Trial Outcomes & Findings for Methotrexate Withdrawal Study of Tofacitinib Modified Release Formulation in Subjects With Rheumatoid Arthritis (NCT NCT02831855)

NCT ID: NCT02831855

Last Updated: 2019-12-04

Results Overview

DAS28 is a measure of disease activity in participants with rheumatoid arthritis. DAS28-4 (ESR) was calculated from swollen joint count (SJC) and tender/painful joint count (TJC) using 28 joints count, ESR (millimeters per hour \[mm/hr\]) and participant global assessment of arthritis (PtGA) on a 100 millimeter (mm) visual analog scale (VAS: scores ranging from 0 mm \[very well\] to 100 mm \[worst\], higher scores indicate worse health condition). Total DAS28-4 (ESR) score range: 0 (none) to 9.4 (extreme disease activity), higher score indicated more disease activity. DAS28-4 (ESR) less than or equal to (\<=) 3.2 implied low disease activity and greater than (\>) 3.2 to \<=5.1 implied moderate disease activity, \>5.1 implied high disease activity, and DAS28-4 (ESR) less than (\<) 2.6 implied remission. DAS28-4 (ESR) = 0.56\*sqrt(TJC28) + 0.28\*sqrt(SJC28) + 0.70\*In(ESR in mm/hour) + 0.014\*PtGA in mm; ln = natural logarithm, sqrt = square root of.

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 694 participants
• Primary outcome timeframe: Randomization (last non-missing measurement on or prior to the first dosing date in DB phase at Week 24), Week 48
• Results posted on: 2019-12-04

Participant Flow

Participant milestones

Measure	Open Label: Tofacitinib 11 mg + Methotrexate Participants with moderate to severe rheumatoid arthritis (RA) and who were insufficiently responding to their stable dose of methotrexate treatment previous to enrollment in this study, received Tofacitinib modified release (MR) 11 milligram (mg) tablet once daily (QD) with methotrexate at their previous stable dose for 24 weeks in open label phase (OL).	Double Blind: Tofacitinib 11 mg + Methotrexate Placebo Participants with low disease activity (LDA) at the end of open label phase were randomized to receive Tofacitinib MR 11 mg tablet once daily with matching placebo to blinded methotrexate at their previously stabilized dose for 24 weeks in double blind phase.	Double Blind: Tofacitinib 11mg + Methotrexate Participants with LDA at the end of open label phase were randomized to receive Tofacitinib MR 11 mg tablet once daily with blinded methotrexate at their previously stabilized dose for 24 weeks in double blind phase.
Open Label Phase (24 Weeks) STARTED	694	0	0
Open Label Phase (24 Weeks) COMPLETED	623	0	0
Open Label Phase (24 Weeks) NOT COMPLETED	71	0	0
Double Blind Phase (24 Weeks) STARTED	0	267	266
Double Blind Phase (24 Weeks) Treated	0	264	266
Double Blind Phase (24 Weeks) COMPLETED	0	238	247
Double Blind Phase (24 Weeks) NOT COMPLETED	0	29	19

Reasons for withdrawal

Measure	Open Label: Tofacitinib 11 mg + Methotrexate Participants with moderate to severe rheumatoid arthritis (RA) and who were insufficiently responding to their stable dose of methotrexate treatment previous to enrollment in this study, received Tofacitinib modified release (MR) 11 milligram (mg) tablet once daily (QD) with methotrexate at their previous stable dose for 24 weeks in open label phase (OL).	Double Blind: Tofacitinib 11 mg + Methotrexate Placebo Participants with low disease activity (LDA) at the end of open label phase were randomized to receive Tofacitinib MR 11 mg tablet once daily with matching placebo to blinded methotrexate at their previously stabilized dose for 24 weeks in double blind phase.	Double Blind: Tofacitinib 11mg + Methotrexate Participants with LDA at the end of open label phase were randomized to receive Tofacitinib MR 11 mg tablet once daily with blinded methotrexate at their previously stabilized dose for 24 weeks in double blind phase.
Open Label Phase (24 Weeks) Adverse Event	39	0	0
Open Label Phase (24 Weeks) Lost to Follow-up	8	0	0
Open Label Phase (24 Weeks) Insufficient Clinical Response	7	0	0
Open Label Phase (24 Weeks) Medication error,no linked adverse event	2	0	0
Open Label Phase (24 Weeks) Protocol Violation	5	0	0
Open Label Phase (24 Weeks) Withdrawal by Subject	6	0	0
Open Label Phase (24 Weeks) Other	4	0	0
Double Blind Phase (24 Weeks) Adverse Event	0	6	6
Double Blind Phase (24 Weeks) Death	0	0	2
Double Blind Phase (24 Weeks) Lost to Follow-up	0	1	1
Double Blind Phase (24 Weeks) Screen Failure	0	1	0
Double Blind Phase (24 Weeks) Withdrawal by Subject	0	5	2
Double Blind Phase (24 Weeks) Other	0	2	5
Double Blind Phase (24 Weeks) Insufficient Clinical Response	0	6	1
Double Blind Phase (24 Weeks) Protocol Violation	0	5	2
Double Blind Phase (24 Weeks) Randomized but not Treated	0	3	0

Baseline Characteristics

Methotrexate Withdrawal Study of Tofacitinib Modified Release Formulation in Subjects With Rheumatoid Arthritis

Baseline characteristics by cohort

Measure	Open Label: Tofacitinib 11 mg + Methotrexate n=694 Participants Participants with moderate to severe rheumatoid arthritis (RA) and who were insufficiently responding to their stable dose of methotrexate treatment previous to enrollment in this study, received Tofacitinib modified release (MR) 11 milligram (mg) tablet once daily (QD) with methotrexate at their previous stable dose for 24 weeks in open label phase (OL).
Age, Continuous	56.77 Years STANDARD_DEVIATION 11.83 • n=5 Participants
Sex: Female, Male Female	532 Participants n=5 Participants
Sex: Female, Male Male	162 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	59 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	635 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race/Ethnicity, Customized Asian	37 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	33 Participants n=5 Participants
Race/Ethnicity, Customized White	594 Participants n=5 Participants
Race/Ethnicity, Customized Others	30 Participants n=5 Participants

PRIMARY outcome

Timeframe: Randomization (last non-missing measurement on or prior to the first dosing date in DB phase at Week 24), Week 48

Population: Double-Blind Period Full Analysis Set (FAS-DB) included all participants who received at least 1 dose of investigational drug during the OL phase, were randomized and received at least 1 dose of the randomized investigational drug regimen during DB phase. Overall number of participants analyzed=participants evaluable for this outcome measure.

DAS28 is a measure of disease activity in participants with rheumatoid arthritis. DAS28-4 (ESR) was calculated from swollen joint count (SJC) and tender/painful joint count (TJC) using 28 joints count, ESR (millimeters per hour [mm/hr]) and participant global assessment of arthritis (PtGA) on a 100 millimeter (mm) visual analog scale (VAS: scores ranging from 0 mm [very well] to 100 mm [worst], higher scores indicate worse health condition). Total DAS28-4 (ESR) score range: 0 (none) to 9.4 (extreme disease activity), higher score indicated more disease activity. DAS28-4 (ESR) less than or equal to (<=) 3.2 implied low disease activity and greater than (>) 3.2 to <=5.1 implied moderate disease activity, >5.1 implied high disease activity, and DAS28-4 (ESR) less than (<) 2.6 implied remission. DAS28-4 (ESR) = 0.56*sqrt(TJC28) + 0.28*sqrt(SJC28) + 0.70*In(ESR in mm/hour) + 0.014*PtGA in mm; ln = natural logarithm, sqrt = square root of.

Outcome measures

Measure	Double Blind: Tofacitinib 11 mg + Methotrexate Placebo n=235 Participants Participants with low disease activity (LDA) at the end of open label phase were randomized to receive Tofacitinib MR 11 mg tablet once daily with matching placebo to blinded methotrexate at their previously stabilized dose for 24 weeks in double blind phase.	Double Blind: Tofacitinib 11mg + Methotrexate n=237 Participants Participants with LDA at the end of open label phase were randomized to receive Tofacitinib MR 11 mg tablet once daily with blinded methotrexate at their previously stabilized dose for 24 weeks in double blind phase.	Double Blind: Tofacitinib 11mg + Methotrexate Participants with LDA at the end of open label phase were randomized to receive Tofacitinib MR 11 mg tablet once daily with blinded methotrexate at their previously stabilized dose for 24 weeks in double blind phase.
Double Blind Phase: Change From Randomization in Disease Activity Score in 28 Joints Using 4 Variables (DAS28-4) (Erythrocyte Sedimentation Rate [ESR]) at Week 48	0.33 units on a scale Standard Error 0.07	0.03 units on a scale Standard Error 0.07	—

SECONDARY outcome

Timeframe: Randomization (last non-missing measurement on or prior to the first dosing date in DB phase at Week 24), Week 36

Population: FAS-DB included all participants who received at least 1 dose of investigational drug during the OL phase, were randomized and received at least 1 dose of the randomized investigational drug regimen during DB phase. Overall number of participants analyzed=participants evaluable for this outcome measure.

DAS28 is a measure of disease activity in participants with rheumatoid arthritis. DAS28-4 (ESR) was calculated from SJC and TJC using 28 joints count, ESR (mm/hr) and PtGA on a 100 millimeter (mm) VAS (VAS: scores ranging from 0 mm [very well] to 100 mm [worst], higher scores indicate worse health condition). Total DAS28-4 (ESR) score range: 0 (none) to 9.4 (extreme disease activity), higher score indicated more disease activity. DAS28-4 (ESR) less than or equal to (<=) 3.2 implied low disease activity and greater than (>) 3.2 to <=5.1 implied moderate disease activity, >5.1 implied high disease activity, and DAS28-4 (ESR) less than (<) 2.6 implied remission. DAS28-4 (ESR) = 0.56*sqrt(TJC28) + 0.28*sqrt(SJC28) + 0.70*In(ESR in mm/hour) + 0.014*PtGA in mm; ln = natural logarithm, sqrt = square root of.

Outcome measures

Measure	Double Blind: Tofacitinib 11 mg + Methotrexate Placebo n=253 Participants Participants with low disease activity (LDA) at the end of open label phase were randomized to receive Tofacitinib MR 11 mg tablet once daily with matching placebo to blinded methotrexate at their previously stabilized dose for 24 weeks in double blind phase.	Double Blind: Tofacitinib 11mg + Methotrexate n=253 Participants Participants with LDA at the end of open label phase were randomized to receive Tofacitinib MR 11 mg tablet once daily with blinded methotrexate at their previously stabilized dose for 24 weeks in double blind phase.	Double Blind: Tofacitinib 11mg + Methotrexate Participants with LDA at the end of open label phase were randomized to receive Tofacitinib MR 11 mg tablet once daily with blinded methotrexate at their previously stabilized dose for 24 weeks in double blind phase.
Double Blind Phase: Change From Randomization in DAS28-4 ESR at Week 36	0.40 units on a scale Standard Error 0.07	0.18 units on a scale Standard Error 0.07	—

SECONDARY outcome

Timeframe: Randomization (last non-missing measurement on or prior to the first dosing date in DB phase at Week 24), Weeks 36 and 48

Population: FAS-DB was analyzed. Here, 'Number analyzed' = Participants evaluable for this outcome measure at specified time points.

DAS28 is a measure of disease activity in participants with rheumatoid arthritis. DAS28-4 (CRP) was calculated from SJC and TJC using 28 joints count, CRP (milligrams per liter [mg/L]) and PtGA on a 100 mm VAS (VAS: scores ranging from 0 mm [very well] to 100 mm [worst], higher scores indicate worse health condition). Total DAS28-4 (CRP) score range: 0 (none) to 9.4 (extreme disease activity), higher score indicated more disease activity. DAS28-4 (CRP) <= 3.2 implied low disease activity and > 3.2 to <=5.1 implied moderate disease activity, >5.1 implied high disease activity, and DAS28-4 (CRP) < 2.6 implied remission. DAS28-4 (CRP) = 0.56*sqrt(TJC28) + 0.28*sqrt(SJC28) + 0.36*ln(CRP in mg/L +1) + 0.014*PtGA in mm+ 0.96; ln = natural logarithm, sqrt = square root of.

