Trial Outcomes & Findings for A Study To Evaluate The Safety And Efficacy Of Tofacitinib Modified Release Tablets Compared To Tofacitinib Immediate Release Tablets In Adult Patients With Rheumatoid Arthritis (NCT NCT02281552)

Results Overview

DAS28 is a measure of disease activity in participants with rheumatoid arthritis. DAS28-4 (CRP) was calculated from swollen joint count (SJC) and tender/painful joint count (TJC) using 28 joints count, CRP (milligrams per liter \[mg/L\]) and patient global assessment of disease activity on a 100 millimeter (mm) visual analog scale (VAS: scores ranging from 0 mm \[very well\] to 100 mm \[extremely bad\], 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) \[less than or equal to\] \<= 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 (CRP) less than (\<) 2.6 implied remission.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

209 participants

Primary outcome timeframe

Baseline, Week 12

Results posted on

2018-10-12

Participant Flow

Participant milestones

Participant milestones
Measure	Tofacitinib Modified Release (MR) Participants orally received 11 milligrams (mg) of tofacitinib MR tablets once daily and matching placebo of tofacitinib IR tablets twice daily for 12 weeks.	Tofacitinib Immediate Release (IR) Participants orally received 5 mg of tofacitinib IR tablets twice daily and matching placebo of tofacitinib MR tablets once daily for 12 weeks.
Overall Study STARTED	104	105
Overall Study COMPLETED	100	95
Overall Study NOT COMPLETED	4	10

Reasons for withdrawal

Reasons for withdrawal
Measure	Tofacitinib Modified Release (MR) Participants orally received 11 milligrams (mg) of tofacitinib MR tablets once daily and matching placebo of tofacitinib IR tablets twice daily for 12 weeks.	Tofacitinib Immediate Release (IR) Participants orally received 5 mg of tofacitinib IR tablets twice daily and matching placebo of tofacitinib MR tablets once daily for 12 weeks.
Overall Study Medication error	1	0
Overall Study Insufficient clinical response	0	1
Overall Study Adverse Event	3	9

Baseline Characteristics

A Study To Evaluate The Safety And Efficacy Of Tofacitinib Modified Release Tablets Compared To Tofacitinib Immediate Release Tablets In Adult Patients With Rheumatoid Arthritis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Tofacitinib Modified Release (MR) n=104 Participants Participants orally received 11 mg of tofacitinib MR tablets once daily and matching placebo of tofacitinib IR tablets twice daily for 12 weeks.	Tofacitinib Immediate Release (IR) n=105 Participants Participants orally received 5 mg of tofacitinib IR tablets twice daily and matching placebo of tofacitinib MR tablets once daily for 12 weeks.	Total n=209 Participants Total of all reporting groups
Age, Continuous	57.1 years STANDARD_DEVIATION 11.4 • n=5 Participants	58.9 years STANDARD_DEVIATION 10.2 • n=7 Participants	58 years STANDARD_DEVIATION 10.8 • n=5 Participants
Sex: Female, Male Female	86 Participants n=5 Participants	75 Participants n=7 Participants	161 Participants n=5 Participants
Sex: Female, Male Male	18 Participants n=5 Participants	30 Participants n=7 Participants	48 Participants n=5 Participants
Race/Ethnicity, Customized Asian	104 Participants n=5 Participants	105 Participants n=7 Participants	209 Participants n=5 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized White	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline, Week 12

Population: Full analysis set (FAS) included all participants who were randomized and received at least one dose of the randomized investigational drug. Here, "N" (number of participants analyzed) signifies those participants who were evaluable for this specified outcome measure.

DAS28 is a measure of disease activity in participants with rheumatoid arthritis. DAS28-4 (CRP) was calculated from swollen joint count (SJC) and tender/painful joint count (TJC) using 28 joints count, CRP (milligrams per liter \[mg/L\]) and patient global assessment of disease activity on a 100 millimeter (mm) visual analog scale (VAS: scores ranging from 0 mm \[very well\] to 100 mm \[extremely bad\], 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) \[less than or equal to\] \<= 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 (CRP) less than (\<) 2.6 implied remission.

