Synovitis

Primary: Change From Baseline to Month 6 in OMERACT RAMRIS Wrist and MCP Bone Marrow Edema

Primary: Change From Baseline to Month 6 in OMERACT RAMRIS Wrist and MCP Bone Marrow Edema

Secondary: Change From Baseline to Months 1, 6, and 12 in OMERACT RAMRIS Wrist and MCP Synovitis

Secondary: Change From Baseline to Months 1, 6, and 12 in OMERACT RAMRIS Wrist and MCP Synovitis

Secondary: Change From Baseline to Months 1, 3, and 12 in OMERACT RAMRIS Bone Marrow Edema in Wrist and MCP

Secondary: Change From Baseline to Months 1, 3, and 12 in OMERACT RAMRIS Bone Marrow Edema in Wrist and MCP

Secondary: Change From Baseline to Months 1, 3, 6, and 12 in OMERACT RAMRIS Wrist and MCP Erosions

Secondary: Change From Baseline to Months 1, 3, 6, and 12 in OMERACT RAMRIS Wrist and MCP Erosions

Secondary: Modified Total Sharp Score (mTSS) at Months 6 and 12

Secondary: Modified Total Sharp Score (mTSS) at Months 6 and 12

Secondary: Change From Baseline to Months 6 and 12 in mTSS

Secondary: Change From Baseline to Months 6 and 12 in mTSS

Secondary: Joint Space Narrowing (JSN) Scores at Months 6 and 12

Secondary: Joint Space Narrowing (JSN) Scores at Months 6 and 12

Secondary: Change From Baseline to Months 6 and 12 in JSN Scores

Secondary: Change From Baseline to Months 6 and 12 in JSN Scores

Secondary: Erosion Scores at Months 6 and 12

Secondary: Erosion Scores at Months 6 and 12

Secondary: Change From Baseline to Months 6 and 12 in Erosion Score

Secondary: Change From Baseline to Months 6 and 12 in Erosion Score

Secondary: Percentage of Subjects With an American College of Rheumatology (ACR) 20 Percent (%) Improvement (ACR20) Response

Secondary: Percentage of Subjects With an American College of Rheumatology (ACR) 20 Percent (%) Improvement (ACR20) Response

Secondary: Percentage of Subjects With an ACR 50% Improvement (ACR50) Response

Secondary: Percentage of Subjects With an ACR 50% Improvement (ACR50) Response

Secondary: Percentage of Subjects With an ACR 70% Improvement (ACR70) Response

Secondary: Percentage of Subjects With an ACR 70% Improvement (ACR70) Response

Secondary: Disease Activity Score Based on 28-Joint Count and CRP (DAS28-3 [CRP])

Secondary: Disease Activity Score Based on 28-Joint Count and CRP (DAS28-3 [CRP])

Secondary: Change From Baseline in DAS28-3 (CRP)

Secondary: Change From Baseline in DAS28-3 (CRP)

Secondary: Disease Activity Score Based on 28-Joint Count and Erythrocyte Sedimentation Rate (DAS28-4 [ESR])

Secondary: Disease Activity Score Based on 28-Joint Count and Erythrocyte Sedimentation Rate (DAS28-4 [ESR])

Secondary: Change From Baseline in DAS28-4 (ESR)

Secondary: Change From Baseline in DAS28-4 (ESR)

Secondary: Percentage of Subjects With DAS28-3 (CRP) Response (Good or Moderate Improvement)

Secondary: Percentage of Subjects With DAS28-3 (CRP) Response (Good or Moderate Improvement)

Secondary: Percentage of Subjects With DAS28-3 (CRP) Score =<3.2

Secondary: Percentage of Subjects With DAS28-3 (CRP) Score =<3.2

Secondary: Percentage of Subjects With DAS28-3 (CRP) Score <2.6

Secondary: Percentage of Subjects With DAS28-3 (CRP) Score <2.6

Secondary: Percentage of Subjects With DAS28-4 (ESR) Response (Good or Moderate Improvement)

Secondary: Percentage of Subjects With DAS28-4 (ESR) Response (Good or Moderate Improvement)

Secondary: Percentage of Subjects With DAS28-4 (ESR) <=3.2

Secondary: Percentage of Subjects With DAS28-4 (ESR) <=3.2

Secondary: Percentage of Subjects With DAS28-4 (ESR) <2.6

Secondary: Percentage of Subjects With DAS28-4 (ESR) <2.6

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
An Exploratory Phase 2, Randomized, Double-blind, Multicenter Study To Assess The Effects Of Tofacitinib (CP-690,550) ON Magnetic Resonance Imaging Endpoints, In Methotrexate Naïve Subjects With Early Active Rheumatoid Arthritis