Outcome measures

Measure	Double Blind: Tofacitinib 11 mg + Methotrexate Placebo n=264 Participants Participants with low disease activity (LDA) at the end of open label phase were randomized to receive Tofacitinib MR 11 mg tablet once daily with matching placebo to blinded methotrexate at their previously stabilized dose for 24 weeks in double blind phase.	Double Blind: Tofacitinib 11mg + Methotrexate n=266 Participants Participants with LDA at the end of open label phase were randomized to receive Tofacitinib MR 11 mg tablet once daily with blinded methotrexate at their previously stabilized dose for 24 weeks in double blind phase.	Double Blind: Tofacitinib 11mg + Methotrexate Participants with LDA at the end of open label phase were randomized to receive Tofacitinib MR 11 mg tablet once daily with blinded methotrexate at their previously stabilized dose for 24 weeks in double blind phase.
Double Blind Phase: Change From Randomization in DAS28-4 (C-reactive Protein [CRP]) at Weeks 36 and 48 Change at Week 36	0.38 units on a scale Standard Error 0.06	0.13 units on a scale Standard Error 0.06	—
Double Blind Phase: Change From Randomization in DAS28-4 (C-reactive Protein [CRP]) at Weeks 36 and 48 Change at Week 48	0.29 units on a scale Standard Error 0.06	0.01 units on a scale Standard Error 0.06	—

SECONDARY outcome

Timeframe: Randomization (last non-missing measurement on or prior to the first dosing date in DB phase at Week 24), Weeks 36 and 48

Population: FAS-DB was analyzed. Here, 'Number analyzed' = Participants evaluable for this outcome measure at specified time points.

CDAI was calculated from tender and swollen joints using 28 joint count, PtGA and physician global assessment of arthritis (PhyGA). PtGA and PhyGA both were assessed on 0-10 centimeter (cm) VAS scale (VAS: scores ranging from 0 cm [very well] to 10 cm [worst]), where higher scores indicated greater affliction due to disease activity). CDAI total score ranged from 0 to 76, where higher scores indicated higher disease activity. CDAI score of <=10 indicated low disease activity and a score of <= 2.8 indicated remission. CDAI = (28TJC) + (28SJC) + (PhyGA in cm) + (PtGA in cm).

Outcome measures

Measure	Double Blind: Tofacitinib 11 mg + Methotrexate Placebo n=264 Participants Participants with low disease activity (LDA) at the end of open label phase were randomized to receive Tofacitinib MR 11 mg tablet once daily with matching placebo to blinded methotrexate at their previously stabilized dose for 24 weeks in double blind phase.	Double Blind: Tofacitinib 11mg + Methotrexate n=266 Participants Participants with LDA at the end of open label phase were randomized to receive Tofacitinib MR 11 mg tablet once daily with blinded methotrexate at their previously stabilized dose for 24 weeks in double blind phase.	Double Blind: Tofacitinib 11mg + Methotrexate Participants with LDA at the end of open label phase were randomized to receive Tofacitinib MR 11 mg tablet once daily with blinded methotrexate at their previously stabilized dose for 24 weeks in double blind phase.
Double Blind Phase: Change From Randomization in Clinical Disease Activity Index (CDAI) at Weeks 36 and 48 Change at Week 36	3.58 units on a scale Standard Error 0.49	1.84 units on a scale Standard Error 0.48	—
Double Blind Phase: Change From Randomization in Clinical Disease Activity Index (CDAI) at Weeks 36 and 48 Change at Week 48	2.97 units on a scale Standard Error 0.48	0.84 units on a scale Standard Error 0.47	—

SECONDARY outcome

Timeframe: Randomization (last non-missing measurement on or prior to the first dosing date in DB phase at Week 24), Weeks 36 and 48

Population: FAS-DB was analyzed. Here, 'Number analyzed' = Participants evaluable for this outcome measure at specified time points.

SDAI was calculated from tender and swollen joints using 28 joint count, PtGA, PhyGA and CRP (in mg/dL). PtGA and PhyGA both were assessed on 0-10 cm VAS scale (VAS: scores ranging from 0 cm [very well] to 10 cm [worst]), where higher scores indicated greater affliction due to disease activity). SDAI total score ranged from 0 to 86, where higher scores indicated higher disease activity. SDAI score of <=11 indicates low disease activity and a score of <=3.3 indicates remission. SDAI = (28TJC) + (28SJC) + (PhyGA in cm) + (PtGA in cm) + (CRP in mg/dL).

Outcome measures

Measure	Double Blind: Tofacitinib 11 mg + Methotrexate Placebo n=264 Participants Participants with low disease activity (LDA) at the end of open label phase were randomized to receive Tofacitinib MR 11 mg tablet once daily with matching placebo to blinded methotrexate at their previously stabilized dose for 24 weeks in double blind phase.	Double Blind: Tofacitinib 11mg + Methotrexate n=266 Participants Participants with LDA at the end of open label phase were randomized to receive Tofacitinib MR 11 mg tablet once daily with blinded methotrexate at their previously stabilized dose for 24 weeks in double blind phase.	Double Blind: Tofacitinib 11mg + Methotrexate Participants with LDA at the end of open label phase were randomized to receive Tofacitinib MR 11 mg tablet once daily with blinded methotrexate at their previously stabilized dose for 24 weeks in double blind phase.
Double Blind Phase: Change From Randomization in Simplified Disease Activity Index (SDAI) at Weeks 36 and 48 Change at Week 36	3.83 units on a scale Standard Error 0.52	1.88 units on a scale Standard Error 0.51	—
Double Blind Phase: Change From Randomization in Simplified Disease Activity Index (SDAI) at Weeks 36 and 48 Change at Week 48	3.16 units on a scale Standard Error 0.50	0.94 units on a scale Standard Error 0.49	—

SECONDARY outcome

Timeframe: Weeks 36 and 48

Population: FAS-DB included all participants who received at least 1 dose of investigational drug during the OL phase, were randomized and received at least 1 dose of the randomized investigational drug regimen during DB phase. Non-responder imputation (NRI) method was used to impute missing data.

DAS28 is a measure of disease activity in participants with rheumatoid arthritis. DAS28-4 (ESR) was calculated from SJC and TJC using 28 joints count, ESR (mm/hr) and PtGA on a 100 mm VAS (VAS: scores ranging from 0 mm [very well] to 100 mm [worst], higher scores indicated worse health condition). Total DAS28-4 (ESR) score range: 0 (none) to 9.4 (extreme disease activity), higher score indicated more disease activity. DAS28-4 (ESR) <=3.2 implied low disease activity and >3.2 to <=5.1 implied moderate disease activity, >5.1 implied high disease activity, and DAS28-4 (ESR) <2.6 implied remission. DAS28-4 (ESR) = 0.56*sqrt(TJC28) + 0.28*sqrt(SJC28) + 0.70*In(ESR in mm/hour) + 0.014*PtGA in mm; ln = natural logarithm, sqrt = square root of.

Outcome measures

Measure	Double Blind: Tofacitinib 11 mg + Methotrexate Placebo n=264 Participants Participants with low disease activity (LDA) at the end of open label phase were randomized to receive Tofacitinib MR 11 mg tablet once daily with matching placebo to blinded methotrexate at their previously stabilized dose for 24 weeks in double blind phase.	Double Blind: Tofacitinib 11mg + Methotrexate n=266 Participants Participants with LDA at the end of open label phase were randomized to receive Tofacitinib MR 11 mg tablet once daily with blinded methotrexate at their previously stabilized dose for 24 weeks in double blind phase.	Double Blind: Tofacitinib 11mg + Methotrexate Participants with LDA at the end of open label phase were randomized to receive Tofacitinib MR 11 mg tablet once daily with blinded methotrexate at their previously stabilized dose for 24 weeks in double blind phase.
Double Blind Phase: Percentage of Participants With Low Disease Activity (LDA) Assessed by DAS28-4 (ESR) Less Than or Equal to (<=) 3.2 at Weeks 36 and 48 Week 36	42.42 percentage of participants	48.12 percentage of participants	—
Double Blind Phase: Percentage of Participants With Low Disease Activity (LDA) Assessed by DAS28-4 (ESR) Less Than or Equal to (<=) 3.2 at Weeks 36 and 48 Week 48	45.08 percentage of participants	49.62 percentage of participants	—

SECONDARY outcome

Timeframe: Weeks 36 and 48

Population: FAS-DB included all participants who received at least 1 dose of investigational drug during the OL phase, were randomized and received at least 1 dose of the randomized investigational drug regimen during DB phase. NRI method was used to impute missing data.

DAS28 is a measure of disease activity in participants with rheumatoid arthritis. DAS28-4 (CRP) was calculated from SJC and TJC using 28 joints count, CRP (mg/L) and PtGA on a 100 mm VAS (VAS: scores ranging from 0 mm [very well] to 100 mm [worst], higher scores indicate worse health condition). Total DAS28-4 (CRP) score range: 0 (none) to 9.4 (extreme disease activity), higher score indicated more disease activity. DAS28-4 (CRP) <=3.2 implied low disease activity and >3.2 to <=5.1 implied moderate disease activity, >5.1 implied high disease activity, and DAS28-4 (CRP) <2.6 implied remission. DAS28-4 (CRP) = 0.56*sqrt(TJC28) + 0.28*sqrt(SJC28) + 0.36*ln(CRP in mg/L +1) + 0.014*PtGA in mm+ 0.96; ln = natural logarithm, sqrt = square root of.

Outcome measures

Measure	Double Blind: Tofacitinib 11 mg + Methotrexate Placebo n=264 Participants Participants with low disease activity (LDA) at the end of open label phase were randomized to receive Tofacitinib MR 11 mg tablet once daily with matching placebo to blinded methotrexate at their previously stabilized dose for 24 weeks in double blind phase.	Double Blind: Tofacitinib 11mg + Methotrexate n=266 Participants Participants with LDA at the end of open label phase were randomized to receive Tofacitinib MR 11 mg tablet once daily with blinded methotrexate at their previously stabilized dose for 24 weeks in double blind phase.	Double Blind: Tofacitinib 11mg + Methotrexate Participants with LDA at the end of open label phase were randomized to receive Tofacitinib MR 11 mg tablet once daily with blinded methotrexate at their previously stabilized dose for 24 weeks in double blind phase.
Double Blind Phase: Percentage of Participants With LDA Assessed by DAS28-4 (CRP) <=3.2 at Weeks 36 and 48 Week 36	65.53 percentage of participants	70.68 percentage of participants	—
Double Blind Phase: Percentage of Participants With LDA Assessed by DAS28-4 (CRP) <=3.2 at Weeks 36 and 48 Week 48	65.91 percentage of participants	74.44 percentage of participants	—

SECONDARY outcome

Timeframe: Weeks 36 and 48

Population: FAS-DB included all participants who received at least 1 dose of investigational drug during the OL phase, were randomized and received at least 1 dose of the randomized investigational drug regimen during DB phase. NRI method was used to impute missing data.

CDAI was calculated from tender and swollen joints using 28 joint count, PtGA and PhyGA. PtGA and PhyGA both were assessed on 0-10 cm VAS scale (VAS: scores ranging from 0 cm [very well] to 10 cm [worst]), where higher scores indicated greater affliction due to disease activity). CDAI total score ranged from 0 to 76, where higher scores indicated higher disease activity. CDAI score of <=10 indicated low disease activity and a score of <= 2.8 indicated remission. Percentage of participants with CDAI <=10 were reported. CDAI = (28TJC) + (28SJC) + (PhyGA in cm) + (PtGA in cm).