Outcome measures

Outcome measures
Measure	Tofacitinib Modified Release (MR) n=100 Participants Participants orally received 11 mg of tofacitinib MR tablets once daily and matching placebo of tofacitinib IR tablets twice daily for 12 weeks.	Tofacitinib Immediate Release (IR) n=95 Participants Participants orally received 5 mg of tofacitinib IR tablets twice daily and matching placebo of tofacitinib MR tablets once daily for 12 weeks.
Change From Baseline in Disease Activity Score in 28 Joints Using 4 Variables (DAS28-4) (C-Reactive Protein [CRP]) at Week 12	-2.43 units on a scale Standard Error 0.09	-2.85 units on a scale Standard Error 0.09

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: FAS included all participants who were randomized and received at least one dose of the randomized investigational drug. Here, "N" (number of participants analyzed) signifies those participants who were evaluable for this specified 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 (millimeters per hour \[mm/hr\]) and patient global assessment of disease activity on a 100 mm visual analog scale (VAS: scores ranging from 0 mm \[very well\] to 100 mm \[extremely bad\], 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.

Outcome measures

Outcome measures
Measure	Tofacitinib Modified Release (MR) n=99 Participants Participants orally received 11 mg of tofacitinib MR tablets once daily and matching placebo of tofacitinib IR tablets twice daily for 12 weeks.	Tofacitinib Immediate Release (IR) n=95 Participants Participants orally received 5 mg of tofacitinib IR tablets twice daily and matching placebo of tofacitinib MR tablets once daily for 12 weeks.
Change From Baseline in Disease Activity Score in 28 Joints Using 4 Variables (DAS28-4) (Erythrocyte Sedimentation Rate [ESR]) at Week 12	-2.50 units on a scale Standard Error 0.09	-2.86 units on a scale Standard Error 0.09

SECONDARY outcome

Timeframe: Week 12

Population: FAS included all participants who were randomized and received at least one dose of the randomized investigational drug. Here, "N" (number of participants analyzed) signifies those participants who were evaluable for this specified outcome measure. Missing values due to withdrawal were imputed using non-responder imputation (NRI) method.

Participants with 20% improvement in 68-tender and 66-swollen joint counts and 20% improvement in at least 3 of the 5 measures: patient's global assessment of arthritis, physician global assessment of arthritis, patient's assessment of arthritis pain, health assessment questionnaire-disability index(HAQ-DI) and CRP. Patient's global assessment of arthritis: participant assessed arthritis by 100 mm VAS, score: 0 mm (no arthritis) to 100 mm (extreme arthritis), higher score implied more arthritis. Physician global assessment of arthritis: physician judged participants arthritis by 100 mm VAS, score: 0 mm (no arthritis) to 100 mm (extreme arthritis), higher score implied more arthritis. Patient's assessment of arthritis pain: participant assessed arthritis pain by 100 mm VAS, score: 0 mm (no pain) to 100 mm (most severe pain), higher score implied more pain. HAQ-DI: functional disability evaluation, score: 0 (no difficulty) to 3 (extreme difficulty), higher score implied more disability.

Outcome measures

Outcome measures
Measure	Tofacitinib Modified Release (MR) n=103 Participants Participants orally received 11 mg of tofacitinib MR tablets once daily and matching placebo of tofacitinib IR tablets twice daily for 12 weeks.	Tofacitinib Immediate Release (IR) n=104 Participants Participants orally received 5 mg of tofacitinib IR tablets twice daily and matching placebo of tofacitinib MR tablets once daily for 12 weeks.
Number of Participants Achieving an American College of Rheumatology 20 Percent [%] (ACR20) Response at Week 12	87 participants	83 participants

SECONDARY outcome

Timeframe: Week 12

Population: FAS included all participants who were randomized and received at least one dose of the randomized investigational drug. Here, "N" (number of participants analyzed) signifies those participants who were evaluable for this specified outcome measure. Missing values due to withdrawal were imputed using NRI method.

Participants with 50% improvement in 68-tender and 66-swollen joint counts and 50% improvement in at least 3 of the 5 measures: patient's global assessment of arthritis, physician global assessment of arthritis, patient's assessment of arthritis pain, health assessment questionnaire-disability index(HAQ-DI) and CRP. Patient's global assessment of arthritis: participant assessed arthritis by 100 mm VAS, score: 0 mm (no arthritis) to 100 mm (extreme arthritis), higher score implied more arthritis. Physician global assessment of arthritis: physician judged participants arthritis by 100 mm VAS, score: 0 mm (no arthritis) to 100 mm (extreme arthritis), higher score implied more arthritis. Patient's assessment of arthritis pain: participant assessed arthritis pain by 100 mm VAS, score: 0 mm (no pain) to 100 mm (most severe pain), higher score implied more pain. HAQ-DI: functional disability evaluation, score: 0 (no difficulty) to 3 (extreme difficulty), higher score implied more disability.