Outcome measures

Measure	Double Blind: Tofacitinib 11 mg + Methotrexate Placebo n=264 Participants Participants with low disease activity (LDA) at the end of open label phase were randomized to receive Tofacitinib MR 11 mg tablet once daily with matching placebo to blinded methotrexate at their previously stabilized dose for 24 weeks in double blind phase.	Double Blind: Tofacitinib 11mg + Methotrexate n=266 Participants Participants with LDA at the end of open label phase were randomized to receive Tofacitinib MR 11 mg tablet once daily with blinded methotrexate at their previously stabilized dose for 24 weeks in double blind phase.	Double Blind: Tofacitinib 11mg + Methotrexate Participants with LDA at the end of open label phase were randomized to receive Tofacitinib MR 11 mg tablet once daily with blinded methotrexate at their previously stabilized dose for 24 weeks in double blind phase.
Double Blind Phase: Percentage of Participants With LDA Assessed by CDAI <=10 at Weeks 36 and 48 Week 36	66.29 percentage of participants	73.68 percentage of participants	—
Double Blind Phase: Percentage of Participants With LDA Assessed by CDAI <=10 at Weeks 36 and 48 Week 48	65.15 percentage of participants	77.07 percentage of participants	—

SECONDARY outcome

Timeframe: Weeks 36 and 48

Population: FAS-DB included all participants who received at least 1 dose of investigational drug during the OL phase, were randomized and received at least 1 dose of the randomized investigational drug regimen during DB phase. NRI method was used to impute missing data.

SDAI was calculated from tender and swollen joints using 28 joint count, PtGA, PhyGA and CRP (in mg/dL). PtGA and PhyGA both were assessed on 0-10 cm VAS scale (VAS: scores ranging from 0 cm [very well] to 10 cm [worst]), where higher scores indicated greater affliction due to disease activity). SDAI total score ranged from 0 to 86, where higher scores indicated higher disease activity. SDAI score of <=11 indicated low disease activity and a score of <=3.3 indicated remission. SDAI = (28TJC) + (28SJC) + (PhyGA in cm) + (PtGA in cm) + (CRP in mg/dL).

Outcome measures

Measure	Double Blind: Tofacitinib 11 mg + Methotrexate Placebo n=264 Participants Participants with low disease activity (LDA) at the end of open label phase were randomized to receive Tofacitinib MR 11 mg tablet once daily with matching placebo to blinded methotrexate at their previously stabilized dose for 24 weeks in double blind phase.	Double Blind: Tofacitinib 11mg + Methotrexate n=266 Participants Participants with LDA at the end of open label phase were randomized to receive Tofacitinib MR 11 mg tablet once daily with blinded methotrexate at their previously stabilized dose for 24 weeks in double blind phase.	Double Blind: Tofacitinib 11mg + Methotrexate Participants with LDA at the end of open label phase were randomized to receive Tofacitinib MR 11 mg tablet once daily with blinded methotrexate at their previously stabilized dose for 24 weeks in double blind phase.
Double Blind Phase: Percentage of Participants With LDA Assessed by SDAI <=11 at Weeks 36 and 48 Week 36	66.29 percentage of participants	73.31 percentage of participants	—
Double Blind Phase: Percentage of Participants With LDA Assessed by SDAI <=11 at Weeks 36 and 48 Week 48	66.29 percentage of participants	76.32 percentage of participants	—

SECONDARY outcome

Timeframe: Weeks 36 and 48

Population: FAS-DB included all participants who received at least 1 dose of investigational drug during the OL phase, were randomized and received at least 1 dose of the randomized investigational drug regimen during DB phase. NRI method was used to impute missing data.

ACR-EULAR Boolean remission was when a participant satisfied all of the following: tender joint count, swollen joint count (both based on a 28-joint assessment), CRP (in mg/dL), and PtGA (VAS: 0 cm [very well] to 10 cm [worst], higher scores indicated worse health condition) and all scores were <=1.

Outcome measures

Measure	Double Blind: Tofacitinib 11 mg + Methotrexate Placebo n=264 Participants Participants with low disease activity (LDA) at the end of open label phase were randomized to receive Tofacitinib MR 11 mg tablet once daily with matching placebo to blinded methotrexate at their previously stabilized dose for 24 weeks in double blind phase.	Double Blind: Tofacitinib 11mg + Methotrexate n=266 Participants Participants with LDA at the end of open label phase were randomized to receive Tofacitinib MR 11 mg tablet once daily with blinded methotrexate at their previously stabilized dose for 24 weeks in double blind phase.	Double Blind: Tofacitinib 11mg + Methotrexate Participants with LDA at the end of open label phase were randomized to receive Tofacitinib MR 11 mg tablet once daily with blinded methotrexate at their previously stabilized dose for 24 weeks in double blind phase.
Double Blind Phase: Percentage of Participants With Remission Assessed by American College of Rheumatology-European League Against Rheumatism (ACR-EULAR) Boolean at Weeks 36 and 48 Week 36	15.53 percentage of participants	24.06 percentage of participants	—
Double Blind Phase: Percentage of Participants With Remission Assessed by American College of Rheumatology-European League Against Rheumatism (ACR-EULAR) Boolean at Weeks 36 and 48 Week 48	22.35 percentage of participants	23.68 percentage of participants	—

SECONDARY outcome

Timeframe: Weeks 36 and 48

Population: FAS-DB included all participants who received at least 1 dose of investigational drug during the OL phase, were randomized and received at least 1 dose of the randomized investigational drug regimen during DB phase. NRI method was used to impute missing data.

DAS28 is a measure of disease activity in participants with rheumatoid arthritis. DAS28-4 (ESR) was calculated from SJC and TJC using 28 joints count, ESR (mm/hr) and PtGA on a 100 mm VAS (VAS: scores ranging from 0 mm [very well] to 100 mm [worst], higher scores indicate worse health condition). Total DAS28-4 (ESR) score range: 0 (none) to 9.4 (extreme disease activity), higher score indicated more disease activity. DAS28-4 (ESR) <= 3.2 implied low disease activity and >3.2 to <=5.1 implied moderate disease activity, >5.1 implied high disease activity, and DAS28-4 (ESR) <2.6 implied remission. DAS28-4 (ESR) = 0.56*sqrt(TJC28) + 0.28*sqrt(SJC28) + 0.70*In(ESR in mm/hour) + 0.014*PtGA in mm. Percentage of participants with DAS remission (DAS28-4-ESR<2.6) were reported in this outcome measure.

Outcome measures

Measure	Double Blind: Tofacitinib 11 mg + Methotrexate Placebo n=264 Participants Participants with low disease activity (LDA) at the end of open label phase were randomized to receive Tofacitinib MR 11 mg tablet once daily with matching placebo to blinded methotrexate at their previously stabilized dose for 24 weeks in double blind phase.	Double Blind: Tofacitinib 11mg + Methotrexate n=266 Participants Participants with LDA at the end of open label phase were randomized to receive Tofacitinib MR 11 mg tablet once daily with blinded methotrexate at their previously stabilized dose for 24 weeks in double blind phase.	Double Blind: Tofacitinib 11mg + Methotrexate Participants with LDA at the end of open label phase were randomized to receive Tofacitinib MR 11 mg tablet once daily with blinded methotrexate at their previously stabilized dose for 24 weeks in double blind phase.
Double Blind Phase: Percentage of Participants With Remission Assessed by DAS28-4 (ESR) Less Than [<] 2.6 at Weeks 36 and 48 Week 36	20.45 percentage of participants	28.57 percentage of participants	—
Double Blind Phase: Percentage of Participants With Remission Assessed by DAS28-4 (ESR) Less Than [<] 2.6 at Weeks 36 and 48 Week 48	23.86 percentage of participants	30.08 percentage of participants	—

SECONDARY outcome

Timeframe: Weeks 36 and 48

Population: FAS-DB included all participants who received at least 1 dose of investigational drug during the OL phase, were randomized and received at least 1 dose of the randomized investigational drug regimen during DB phase. NRI method was used to impute missing data.

DAS28 is a measure of disease activity in participants with rheumatoid arthritis. DAS28-4 (CRP) was calculated from SJC and TJC using 28 joints count, CRP (mg/L) and PtGA on a 100 mm VAS (VAS: scores ranging from 0 mm [very well] to 100 mm [worst], higher scores indicate worse health condition). Total DAS28-4 (CRP) score range: 0 (none) to 9.4 (extreme disease activity), higher score indicated more disease activity. DAS28-4 (CRP) <=3.2 implied low disease activity and >3.2 to <=5.1 implied moderate disease activity, >5.1 implied high disease activity, and DAS28-4 (CRP) <2.6 implied remission. DAS28-4 (CRP) = 0.56*sqrt(TJC28) + 0.28*sqrt(SJC28) + 0.36*ln(CRP in mg/l +1) + 0.014*PtGA in mm+ 0.96. Percentage of participants with DAS remission (DAS28-4-CRP<2.6) were reported in this outcome measure.

Outcome measures

Measure	Double Blind: Tofacitinib 11 mg + Methotrexate Placebo n=264 Participants Participants with low disease activity (LDA) at the end of open label phase were randomized to receive Tofacitinib MR 11 mg tablet once daily with matching placebo to blinded methotrexate at their previously stabilized dose for 24 weeks in double blind phase.	Double Blind: Tofacitinib 11mg + Methotrexate n=266 Participants Participants with LDA at the end of open label phase were randomized to receive Tofacitinib MR 11 mg tablet once daily with blinded methotrexate at their previously stabilized dose for 24 weeks in double blind phase.	Double Blind: Tofacitinib 11mg + Methotrexate Participants with LDA at the end of open label phase were randomized to receive Tofacitinib MR 11 mg tablet once daily with blinded methotrexate at their previously stabilized dose for 24 weeks in double blind phase.
Double Blind Phase: Percentage of Participants With Remission Assessed by DAS28-4 (CRP) <2.6 at Weeks 36 and 48 Week 36	50.00 percentage of participants	55.64 percentage of participants	—
Double Blind Phase: Percentage of Participants With Remission Assessed by DAS28-4 (CRP) <2.6 at Weeks 36 and 48 Week 48	50.38 percentage of participants	54.51 percentage of participants	—

SECONDARY outcome

Timeframe: Weeks 36 and 48

Population: FAS-DB included all participants who received at least 1 dose of investigational drug during the OL phase, were randomized and received at least 1 dose of the randomized investigational drug regimen during DB phase. NRI method was used to impute missing data.

CDAI was calculated from tender and swollen joints using 28 joint count, PtGA and PhyGA. PtGA and PhyGA both were assessed on 0-10 cm VAS scale (VAS: scores ranging from 0 cm [very well] to 10 cm [worst]), where higher scores indicated greater affliction due to disease activity). CDAI total score ranged from 0 to 76, where higher scores indicated higher disease activity. CDAI score of <=10 indicated low disease activity and a score of <= 2.8 indicated remission. CDAI = (28TJC) + (28SJC) + (PhyGA in cm) + (PtGA in cm).

Outcome measures

Measure	Double Blind: Tofacitinib 11 mg + Methotrexate Placebo n=264 Participants Participants with low disease activity (LDA) at the end of open label phase were randomized to receive Tofacitinib MR 11 mg tablet once daily with matching placebo to blinded methotrexate at their previously stabilized dose for 24 weeks in double blind phase.	Double Blind: Tofacitinib 11mg + Methotrexate n=266 Participants Participants with LDA at the end of open label phase were randomized to receive Tofacitinib MR 11 mg tablet once daily with blinded methotrexate at their previously stabilized dose for 24 weeks in double blind phase.	Double Blind: Tofacitinib 11mg + Methotrexate Participants with LDA at the end of open label phase were randomized to receive Tofacitinib MR 11 mg tablet once daily with blinded methotrexate at their previously stabilized dose for 24 weeks in double blind phase.
Double Blind Phase: Percentage of Participants With Remission Assessed by CDAI <=2.8 at Weeks 36 and 48 Week 36	23.48 percentage of participants	32.33 percentage of participants	—
Double Blind Phase: Percentage of Participants With Remission Assessed by CDAI <=2.8 at Weeks 36 and 48 Week 48	28.41 percentage of participants	30.83 percentage of participants	—

SECONDARY outcome

Timeframe: Weeks 36 and 48

Population: FAS-DB included all participants who received at least 1 dose of investigational drug during the OL phase, were randomized and received at least 1 dose of the randomized investigational drug regimen during DB phase. NRI method was used to impute missing data.

SDAI was calculated from tender and swollen joints using 28 joint count, PtGA, PhyGA and CRP (in mg/dL). PtGA and PhyGA both were assessed on 0-10 cm VAS scale (VAS: scores ranging from 0 cm [very well] to 10 cm [worst]), where higher scores indicated greater affliction due to disease activity). SDAI total score ranged from 0 to 86, where higher scores indicated higher disease activity. SDAI score of <=11 indicates low disease activity and a score of <=3.3 indicates remission. SDAI = (28TJC) + (28SJC) + (PhyGA in cm) + (PtGA in cm) + (CRP in mg/dL).

Outcome measures

Measure	Double Blind: Tofacitinib 11 mg + Methotrexate Placebo n=264 Participants Participants with low disease activity (LDA) at the end of open label phase were randomized to receive Tofacitinib MR 11 mg tablet once daily with matching placebo to blinded methotrexate at their previously stabilized dose for 24 weeks in double blind phase.	Double Blind: Tofacitinib 11mg + Methotrexate n=266 Participants Participants with LDA at the end of open label phase were randomized to receive Tofacitinib MR 11 mg tablet once daily with blinded methotrexate at their previously stabilized dose for 24 weeks in double blind phase.	Double Blind: Tofacitinib 11mg + Methotrexate Participants with LDA at the end of open label phase were randomized to receive Tofacitinib MR 11 mg tablet once daily with blinded methotrexate at their previously stabilized dose for 24 weeks in double blind phase.
Double Blind Phase: Percentage of Participants With Remission Assessed by SDAI <=3.3 at Weeks 36 and 48 Week 36	22.73 percentage of participants	31.58 percentage of participants	—
Double Blind Phase: Percentage of Participants With Remission Assessed by SDAI <=3.3 at Weeks 36 and 48 Week 48	28.79 percentage of participants	31.95 percentage of participants	—

SECONDARY outcome

Timeframe: Baseline (Day 1), Weeks 36 and 48

Population: FAS-DB included all participants who received at least 1 dose of investigational drug during the OL phase, were randomized and received at least 1 dose of the randomized investigational drug regimen during DB phase. NRI method was used to impute missing data.

Participants with 20% improvement in tender and swollen joint counts and 20% improvement in at least 3 of the 5 measures: PtGA, PhyGA, participant's assessment of arthritis pain, Health Assessment Questionnaire-Disability Index (HAQ-DI) and CRP. PtGA: participant assessed health on VAS, 0 mm (very well) to 100 mm (worst health condition), higher scores = worse condition. PhyGA: physician judged participants' pain on VAS, 0 (no pain) to 100 mm (extreme pain), higher scores = more pain. Participant's assessment of arthritis pain: participant assessed pain on VAS, 0 mm (no pain) to 100 mm (most severe pain), higher score = more pain. HAQ-DI: functional disability evaluation, score: 0 (no difficulty) to 3 (extreme difficulty), higher score implied more disability. The improvement was relative to baseline (Day 1).

Outcome measures

Measure	Double Blind: Tofacitinib 11 mg + Methotrexate Placebo n=264 Participants Participants with low disease activity (LDA) at the end of open label phase were randomized to receive Tofacitinib MR 11 mg tablet once daily with matching placebo to blinded methotrexate at their previously stabilized dose for 24 weeks in double blind phase.	Double Blind: Tofacitinib 11mg + Methotrexate n=266 Participants Participants with LDA at the end of open label phase were randomized to receive Tofacitinib MR 11 mg tablet once daily with blinded methotrexate at their previously stabilized dose for 24 weeks in double blind phase.	Double Blind: Tofacitinib 11mg + Methotrexate Participants with LDA at the end of open label phase were randomized to receive Tofacitinib MR 11 mg tablet once daily with blinded methotrexate at their previously stabilized dose for 24 weeks in double blind phase.
Double Blind Phase: Percentage of Participants Achieving an American College of Rheumatology 20 Percent (%) (ACR20) Response at Weeks 36 and 48 Week 36	73.86 percentage of participants	80.83 percentage of participants	—
Double Blind Phase: Percentage of Participants Achieving an American College of Rheumatology 20 Percent (%) (ACR20) Response at Weeks 36 and 48 Week 48	73.11 percentage of participants	79.70 percentage of participants	—

SECONDARY outcome

Timeframe: Baseline (Day 1), Weeks 36 and 48

Population: FAS-DB included all participants who received at least 1 dose of investigational drug during the OL phase, were randomized and received at least 1 dose of the randomized investigational drug regimen during DB phase. NRI method was used to impute missing data.

Participants with 50% improvement in tender and swollen joint counts and 50% improvement in at least 3 of the 5 measures: PtGA, PhyGA, participant's assessment of arthritis pain, HAQ-DI and CRP. PtGA: participant assessed health on VAS, 0 mm (very well) to 100 mm (worst health condition), higher scores = worse condition. PhyGA: physician judged participants' pain on VAS, 0 (no pain) to 100 mm (extreme pain), higher scores = more pain. Participant's assessment of arthritis pain: participant assessed pain on VAS, 0 mm (no pain) to 100 mm (most severe pain), higher score = more pain. HAQ-DI: functional disability evaluation, score: 0 (no difficulty) to 3 (extreme difficulty), higher score implied more disability. The improvement was relative to baseline (Day 1).

Outcome measures

Measure	Double Blind: Tofacitinib 11 mg + Methotrexate Placebo n=264 Participants Participants with low disease activity (LDA) at the end of open label phase were randomized to receive Tofacitinib MR 11 mg tablet once daily with matching placebo to blinded methotrexate at their previously stabilized dose for 24 weeks in double blind phase.	Double Blind: Tofacitinib 11mg + Methotrexate n=266 Participants Participants with LDA at the end of open label phase were randomized to receive Tofacitinib MR 11 mg tablet once daily with blinded methotrexate at their previously stabilized dose for 24 weeks in double blind phase.	Double Blind: Tofacitinib 11mg + Methotrexate Participants with LDA at the end of open label phase were randomized to receive Tofacitinib MR 11 mg tablet once daily with blinded methotrexate at their previously stabilized dose for 24 weeks in double blind phase.
Double Blind Phase: Percentage of Participants Achieving an American College of Rheumatology 50% (ACR50) Response at Weeks 36 and 48 Week 36	53.79 percentage of participants	66.54 percentage of participants	—
Double Blind Phase: Percentage of Participants Achieving an American College of Rheumatology 50% (ACR50) Response at Weeks 36 and 48 Week 48	55.30 percentage of participants	67.29 percentage of participants	—

SECONDARY outcome

Timeframe: Baseline (Day 1), Weeks 36 and 48

Population: FAS-DB included all participants who received at least 1 dose of investigational drug during the OL phase, were randomized and received at least 1 dose of the randomized investigational drug regimen during DB phase. NRI method was used to impute missing data.

Participants with 70% improvement in tender and swollen joint counts and 70% improvement in at least 3 of the 5 measures: PtGA, PhyGA, participant's assessment of arthritis pain, HAQ-DI and CRP. PtGA: participant assessed health on VAS, 0 mm (very well) to 100 mm (worst health condition), higher scores = worse condition. PhyGA: physician judged participants' pain on VAS, 0 (no pain) to 100 mm (extreme pain), higher scores = more pain. Participant's assessment of arthritis pain: participant assessed pain on VAS, 0 mm (no pain) to 100 mm (most severe pain), higher score = more pain. HAQ-DI: functional disability evaluation, score: 0 (no difficulty) to 3 (extreme difficulty), higher score implied more disability. The improvement was relative to baseline (Day 1).

Outcome measures

Measure	Double Blind: Tofacitinib 11 mg + Methotrexate Placebo n=264 Participants Participants with low disease activity (LDA) at the end of open label phase were randomized to receive Tofacitinib MR 11 mg tablet once daily with matching placebo to blinded methotrexate at their previously stabilized dose for 24 weeks in double blind phase.	Double Blind: Tofacitinib 11mg + Methotrexate n=266 Participants Participants with LDA at the end of open label phase were randomized to receive Tofacitinib MR 11 mg tablet once daily with blinded methotrexate at their previously stabilized dose for 24 weeks in double blind phase.	Double Blind: Tofacitinib 11mg + Methotrexate Participants with LDA at the end of open label phase were randomized to receive Tofacitinib MR 11 mg tablet once daily with blinded methotrexate at their previously stabilized dose for 24 weeks in double blind phase.
Double Blind Phase: Percentage of Participants Achieving an American College of Rheumatology 70% (ACR70) Response at Weeks 36 and 48 Week 36	35.61 percentage of participants	40.98 percentage of participants	—
Double Blind Phase: Percentage of Participants Achieving an American College of Rheumatology 70% (ACR70) Response at Weeks 36 and 48 Week 48	37.88 percentage of participants	42.86 percentage of participants	—

SECONDARY outcome

Timeframe: Randomization (last non-missing measurement on or prior to the first dosing date in DB phase at Week 24), Weeks 36 and 48

Population: FAS-DB was analyzed. Here, 'Number analyzed' = Participants evaluable for this outcome measure at specified time points.

HAQ-DI assesses the degree of difficulty a participant has experienced during the past week in 8 domains of daily living activities: dressing/grooming; arising; eating; walking; reach; grip; hygiene; and other activities.. There were total of 30 items distributed in these 8 domains. Each item was scored on a 4-point scale from 0 to 3: 0= no difficulty; 1= some difficulty; 2= much difficulty; 3= unable to do. Overall score was computed as the sum of domain scores and divided by the number of domains answered. Total possible score range 0 (least difficulty) and 3 (extreme difficulty), where higher scores indicate more difficulty while performing daily living activities.

Outcome measures

Measure	Double Blind: Tofacitinib 11 mg + Methotrexate Placebo n=264 Participants Participants with low disease activity (LDA) at the end of open label phase were randomized to receive Tofacitinib MR 11 mg tablet once daily with matching placebo to blinded methotrexate at their previously stabilized dose for 24 weeks in double blind phase.	Double Blind: Tofacitinib 11mg + Methotrexate n=266 Participants Participants with LDA at the end of open label phase were randomized to receive Tofacitinib MR 11 mg tablet once daily with blinded methotrexate at their previously stabilized dose for 24 weeks in double blind phase.	Double Blind: Tofacitinib 11mg + Methotrexate Participants with LDA at the end of open label phase were randomized to receive Tofacitinib MR 11 mg tablet once daily with blinded methotrexate at their previously stabilized dose for 24 weeks in double blind phase.
Double Blind Phase: Change From Randomization in Health Assessment Questionnaire-Disability Index (HAQ-DI) at Weeks 36 and 48 Change at Week 36	0.10 units on a scale Standard Error 0.03	0.01 units on a scale Standard Error 0.03	—
Double Blind Phase: Change From Randomization in Health Assessment Questionnaire-Disability Index (HAQ-DI) at Weeks 36 and 48 Change at Week 48	0.01 units on a scale Standard Error 0.03	0.00 units on a scale Standard Error 0.03	—

SECONDARY outcome

Timeframe: Randomization (last non-missing measurement on or prior to the first dosing date in DB phase at Week 24), Weeks 36 and 48

Population: FAS-DB was analyzed. Here, 'Number analyzed' = Participants evaluable for this outcome measure at specified time points.

SF-36 is a participant reported standardized survey designed to assess generic health related quality of life. It consisted of 36 items evaluating 8 aspects of functional health and well-being: physical functioning, role physical, bodily pain, social functioning, mental health, role emotional, vitality, and general health perception. The score range for each of the 8 health aspects was from 0 (poor health) to 100 (better health), higher scores indicating good health condition. Scores of 8 health aspects were summarized to derive the 2 component scores (physical component scores [PCS], mental component scores [MCS]) ranging from 0 (worst) to 100 (best), where higher PCS/MCS indicated good health condition.