Outcome measures

Outcome measures
Measure	Tofacitinib Modified Release (MR) n=103 Participants Participants orally received 11 mg of tofacitinib MR tablets once daily and matching placebo of tofacitinib IR tablets twice daily for 12 weeks.	Tofacitinib Immediate Release (IR) n=104 Participants Participants orally received 5 mg of tofacitinib IR tablets twice daily and matching placebo of tofacitinib MR tablets once daily for 12 weeks.
Number of Participants Achieving an American College of Rheumatology 50% (ACR50) Response at Week 12	70 participants	71 participants

SECONDARY outcome

Timeframe: Week 12

Population: FAS included all participants who were randomized and received at least one dose of the randomized investigational drug. Here, "N" (number of participants analyzed) signifies those participants who were evaluable for this specified outcome measure. Missing values due to withdrawal were imputed using NRI method.

Participants with 70% improvement in 68-tender and 66-swollen joint counts and 70% improvement in at least 3 of the 5 measures: patient's global assessment of arthritis, physician global assessment of arthritis, patient's assessment of arthritis pain, health assessment questionnaire-disability index(HAQ-DI) and CRP. Patient's global assessment of arthritis: participant assessed arthritis by 100 mm VAS, score: 0 mm (no arthritis) to 100 mm (extreme arthritis), higher score implied more arthritis. Physician global assessment of arthritis: physician judged participants arthritis by 100 mm VAS, score: 0 mm (no arthritis) to 100 mm (extreme arthritis), higher score implied more arthritis. Patient's assessment of arthritis pain: participant assessed arthritis pain by 100 mm VAS, score: 0 mm (no pain) to 100 mm (most severe pain), higher score implied more pain. HAQ-DI: functional disability evaluation, score: 0 (no difficulty) to 3 (extreme difficulty), higher score implied more disability.

Outcome measures

Outcome measures
Measure	Tofacitinib Modified Release (MR) n=103 Participants Participants orally received 11 mg of tofacitinib MR tablets once daily and matching placebo of tofacitinib IR tablets twice daily for 12 weeks.	Tofacitinib Immediate Release (IR) n=104 Participants Participants orally received 5 mg of tofacitinib IR tablets twice daily and matching placebo of tofacitinib MR tablets once daily for 12 weeks.
Number of Participants Achieving an American College of Rheumatology 70% (ACR70) Response at Week 12	32 participants	48 participants

SECONDARY outcome

Timeframe: Week 12

Population: FAS included all participants who were randomized and received at least one dose of the randomized investigational drug. Here, "N" (number of participants analyzed) signifies those participants who were evaluable for this specified outcome measure. Missing values due to withdrawal were imputed using NRI method.

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 patient global assessment of disease activity on a 100 mm visual analog scale (VAS: scores ranging from 0 mm \[very well\] to 100 mm \[extremely bad\], 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. Number of participants with DAS remission (DAS28-4-CRP\<2.6) were reported in this outcome measure.

Outcome measures

Outcome measures
Measure	Tofacitinib Modified Release (MR) n=103 Participants Participants orally received 11 mg of tofacitinib MR tablets once daily and matching placebo of tofacitinib IR tablets twice daily for 12 weeks.	Tofacitinib Immediate Release (IR) n=104 Participants Participants orally received 5 mg of tofacitinib IR tablets twice daily and matching placebo of tofacitinib MR tablets once daily for 12 weeks.
Number of Participants With DAS Remission (DAS28-4-CRP <2.6) at Week 12	52 participants	72 participants

SECONDARY outcome

Timeframe: Week 12

Population: FAS included all participants who were randomized and received at least one dose of the randomized investigational drug. Here, "N" (number of participants analyzed) signifies those participants who were evaluable for this specified outcome measure. Missing values due to withdrawal were imputed using NRI method.