Outcome measures

Measure	Double Blind: Tofacitinib 11 mg + Methotrexate Placebo n=264 Participants Participants with low disease activity (LDA) at the end of open label phase were randomized to receive Tofacitinib MR 11 mg tablet once daily with matching placebo to blinded methotrexate at their previously stabilized dose for 24 weeks in double blind phase.	Double Blind: Tofacitinib 11mg + Methotrexate n=266 Participants Participants with LDA at the end of open label phase were randomized to receive Tofacitinib MR 11 mg tablet once daily with blinded methotrexate at their previously stabilized dose for 24 weeks in double blind phase.	Double Blind: Tofacitinib 11mg + Methotrexate Participants with LDA at the end of open label phase were randomized to receive Tofacitinib MR 11 mg tablet once daily with blinded methotrexate at their previously stabilized dose for 24 weeks in double blind phase.
Double Blind Phase: Change From Randomization in the Short Form 36 (SF-36) Health Survey 8 Domain Scores at Weeks 36 and 48 Change at Week 36: Mental Health Score	-1.22 units on a scale Standard Error 0.51	-0.32 units on a scale Standard Error 0.50	—
Double Blind Phase: Change From Randomization in the Short Form 36 (SF-36) Health Survey 8 Domain Scores at Weeks 36 and 48 Change at Week 36: Physical Functioning	-1.32 units on a scale Standard Error 0.50	-0.88 units on a scale Standard Error 0.49	—
Double Blind Phase: Change From Randomization in the Short Form 36 (SF-36) Health Survey 8 Domain Scores at Weeks 36 and 48 Change at Week 36: Role Physical Score	-1.69 units on a scale Standard Error 0.48	-0.02 units on a scale Standard Error 0.47	—
Double Blind Phase: Change From Randomization in the Short Form 36 (SF-36) Health Survey 8 Domain Scores at Weeks 36 and 48 Change at Week 36: Social Functioning	-0.98 units on a scale Standard Error 0.50	-0.84 units on a scale Standard Error 0.49	—
Double Blind Phase: Change From Randomization in the Short Form 36 (SF-36) Health Survey 8 Domain Scores at Weeks 36 and 48 Change at Week 36: Bodily Pain Score	-2.03 units on a scale Standard Error 0.53	-0.58 units on a scale Standard Error 0.52	—
Double Blind Phase: Change From Randomization in the Short Form 36 (SF-36) Health Survey 8 Domain Scores at Weeks 36 and 48 Change at Week 36: Role Emotional Score	-1.80 units on a scale Standard Error 0.56	-0.69 units on a scale Standard Error 0.55	—
Double Blind Phase: Change From Randomization in the Short Form 36 (SF-36) Health Survey 8 Domain Scores at Weeks 36 and 48 Change at Week 36: Vitality Score	-1.30 units on a scale Standard Error 0.50	-0.15 units on a scale Standard Error 0.50	—
Double Blind Phase: Change From Randomization in the Short Form 36 (SF-36) Health Survey 8 Domain Scores at Weeks 36 and 48 Change at Week 36: General Health Perception Score	-0.98 units on a scale Standard Error 0.44	-0.87 units on a scale Standard Error 0.43	—
Double Blind Phase: Change From Randomization in the Short Form 36 (SF-36) Health Survey 8 Domain Scores at Weeks 36 and 48 Change at Week 48: Physical Functioning	-0.46 units on a scale Standard Error 0.49	-0.97 units on a scale Standard Error 0.48	—
Double Blind Phase: Change From Randomization in the Short Form 36 (SF-36) Health Survey 8 Domain Scores at Weeks 36 and 48 Change at Week 48: Role Physical Score	-0.88 units on a scale Standard Error 0.51	-0.15 units on a scale Standard Error 0.50	—
Double Blind Phase: Change From Randomization in the Short Form 36 (SF-36) Health Survey 8 Domain Scores at Weeks 36 and 48 Change at Week 48: Social Functioning	-1.06 units on a scale Standard Error 0.53	-0.55 units on a scale Standard Error 0.52	—
Double Blind Phase: Change From Randomization in the Short Form 36 (SF-36) Health Survey 8 Domain Scores at Weeks 36 and 48 Change at Week 48: Bodily Pain Score	-1.46 units on a scale Standard Error 0.54	-0.71 units on a scale Standard Error 0.54	—
Double Blind Phase: Change From Randomization in the Short Form 36 (SF-36) Health Survey 8 Domain Scores at Weeks 36 and 48 Change at Week 48: Mental Health Score	-0.34 units on a scale Standard Error 0.54	0.12 units on a scale Standard Error 0.54	—
Double Blind Phase: Change From Randomization in the Short Form 36 (SF-36) Health Survey 8 Domain Scores at Weeks 36 and 48 Change at Week 48: Role Emotional Score	-0.83 units on a scale Standard Error 0.54	-0.36 units on a scale Standard Error 0.54	—
Double Blind Phase: Change From Randomization in the Short Form 36 (SF-36) Health Survey 8 Domain Scores at Weeks 36 and 48 Change at Week 48: Vitality Score	-0.77 units on a scale Standard Error 0.52	-0.25 units on a scale Standard Error 0.52	—
Double Blind Phase: Change From Randomization in the Short Form 36 (SF-36) Health Survey 8 Domain Scores at Weeks 36 and 48 Change at Week 48: General Health Perception Score	-0.43 units on a scale Standard Error 0.45	-1.05 units on a scale Standard Error 0.44	—

SECONDARY outcome

Timeframe: Randomization (last non-missing measurement on or prior to the first dosing date in DB phase at Week 24), Weeks 36 and 48

Population: FAS-DB was analyzed. Here, 'Number analyzed' = Participants evaluable for this outcome measure at specified time points.

SF-36 is a participant reported standardized survey designed to assess generic health related quality of life. It consisted of 36 items evaluating 8 aspects of functional health and well-being: physical functioning, role physical, bodily pain, social functioning, mental health, role emotional, vitality, and general health perception. The score range for each of the 8 health aspects was from 0 (poor health) to 100 (better health), higher scores indicating good health condition. Scores of 8 health aspects were summarized aggregated to derive the two 2 component scores PCS and MCS ranging from 0 (worst) to 100 (best), where higher PCS/MCS indicated good health condition.

Outcome measures

Measure	Double Blind: Tofacitinib 11 mg + Methotrexate Placebo n=264 Participants Participants with low disease activity (LDA) at the end of open label phase were randomized to receive Tofacitinib MR 11 mg tablet once daily with matching placebo to blinded methotrexate at their previously stabilized dose for 24 weeks in double blind phase.	Double Blind: Tofacitinib 11mg + Methotrexate n=266 Participants Participants with LDA at the end of open label phase were randomized to receive Tofacitinib MR 11 mg tablet once daily with blinded methotrexate at their previously stabilized dose for 24 weeks in double blind phase.	Double Blind: Tofacitinib 11mg + Methotrexate Participants with LDA at the end of open label phase were randomized to receive Tofacitinib MR 11 mg tablet once daily with blinded methotrexate at their previously stabilized dose for 24 weeks in double blind phase.
Double Blind Phase: Change From Randomization in the SF-36 Health Survey Component Scores at Weeks 36 and 48 Change at Week 36: Physical Component Score	-1.42 units on a scale Standard Error 0.44	-0.60 units on a scale Standard Error 0.43	—
Double Blind Phase: Change From Randomization in the SF-36 Health Survey Component Scores at Weeks 36 and 48 Change at Week 36: Mental Component Score	-1.25 units on a scale Standard Error 0.48	-0.43 units on a scale Standard Error 0.47	—
Double Blind Phase: Change From Randomization in the SF-36 Health Survey Component Scores at Weeks 36 and 48 Change at Week 48: Physical Component Score	-0.83 units on a scale Standard Error 0.44	-0.92 units on a scale Standard Error 0.43	—
Double Blind Phase: Change From Randomization in the SF-36 Health Survey Component Scores at Weeks 36 and 48 Change at Week 48: Mental Component Score	-0.65 units on a scale Standard Error 0.51	0.03 units on a scale Standard Error 0.50	—

SECONDARY outcome

Timeframe: Randomization (last non-missing measurement on or prior to the first dosing date in DB phase at Week 24), Week 36 and 48

Population: FAS-DB was analyzed. Here, 'Number analyzed' = Participants evaluable for this outcome measure at specified time point.

WPAI is 6-question participant rated questionnaire to determine the impact of rheumatoid arthritis and yields 4 types of outcomes: absenteeism (work time missed), presenteeism (impairment while working), work productivity loss (overall work impairment), and daily activity impairment (activity impairment) for a period of 7 days prior to a visit. These 4 outcomes are expressed as an impairment percentage (range from 0 to 100), with higher numbers indicating greater impairment and less productivity.

Outcome measures

Measure	Double Blind: Tofacitinib 11 mg + Methotrexate Placebo n=264 Participants Participants with low disease activity (LDA) at the end of open label phase were randomized to receive Tofacitinib MR 11 mg tablet once daily with matching placebo to blinded methotrexate at their previously stabilized dose for 24 weeks in double blind phase.	Double Blind: Tofacitinib 11mg + Methotrexate n=266 Participants Participants with LDA at the end of open label phase were randomized to receive Tofacitinib MR 11 mg tablet once daily with blinded methotrexate at their previously stabilized dose for 24 weeks in double blind phase.	Double Blind: Tofacitinib 11mg + Methotrexate Participants with LDA at the end of open label phase were randomized to receive Tofacitinib MR 11 mg tablet once daily with blinded methotrexate at their previously stabilized dose for 24 weeks in double blind phase.
Double Blind Phase: Change From Randomization in the Work Productivity and Activity Impairment (WPAI) Scores at Week 36 and 48 Change at Week 36: Presenteeism	3.68 percentage impairment Standard Error 2.20	0.67 percentage impairment Standard Error 2.07	—
Double Blind Phase: Change From Randomization in the Work Productivity and Activity Impairment (WPAI) Scores at Week 36 and 48 Change at Week 36: Absenteeism	-1.39 percentage impairment Standard Error 1.79	-3.00 percentage impairment Standard Error 1.69	—
Double Blind Phase: Change From Randomization in the Work Productivity and Activity Impairment (WPAI) Scores at Week 36 and 48 Change at Week 36: Daily activity impairment	4.00 percentage impairment Standard Error 1.35	0.81 percentage impairment Standard Error 1.34	—
Double Blind Phase: Change From Randomization in the Work Productivity and Activity Impairment (WPAI) Scores at Week 36 and 48 Change at Week 36: Work productivity loss	3.03 percentage impairment Standard Error 2.57	0.19 percentage impairment Standard Error 2.41	—
Double Blind Phase: Change From Randomization in the Work Productivity and Activity Impairment (WPAI) Scores at Week 36 and 48 Change at Week 48: Absenteeism	-2.21 percentage impairment Standard Error 1.70	-1.69 percentage impairment Standard Error 1.61	—
Double Blind Phase: Change From Randomization in the Work Productivity and Activity Impairment (WPAI) Scores at Week 36 and 48 Change at Week 48: Daily activity impairment	2.86 percentage impairment Standard Error 1.47	1.25 percentage impairment Standard Error 1.46	—
Double Blind Phase: Change From Randomization in the Work Productivity and Activity Impairment (WPAI) Scores at Week 36 and 48 Change at Week 48: Presenteeism	2.82 percentage impairment Standard Error 2.78	3.72 percentage impairment Standard Error 2.61	—
Double Blind Phase: Change From Randomization in the Work Productivity and Activity Impairment (WPAI) Scores at Week 36 and 48 Change at Week 48: Work productivity loss	2.98 percentage impairment Standard Error 3.09	5.45 percentage impairment Standard Error 2.91	—

SECONDARY outcome

Timeframe: Randomization (last non-missing measurement on or prior to the first dosing date in DB phase at Week 24), Weeks 36 and 48

Population: FAS-DB population was analyzed. Here, 'Number analyzed' = Participants evaluable for this outcome measure for specified time points.

EQ-5D was a participant completed instrument designed to assess impact on quality of life in terms of a single utility score in 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression. 3 possible answers for mobility: 1=no problem in walking, 2=moderate problems in walking, 3= confined to bed; self-care: 1=no problem, 2=moderate problems, 3= unable to wash/dress; usual activities: 1=no problem, 2=moderate problems, 3= unable to do usual activities; pain and discomfort: 1=no pain or discomfort, 2=moderate pain or discomfort, 3= extreme pain or discomfort; anxiety and depression: 1=not anxious or depressed, 2=moderately anxious or depressed, 3= extremely anxious or depressed. The 5-dimensional systems are converted into a single index utility score between 0 and 1, where higher score indicated a better health state.

Outcome measures

Measure	Double Blind: Tofacitinib 11 mg + Methotrexate Placebo n=264 Participants Participants with low disease activity (LDA) at the end of open label phase were randomized to receive Tofacitinib MR 11 mg tablet once daily with matching placebo to blinded methotrexate at their previously stabilized dose for 24 weeks in double blind phase.	Double Blind: Tofacitinib 11mg + Methotrexate n=266 Participants Participants with LDA at the end of open label phase were randomized to receive Tofacitinib MR 11 mg tablet once daily with blinded methotrexate at their previously stabilized dose for 24 weeks in double blind phase.	Double Blind: Tofacitinib 11mg + Methotrexate Participants with LDA at the end of open label phase were randomized to receive Tofacitinib MR 11 mg tablet once daily with blinded methotrexate at their previously stabilized dose for 24 weeks in double blind phase.
Double Blind Phase: Change From Randomization in the European Quality of Life - 5 Dimensions Questionnaire (EQ-5D) Scores at Weeks 36 and 48 Change at Week 36	-0.05 units on a scale Standard Error 0.01	-0.01 units on a scale Standard Error 0.01	—
Double Blind Phase: Change From Randomization in the European Quality of Life - 5 Dimensions Questionnaire (EQ-5D) Scores at Weeks 36 and 48 Change at Week 48	-0.02 units on a scale Standard Error 0.01	0.00 units on a scale Standard Error 0.01	—

SECONDARY outcome

Timeframe: Randomization (last non-missing measurement on or prior to the first dosing date in DB phase at Week 24), Weeks 36 and 48

Population: FAS-DB population was analyzed. Here, 'Number analyzed' = Participants evaluable for this outcome measure for specified time points.

The FACIT-Fatigue scale was a participant completed questionnaire consisted of 13 items that assessed fatigue. Each item was scored on a scale of 0 (maximum fatigue) to 4 (no fatigue), higher scores indicate less fatigue. Total FACIT-fatigue score was obtained by addition of scores from 13 items, giving a possible overall range from 0 (maximum fatigue) to 52 (no fatigue). Higher FACIT-fatigue scores indicated lower level of fatigue, better participant status.

Outcome measures

Measure	Double Blind: Tofacitinib 11 mg + Methotrexate Placebo n=264 Participants Participants with low disease activity (LDA) at the end of open label phase were randomized to receive Tofacitinib MR 11 mg tablet once daily with matching placebo to blinded methotrexate at their previously stabilized dose for 24 weeks in double blind phase.	Double Blind: Tofacitinib 11mg + Methotrexate n=266 Participants Participants with LDA at the end of open label phase were randomized to receive Tofacitinib MR 11 mg tablet once daily with blinded methotrexate at their previously stabilized dose for 24 weeks in double blind phase.	Double Blind: Tofacitinib 11mg + Methotrexate Participants with LDA at the end of open label phase were randomized to receive Tofacitinib MR 11 mg tablet once daily with blinded methotrexate at their previously stabilized dose for 24 weeks in double blind phase.
Double Blind Phase: Change From Randomization in the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scale Scores at Weeks 36 and 48 Change at Week 36	-0.99 units on a scale Standard Error 0.43	-0.80 units on a scale Standard Error 0.43	—
Double Blind Phase: Change From Randomization in the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scale Scores at Weeks 36 and 48 Change at Week 48	-0.34 units on a scale Standard Error 0.46	-0.52 units on a scale Standard Error 0.45	—

SECONDARY outcome

Timeframe: Baseline (Day 1), Weeks 36 and 48

Population: FAS-DB population was analyzed. Here, 'Number analyzed' = Participants evaluable for this outcome measure at specified time points. NRI method was used to impute missing data.

HAQ-DI assesses the degree of difficulty a participant has experienced during the past week in 8 domains of daily living activities: dressing/grooming; arising; eating; walking; reach; grip; hygiene; and other activities.. There were total of 30 items distributed in these 8 domains. Each item was scored on a 4-point scale from 0 to 3: 0= no difficulty; 1= some difficulty; 2= much difficulty; 3= unable to do. Overall score was computed as the sum of domain scores and divided by the number of domains answered. Total possible score range 0 (least difficulty) and 3 (extreme difficulty), where higher scores indicate more difficulty while performing daily living activities. Percentage of participants with an improvement of at least 0.22 units in HAQ scores from baseline (Day 1) to Weeks 36 and 48 were reported in this outcome measure.

Outcome measures

Measure	Double Blind: Tofacitinib 11 mg + Methotrexate Placebo n=264 Participants Participants with low disease activity (LDA) at the end of open label phase were randomized to receive Tofacitinib MR 11 mg tablet once daily with matching placebo to blinded methotrexate at their previously stabilized dose for 24 weeks in double blind phase.	Double Blind: Tofacitinib 11mg + Methotrexate n=266 Participants Participants with LDA at the end of open label phase were randomized to receive Tofacitinib MR 11 mg tablet once daily with blinded methotrexate at their previously stabilized dose for 24 weeks in double blind phase.	Double Blind: Tofacitinib 11mg + Methotrexate Participants with LDA at the end of open label phase were randomized to receive Tofacitinib MR 11 mg tablet once daily with blinded methotrexate at their previously stabilized dose for 24 weeks in double blind phase.
Double Blind Phase: Percentage of Participants Achieving an Improvement of at Least 0.22 Units in HAQ-DI at Weeks 36 and 48 Week 36	67.05 percentage of participants	77.07 percentage of participants	—
Double Blind Phase: Percentage of Participants Achieving an Improvement of at Least 0.22 Units in HAQ-DI at Weeks 36 and 48 Week 48	68.56 percentage of participants	75.19 percentage of participants	—

OTHER_PRE_SPECIFIED outcome

Timeframe: For OL Phase: Baseline up to Week 24; For DB Phase: Week 24 up to Week 52 (up to 28 days after last dose)

Population: Overall study safety analysis set included all participants who received at least one dose of study drug during the study.

An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent were events between first dose of study drug and up to Week 52 (up to 28 days after last dose) that were absent before treatment or that worsened relative to pretreatment state. AEs included both serious and non-serious AEs.

Outcome measures

Measure	Double Blind: Tofacitinib 11 mg + Methotrexate Placebo n=694 Participants Participants with low disease activity (LDA) at the end of open label phase were randomized to receive Tofacitinib MR 11 mg tablet once daily with matching placebo to blinded methotrexate at their previously stabilized dose for 24 weeks in double blind phase.	Double Blind: Tofacitinib 11mg + Methotrexate n=264 Participants Participants with LDA at the end of open label phase were randomized to receive Tofacitinib MR 11 mg tablet once daily with blinded methotrexate at their previously stabilized dose for 24 weeks in double blind phase.	Double Blind: Tofacitinib 11mg + Methotrexate n=266 Participants Participants with LDA at the end of open label phase were randomized to receive Tofacitinib MR 11 mg tablet once daily with blinded methotrexate at their previously stabilized dose for 24 weeks in double blind phase.
Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious AEs SAEs	20 Participants	10 Participants	5 Participants
Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious AEs AEs	362 Participants	107 Participants	109 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: For OL Phase: Baseline up to Week 24; For DB Phase: Week 24 up to Week 48

Population: Overall study safety analysis Set included all participants who received at least one dose of study drug during the study. Overall number of participants analyzed=participants evaluable for this outcome measure.

Abnormality criteria: Hemoglobin (Hb),Hematocrit,Erythrocytes(Ery): <0.8*LLN;Ery. Mean corpuscular volume <0.9*lower limit of normal (LLN), >1.1*upper limit of normal (ULN); Platelets:<0.5*LLN,>1.75*ULN;WBCs:<0.6*LLN,>1.5*ULN; Lymphocytes/WBCs, Neutrophils/WBCs:<0.8*LLN,>1.2* ULN;Basophils,Basophils/WBCs,Eosinophils,Eosinophils/WBCs,Monocytes, Monocytes/WBCs: >1.2*ULN;Prothrombin Time, Prothrombin Intl. Normalized Ratio:>1.1*ULN; ESR:>1.5*ULN; Bilirubin,Direct Bilirubin,Indirect Bilirubin: >1.5*ULN; Aspartate Aminotransferase (AT),Alanine AT,Gamma Glutamyl Transferase,Alkaline Phosphatase:>3.0*ULN; Protein, Albumin: <0.8*LLN, >1.2x ULN; Blood Urea Nitrogen, Creatinine, Triglycerides: >1.3*ULN;HDL Cholesterol:<0.8*LLN;Sodium <0.95*LLN, >1.05*ULN;Potassium, Chloride, Calcium, Bicarbonate: <0.9*LLN, >1.1*ULN; Glucose: <0.6*LLN, >1.5*ULN; Creatine Kinase: >2.0*ULN; Cholesterol:>1.3*ULN;Specific Gravity:<1.003;pH:<4.5; urine glucose,Ketones,urine protein,urine Hb,WBCs Esterase: >=1.

Outcome measures

Measure	Double Blind: Tofacitinib 11 mg + Methotrexate Placebo n=688 Participants Participants with low disease activity (LDA) at the end of open label phase were randomized to receive Tofacitinib MR 11 mg tablet once daily with matching placebo to blinded methotrexate at their previously stabilized dose for 24 weeks in double blind phase.	Double Blind: Tofacitinib 11mg + Methotrexate n=263 Participants Participants with LDA at the end of open label phase were randomized to receive Tofacitinib MR 11 mg tablet once daily with blinded methotrexate at their previously stabilized dose for 24 weeks in double blind phase.	Double Blind: Tofacitinib 11mg + Methotrexate n=263 Participants Participants with LDA at the end of open label phase were randomized to receive Tofacitinib MR 11 mg tablet once daily with blinded methotrexate at their previously stabilized dose for 24 weeks in double blind phase.
Number of Participants With Abnormal Laboratory Parameters	682 Participants	263 Participants	263 Participants

Adverse Events

Open Label: Tofacitinib 11 mg + Methotrexate

Serious events: 20 serious events

Other events: 158 other events

Deaths: 0 deaths

Double Blind: Tofacitinib 11 mg + Methotrexate Placebo

Serious events: 10 serious events

Other events: 24 other events

Deaths: 0 deaths

Double Blind: Tofacitinib 11mg + Methotrexate

Serious events: 5 serious events

Other events: 31 other events

Deaths: 2 deaths

Serious adverse events

Measure	Open Label: Tofacitinib 11 mg + Methotrexate n=694 participants at risk Participants with moderate to severe rheumatoid arthritis (RA) and who were insufficiently responding to their stable dose of methotrexate treatment previous to enrollment in this study, received Tofacitinib modified release (MR) 11 milligram (mg) tablet once daily (QD) with methotrexate at their previous stable dose for 24 weeks in open label phase (OL).	Double Blind: Tofacitinib 11 mg + Methotrexate Placebo n=264 participants at risk Participants with low disease activity (LDA) at the end of open label phase were randomized to receive Tofacitinib MR 11 mg tablet once daily with matching placebo to blinded methotrexate at their previously stabilized dose for 24 weeks in double blind phase.	Double Blind: Tofacitinib 11mg + Methotrexate n=266 participants at risk Participants with LDA at the end of open label phase were randomized to receive Tofacitinib MR 11 mg tablet once daily with blinded methotrexate at their previously stabilized dose for 24 weeks in double blind phase.
Gastrointestinal disorders Umbilical hernia	0.00% 0/694 • Baseline (Day 1) up to Week 52 Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. AEs were evaluated for participants with at least 1 dose of the study drug during the study.	0.38% 1/264 • Baseline (Day 1) up to Week 52 Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. AEs were evaluated for participants with at least 1 dose of the study drug during the study.	0.00% 0/266 • Baseline (Day 1) up to Week 52 Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. AEs were evaluated for participants with at least 1 dose of the study drug during the study.
Infections and infestations Encephalitis viral	0.00% 0/694 • Baseline (Day 1) up to Week 52 Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. AEs were evaluated for participants with at least 1 dose of the study drug during the study.	0.00% 0/264 • Baseline (Day 1) up to Week 52 Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. AEs were evaluated for participants with at least 1 dose of the study drug during the study.	0.38% 1/266 • Baseline (Day 1) up to Week 52 Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. AEs were evaluated for participants with at least 1 dose of the study drug during the study.
Infections and infestations Infective exacerbation of chronic obstructive airways disease	0.00% 0/694 • Baseline (Day 1) up to Week 52 Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. AEs were evaluated for participants with at least 1 dose of the study drug during the study.	0.00% 0/264 • Baseline (Day 1) up to Week 52 Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. AEs were evaluated for participants with at least 1 dose of the study drug during the study.	0.38% 1/266 • Baseline (Day 1) up to Week 52 Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. AEs were evaluated for participants with at least 1 dose of the study drug during the study.
Infections and infestations Osteomyelitis	0.00% 0/694 • Baseline (Day 1) up to Week 52 Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. AEs were evaluated for participants with at least 1 dose of the study drug during the study.	0.38% 1/264 • Baseline (Day 1) up to Week 52 Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. AEs were evaluated for participants with at least 1 dose of the study drug during the study.	0.00% 0/266 • Baseline (Day 1) up to Week 52 Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. AEs were evaluated for participants with at least 1 dose of the study drug during the study.
Infections and infestations Pneumonia	0.43% 3/694 • Baseline (Day 1) up to Week 52 Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. AEs were evaluated for participants with at least 1 dose of the study drug during the study.	0.38% 1/264 • Baseline (Day 1) up to Week 52 Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. AEs were evaluated for participants with at least 1 dose of the study drug during the study.	0.00% 0/266 • Baseline (Day 1) up to Week 52 Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. AEs were evaluated for participants with at least 1 dose of the study drug during the study.
Injury, poisoning and procedural complications Femur fracture	0.14% 1/694 • Baseline (Day 1) up to Week 52 Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. AEs were evaluated for participants with at least 1 dose of the study drug during the study.	0.38% 1/264 • Baseline (Day 1) up to Week 52 Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. AEs were evaluated for participants with at least 1 dose of the study drug during the study.	0.00% 0/266 • Baseline (Day 1) up to Week 52 Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. AEs were evaluated for participants with at least 1 dose of the study drug during the study.
Injury, poisoning and procedural complications Spinal compression fracture	0.00% 0/694 • Baseline (Day 1) up to Week 52 Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. AEs were evaluated for participants with at least 1 dose of the study drug during the study.	0.38% 1/264 • Baseline (Day 1) up to Week 52 Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. AEs were evaluated for participants with at least 1 dose of the study drug during the study.	0.00% 0/266 • Baseline (Day 1) up to Week 52 Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. AEs were evaluated for participants with at least 1 dose of the study drug during the study.
Musculoskeletal and connective tissue disorders Mobility decreased	0.00% 0/694 • Baseline (Day 1) up to Week 52 Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. AEs were evaluated for participants with at least 1 dose of the study drug during the study.	0.38% 1/264 • Baseline (Day 1) up to Week 52 Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. AEs were evaluated for participants with at least 1 dose of the study drug during the study.	0.00% 0/266 • Baseline (Day 1) up to Week 52 Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. AEs were evaluated for participants with at least 1 dose of the study drug during the study.
Musculoskeletal and connective tissue disorders Osteoarthritis	0.00% 0/694 • Baseline (Day 1) up to Week 52 Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. AEs were evaluated for participants with at least 1 dose of the study drug during the study.	0.00% 0/264 • Baseline (Day 1) up to Week 52 Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. AEs were evaluated for participants with at least 1 dose of the study drug during the study.	0.38% 1/266 • Baseline (Day 1) up to Week 52 Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. AEs were evaluated for participants with at least 1 dose of the study drug during the study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Adrenal adenoma	0.00% 0/694 • Baseline (Day 1) up to Week 52 Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. AEs were evaluated for participants with at least 1 dose of the study drug during the study.	0.38% 1/264 • Baseline (Day 1) up to Week 52 Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. AEs were evaluated for participants with at least 1 dose of the study drug during the study.	0.00% 0/266 • Baseline (Day 1) up to Week 52 Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. AEs were evaluated for participants with at least 1 dose of the study drug during the study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Glioblastoma	0.00% 0/694 • Baseline (Day 1) up to Week 52 Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. AEs were evaluated for participants with at least 1 dose of the study drug during the study.	0.38% 1/264 • Baseline (Day 1) up to Week 52 Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. AEs were evaluated for participants with at least 1 dose of the study drug during the study.	0.00% 0/266 • Baseline (Day 1) up to Week 52 Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. AEs were evaluated for participants with at least 1 dose of the study drug during the study.
Nervous system disorders Nerve root compression	0.00% 0/694 • Baseline (Day 1) up to Week 52 Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. AEs were evaluated for participants with at least 1 dose of the study drug during the study.	0.38% 1/264 • Baseline (Day 1) up to Week 52 Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. AEs were evaluated for participants with at least 1 dose of the study drug during the study.	0.00% 0/266 • Baseline (Day 1) up to Week 52 Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. AEs were evaluated for participants with at least 1 dose of the study drug during the study.
Renal and urinary disorders Renal colic	0.00% 0/694 • Baseline (Day 1) up to Week 52 Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. AEs were evaluated for participants with at least 1 dose of the study drug during the study.	0.38% 1/264 • Baseline (Day 1) up to Week 52 Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. AEs were evaluated for participants with at least 1 dose of the study drug during the study.	0.00% 0/266 • Baseline (Day 1) up to Week 52 Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. AEs were evaluated for participants with at least 1 dose of the study drug during the study.
Respiratory, thoracic and mediastinal disorders Asthma	0.14% 1/694 • Baseline (Day 1) up to Week 52 Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. AEs were evaluated for participants with at least 1 dose of the study drug during the study.	0.38% 1/264 • Baseline (Day 1) up to Week 52 Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. AEs were evaluated for participants with at least 1 dose of the study drug during the study.	0.00% 0/266 • Baseline (Day 1) up to Week 52 Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. AEs were evaluated for participants with at least 1 dose of the study drug during the study.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.00% 0/694 • Baseline (Day 1) up to Week 52 Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. AEs were evaluated for participants with at least 1 dose of the study drug during the study.	0.38% 1/264 • Baseline (Day 1) up to Week 52 Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. AEs were evaluated for participants with at least 1 dose of the study drug during the study.	0.75% 2/266 • Baseline (Day 1) up to Week 52 Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. AEs were evaluated for participants with at least 1 dose of the study drug during the study.
Cardiac disorders Angina unstable	0.14% 1/694 • Baseline (Day 1) up to Week 52 Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. AEs were evaluated for participants with at least 1 dose of the study drug during the study.	0.00% 0/264 • Baseline (Day 1) up to Week 52 Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. AEs were evaluated for participants with at least 1 dose of the study drug during the study.	0.00% 0/266 • Baseline (Day 1) up to Week 52 Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. AEs were evaluated for participants with at least 1 dose of the study drug during the study.
Cardiac disorders Atrial fibrillation	0.14% 1/694 • Baseline (Day 1) up to Week 52 Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. AEs were evaluated for participants with at least 1 dose of the study drug during the study.	0.00% 0/264 • Baseline (Day 1) up to Week 52 Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. AEs were evaluated for participants with at least 1 dose of the study drug during the study.	0.00% 0/266 • Baseline (Day 1) up to Week 52 Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. AEs were evaluated for participants with at least 1 dose of the study drug during the study.
Gastrointestinal disorders Hiatus hernia	0.14% 1/694 • Baseline (Day 1) up to Week 52 Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. AEs were evaluated for participants with at least 1 dose of the study drug during the study.	0.00% 0/264 • Baseline (Day 1) up to Week 52 Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. AEs were evaluated for participants with at least 1 dose of the study drug during the study.	0.00% 0/266 • Baseline (Day 1) up to Week 52 Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. AEs were evaluated for participants with at least 1 dose of the study drug during the study.
Gastrointestinal disorders Pancreatitis acute	0.14% 1/694 • Baseline (Day 1) up to Week 52 Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. AEs were evaluated for participants with at least 1 dose of the study drug during the study.	0.00% 0/264 • Baseline (Day 1) up to Week 52 Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. AEs were evaluated for participants with at least 1 dose of the study drug during the study.	0.00% 0/266 • Baseline (Day 1) up to Week 52 Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. AEs were evaluated for participants with at least 1 dose of the study drug during the study.
Gastrointestinal disorders Peritoneal disorder	0.14% 1/694 • Baseline (Day 1) up to Week 52 Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. AEs were evaluated for participants with at least 1 dose of the study drug during the study.	0.00% 0/264 • Baseline (Day 1) up to Week 52 Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. AEs were evaluated for participants with at least 1 dose of the study drug during the study.	0.00% 0/266 • Baseline (Day 1) up to Week 52 Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. AEs were evaluated for participants with at least 1 dose of the study drug during the study.
Hepatobiliary disorders Bile duct stone	0.14% 1/694 • Baseline (Day 1) up to Week 52 Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. AEs were evaluated for participants with at least 1 dose of the study drug during the study.	0.00% 0/264 • Baseline (Day 1) up to Week 52 Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. AEs were evaluated for participants with at least 1 dose of the study drug during the study.	0.00% 0/266 • Baseline (Day 1) up to Week 52 Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. AEs were evaluated for participants with at least 1 dose of the study drug during the study.
Hepatobiliary disorders Gallbladder disorder	0.14% 1/694 • Baseline (Day 1) up to Week 52 Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. AEs were evaluated for participants with at least 1 dose of the study drug during the study.	0.00% 0/264 • Baseline (Day 1) up to Week 52 Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. AEs were evaluated for participants with at least 1 dose of the study drug during the study.	0.00% 0/266 • Baseline (Day 1) up to Week 52 Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. AEs were evaluated for participants with at least 1 dose of the study drug during the study.
Infections and infestations Influenza	0.14% 1/694 • Baseline (Day 1) up to Week 52 Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. AEs were evaluated for participants with at least 1 dose of the study drug during the study.	0.00% 0/264 • Baseline (Day 1) up to Week 52 Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. AEs were evaluated for participants with at least 1 dose of the study drug during the study.	0.00% 0/266 • Baseline (Day 1) up to Week 52 Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. AEs were evaluated for participants with at least 1 dose of the study drug during the study.
Infections and infestations Respiratory tract infection	0.14% 1/694 • Baseline (Day 1) up to Week 52 Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. AEs were evaluated for participants with at least 1 dose of the study drug during the study.	0.00% 0/264 • Baseline (Day 1) up to Week 52 Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. AEs were evaluated for participants with at least 1 dose of the study drug during the study.	0.00% 0/266 • Baseline (Day 1) up to Week 52 Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. AEs were evaluated for participants with at least 1 dose of the study drug during the study.
Injury, poisoning and procedural complications Fall	0.14% 1/694 • Baseline (Day 1) up to Week 52 Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. AEs were evaluated for participants with at least 1 dose of the study drug during the study.	0.00% 0/264 • Baseline (Day 1) up to Week 52 Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. AEs were evaluated for participants with at least 1 dose of the study drug during the study.	0.00% 0/266 • Baseline (Day 1) up to Week 52 Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. AEs were evaluated for participants with at least 1 dose of the study drug during the study.
Injury, poisoning and procedural complications Hip fracture	0.14% 1/694 • Baseline (Day 1) up to Week 52 Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. AEs were evaluated for participants with at least 1 dose of the study drug during the study.	0.00% 0/264 • Baseline (Day 1) up to Week 52 Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. AEs were evaluated for participants with at least 1 dose of the study drug during the study.	0.00% 0/266 • Baseline (Day 1) up to Week 52 Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. AEs were evaluated for participants with at least 1 dose of the study drug during the study.
Injury, poisoning and procedural complications Patella fracture	0.14% 1/694 • Baseline (Day 1) up to Week 52 Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. AEs were evaluated for participants with at least 1 dose of the study drug during the study.	0.00% 0/264 • Baseline (Day 1) up to Week 52 Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. AEs were evaluated for participants with at least 1 dose of the study drug during the study.	0.00% 0/266 • Baseline (Day 1) up to Week 52 Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. AEs were evaluated for participants with at least 1 dose of the study drug during the study.
Injury, poisoning and procedural complications Tibia fracture	0.14% 1/694 • Baseline (Day 1) up to Week 52 Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. AEs were evaluated for participants with at least 1 dose of the study drug during the study.	0.00% 0/264 • Baseline (Day 1) up to Week 52 Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. AEs were evaluated for participants with at least 1 dose of the study drug during the study.	0.00% 0/266 • Baseline (Day 1) up to Week 52 Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. AEs were evaluated for participants with at least 1 dose of the study drug during the study.
Investigations Blood pressure increased	0.14% 1/694 • Baseline (Day 1) up to Week 52 Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. AEs were evaluated for participants with at least 1 dose of the study drug during the study.	0.00% 0/264 • Baseline (Day 1) up to Week 52 Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. AEs were evaluated for participants with at least 1 dose of the study drug during the study.	0.00% 0/266 • Baseline (Day 1) up to Week 52 Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. AEs were evaluated for participants with at least 1 dose of the study drug during the study.
Metabolism and nutrition disorders Dehydration	0.14% 1/694 • Baseline (Day 1) up to Week 52 Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. AEs were evaluated for participants with at least 1 dose of the study drug during the study.	0.00% 0/264 • Baseline (Day 1) up to Week 52 Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. AEs were evaluated for participants with at least 1 dose of the study drug during the study.	0.00% 0/266 • Baseline (Day 1) up to Week 52 Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. AEs were evaluated for participants with at least 1 dose of the study drug during the study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Papillary thyroid cancer	0.14% 1/694 • Baseline (Day 1) up to Week 52 Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. AEs were evaluated for participants with at least 1 dose of the study drug during the study.	0.00% 0/264 • Baseline (Day 1) up to Week 52 Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. AEs were evaluated for participants with at least 1 dose of the study drug during the study.	0.00% 0/266 • Baseline (Day 1) up to Week 52 Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. AEs were evaluated for participants with at least 1 dose of the study drug during the study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostate cancer	0.14% 1/694 • Baseline (Day 1) up to Week 52 Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. AEs were evaluated for participants with at least 1 dose of the study drug during the study.	0.00% 0/264 • Baseline (Day 1) up to Week 52 Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. AEs were evaluated for participants with at least 1 dose of the study drug during the study.	0.00% 0/266 • Baseline (Day 1) up to Week 52 Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. AEs were evaluated for participants with at least 1 dose of the study drug during the study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Thyroid cancer metastatic	0.14% 1/694 • Baseline (Day 1) up to Week 52 Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. AEs were evaluated for participants with at least 1 dose of the study drug during the study.	0.00% 0/264 • Baseline (Day 1) up to Week 52 Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. AEs were evaluated for participants with at least 1 dose of the study drug during the study.	0.00% 0/266 • Baseline (Day 1) up to Week 52 Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. AEs were evaluated for participants with at least 1 dose of the study drug during the study.
Renal and urinary disorders Nephrolithiasis	0.14% 1/694 • Baseline (Day 1) up to Week 52 Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. AEs were evaluated for participants with at least 1 dose of the study drug during the study.	0.00% 0/264 • Baseline (Day 1) up to Week 52 Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. AEs were evaluated for participants with at least 1 dose of the study drug during the study.	0.00% 0/266 • Baseline (Day 1) up to Week 52 Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. AEs were evaluated for participants with at least 1 dose of the study drug during the study.
Reproductive system and breast disorders Cervical dysplasia	0.14% 1/694 • Baseline (Day 1) up to Week 52 Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. AEs were evaluated for participants with at least 1 dose of the study drug during the study.	0.00% 0/264 • Baseline (Day 1) up to Week 52 Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. AEs were evaluated for participants with at least 1 dose of the study drug during the study.	0.00% 0/266 • Baseline (Day 1) up to Week 52 Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. AEs were evaluated for participants with at least 1 dose of the study drug during the study.
Respiratory, thoracic and mediastinal disorders Bronchitis chronic	0.14% 1/694 • Baseline (Day 1) up to Week 52 Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. AEs were evaluated for participants with at least 1 dose of the study drug during the study.	0.00% 0/264 • Baseline (Day 1) up to Week 52 Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. AEs were evaluated for participants with at least 1 dose of the study drug during the study.	0.00% 0/266 • Baseline (Day 1) up to Week 52 Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. AEs were evaluated for participants with at least 1 dose of the study drug during the study.
Respiratory, thoracic and mediastinal disorders Interstitial lung disease	0.14% 1/694 • Baseline (Day 1) up to Week 52 Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. AEs were evaluated for participants with at least 1 dose of the study drug during the study.	0.00% 0/264 • Baseline (Day 1) up to Week 52 Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. AEs were evaluated for participants with at least 1 dose of the study drug during the study.	0.00% 0/266 • Baseline (Day 1) up to Week 52 Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. AEs were evaluated for participants with at least 1 dose of the study drug during the study.

Other adverse events

Measure	Open Label: Tofacitinib 11 mg + Methotrexate n=694 participants at risk Participants with moderate to severe rheumatoid arthritis (RA) and who were insufficiently responding to their stable dose of methotrexate treatment previous to enrollment in this study, received Tofacitinib modified release (MR) 11 milligram (mg) tablet once daily (QD) with methotrexate at their previous stable dose for 24 weeks in open label phase (OL).	Double Blind: Tofacitinib 11 mg + Methotrexate Placebo n=264 participants at risk Participants with low disease activity (LDA) at the end of open label phase were randomized to receive Tofacitinib MR 11 mg tablet once daily with matching placebo to blinded methotrexate at their previously stabilized dose for 24 weeks in double blind phase.	Double Blind: Tofacitinib 11mg + Methotrexate n=266 participants at risk Participants with LDA at the end of open label phase were randomized to receive Tofacitinib MR 11 mg tablet once daily with blinded methotrexate at their previously stabilized dose for 24 weeks in double blind phase.
Infections and infestations Bronchitis	0.00% 0/694 • Baseline (Day 1) up to Week 52 Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. AEs were evaluated for participants with at least 1 dose of the study drug during the study.	1.1% 3/264 • Baseline (Day 1) up to Week 52 Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. AEs were evaluated for participants with at least 1 dose of the study drug during the study.	2.6% 7/266 • Baseline (Day 1) up to Week 52 Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. AEs were evaluated for participants with at least 1 dose of the study drug during the study.
Infections and infestations Nasopharyngitis	5.0% 35/694 • Baseline (Day 1) up to Week 52 Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. AEs were evaluated for participants with at least 1 dose of the study drug during the study.	1.9% 5/264 • Baseline (Day 1) up to Week 52 Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. AEs were evaluated for participants with at least 1 dose of the study drug during the study.	2.6% 7/266 • Baseline (Day 1) up to Week 52 Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. AEs were evaluated for participants with at least 1 dose of the study drug during the study.
Infections and infestations Upper respiratory tract infection	4.8% 33/694 • Baseline (Day 1) up to Week 52 Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. AEs were evaluated for participants with at least 1 dose of the study drug during the study.	1.5% 4/264 • Baseline (Day 1) up to Week 52 Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. AEs were evaluated for participants with at least 1 dose of the study drug during the study.	2.3% 6/266 • Baseline (Day 1) up to Week 52 Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. AEs were evaluated for participants with at least 1 dose of the study drug during the study.
Investigations Alanine aminotransferase increased	2.3% 16/694 • Baseline (Day 1) up to Week 52 Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. AEs were evaluated for participants with at least 1 dose of the study drug during the study.	1.9% 5/264 • Baseline (Day 1) up to Week 52 Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. AEs were evaluated for participants with at least 1 dose of the study drug during the study.	3.8% 10/266 • Baseline (Day 1) up to Week 52 Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. AEs were evaluated for participants with at least 1 dose of the study drug during the study.
Investigations Aspartate aminotransferase increased	0.00% 0/694 • Baseline (Day 1) up to Week 52 Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. AEs were evaluated for participants with at least 1 dose of the study drug during the study.	1.9% 5/264 • Baseline (Day 1) up to Week 52 Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. AEs were evaluated for participants with at least 1 dose of the study drug during the study.	2.3% 6/266 • Baseline (Day 1) up to Week 52 Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. AEs were evaluated for participants with at least 1 dose of the study drug during the study.
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/694 • Baseline (Day 1) up to Week 52 Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. AEs were evaluated for participants with at least 1 dose of the study drug during the study.	2.7% 7/264 • Baseline (Day 1) up to Week 52 Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. AEs were evaluated for participants with at least 1 dose of the study drug during the study.	0.75% 2/266 • Baseline (Day 1) up to Week 52 Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. AEs were evaluated for participants with at least 1 dose of the study drug during the study.
Gastrointestinal disorders Diarrhoea	2.3% 16/694 • Baseline (Day 1) up to Week 52 Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. AEs were evaluated for participants with at least 1 dose of the study drug during the study.	0.00% 0/264 • Baseline (Day 1) up to Week 52 Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. AEs were evaluated for participants with at least 1 dose of the study drug during the study.	0.00% 0/266 • Baseline (Day 1) up to Week 52 Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. AEs were evaluated for participants with at least 1 dose of the study drug during the study.
Gastrointestinal disorders Nausea	2.9% 20/694 • Baseline (Day 1) up to Week 52 Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. AEs were evaluated for participants with at least 1 dose of the study drug during the study.	0.00% 0/264 • Baseline (Day 1) up to Week 52 Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. AEs were evaluated for participants with at least 1 dose of the study drug during the study.	0.00% 0/266 • Baseline (Day 1) up to Week 52 Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. AEs were evaluated for participants with at least 1 dose of the study drug during the study.
Nervous system disorders Headache	2.4% 17/694 • Baseline (Day 1) up to Week 52 Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. AEs were evaluated for participants with at least 1 dose of the study drug during the study.	0.00% 0/264 • Baseline (Day 1) up to Week 52 Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. AEs were evaluated for participants with at least 1 dose of the study drug during the study.	0.00% 0/266 • Baseline (Day 1) up to Week 52 Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. AEs were evaluated for participants with at least 1 dose of the study drug during the study.
Nervous system disorders Dizziness	2.2% 15/694 • Baseline (Day 1) up to Week 52 Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. AEs were evaluated for participants with at least 1 dose of the study drug during the study.	0.00% 0/264 • Baseline (Day 1) up to Week 52 Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. AEs were evaluated for participants with at least 1 dose of the study drug during the study.	0.00% 0/266 • Baseline (Day 1) up to Week 52 Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. AEs were evaluated for participants with at least 1 dose of the study drug during the study.
Vascular disorders Hypertension	2.4% 17/694 • Baseline (Day 1) up to Week 52 Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. AEs were evaluated for participants with at least 1 dose of the study drug during the study.	0.00% 0/264 • Baseline (Day 1) up to Week 52 Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. AEs were evaluated for participants with at least 1 dose of the study drug during the study.	0.00% 0/266 • Baseline (Day 1) up to Week 52 Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. AEs were evaluated for participants with at least 1 dose of the study drug during the study.
Infections and infestations Urinary tract infection	2.7% 19/694 • Baseline (Day 1) up to Week 52 Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. AEs were evaluated for participants with at least 1 dose of the study drug during the study.	0.00% 0/264 • Baseline (Day 1) up to Week 52 Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. AEs were evaluated for participants with at least 1 dose of the study drug during the study.	0.00% 0/266 • Baseline (Day 1) up to Week 52 Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. AEs were evaluated for participants with at least 1 dose of the study drug during the study.

Additional Information

Pfizer ClinicalTrials.gov Call Center

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Phone: 1-800-718-1021

Email: ClinicalTrials.gov_Inquiries@pfizer.com

Results disclosure agreements

• Principal investigator is a sponsor employee Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
• Publication restrictions are in place

Restriction type: OTHER