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 patient global assessment of disease activity on a 100 mm visual analog scale (VAS: scores ranging from 0 mm \[very well\] to 100 mm \[extremely bad\], 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. Number of participants with DAS remission (DAS28-4-ESR\<2.6) were reported in this outcome measure.

Outcome measures

Outcome measures
Measure	Tofacitinib Modified Release (MR) n=103 Participants Participants orally received 11 mg of tofacitinib MR tablets once daily and matching placebo of tofacitinib IR tablets twice daily for 12 weeks.	Tofacitinib Immediate Release (IR) n=104 Participants Participants orally received 5 mg of tofacitinib IR tablets twice daily and matching placebo of tofacitinib MR tablets once daily for 12 weeks.
Number of Participants With DAS Remission (DAS28-4-ESR <2.6) at Week 12	18 participants	36 participants

SECONDARY outcome

Timeframe: Week 12

Population: FAS included all participants who were randomized and received at least one dose of the randomized investigational drug. Here, "N" (number of participants analyzed) signifies those participants who were evaluable for this specified outcome measure. Missing values due to withdrawal were imputed using NRI method.

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 patient global assessment of disease activity on a 100 mm visual analog scale (VAS: scores ranging from 0 mm \[very well\] to 100 mm \[extremely bad\], 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. Number of participants with low disease activity (DAS28-4-CRP\<=3.2) were reported in this outcome measure.

Outcome measures

Outcome measures
Measure	Tofacitinib Modified Release (MR) n=103 Participants Participants orally received 11 mg of tofacitinib MR tablets once daily and matching placebo of tofacitinib IR tablets twice daily for 12 weeks.	Tofacitinib Immediate Release (IR) n=104 Participants Participants orally received 5 mg of tofacitinib IR tablets twice daily and matching placebo of tofacitinib MR tablets once daily for 12 weeks.
Number of Participants With Low Disease Activity (DAS28-4-CRP <=3.2) at Week 12	76 participants	82 participants

SECONDARY outcome

Timeframe: Week 12

Population: FAS included all participants who were randomized and received at least one dose of the randomized investigational drug. Here, "N" (number of participants analyzed) signifies those participants who were evaluable for this specified outcome measure. Missing values due to withdrawal were imputed using NRI method.

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 patient global assessment of disease activity on a 100 mm visual analog scale (VAS: scores ranging from 0 mm \[very well\] to 100 mm \[extremely bad\], 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. Number of participants with low disease activity (DAS28-4-ESR\<=3.2) were reported in this outcome measure.

Outcome measures

Outcome measures
Measure	Tofacitinib Modified Release (MR) n=103 Participants Participants orally received 11 mg of tofacitinib MR tablets once daily and matching placebo of tofacitinib IR tablets twice daily for 12 weeks.	Tofacitinib Immediate Release (IR) n=104 Participants Participants orally received 5 mg of tofacitinib IR tablets twice daily and matching placebo of tofacitinib MR tablets once daily for 12 weeks.
Number of Participants With Low Disease Activity (DAS28-4-ESR <=3.2) at Week 12	44 participants	63 participants

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: FAS included all participants who were randomized and received at least one dose of the randomized investigational drug. Here, "N" (number of participants analyzed) signifies those participants who were evaluable for this specified outcome measure.

HAQ-DI assesses the degree of difficulty a participant has experienced during the past week in 8 categories of daily living activities: dressing/grooming; arising; eating; walking; reach; grip; hygiene; and other activities over past week. Each activity category consisted of 2-3 items. Each item scored on 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

Outcome measures
Measure	Tofacitinib Modified Release (MR) n=99 Participants Participants orally received 11 mg of tofacitinib MR tablets once daily and matching placebo of tofacitinib IR tablets twice daily for 12 weeks.	Tofacitinib Immediate Release (IR) n=95 Participants Participants orally received 5 mg of tofacitinib IR tablets twice daily and matching placebo of tofacitinib MR tablets once daily for 12 weeks.
Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) at Week 12	-0.44 units on a scale Standard Error 0.04	-0.46 units on a scale Standard Error 0.04

SECONDARY outcome

Timeframe: Week 12

Population: FAS included all participants who were randomized and received at least one dose of the randomized investigational drug. Here, "N" (number of participants analyzed) signifies those participants who were evaluable for this specified outcome measure. Missing values due to withdrawal were imputed using NRI method.

HAQ-DI assesses the degree of difficulty a participant has experienced during the past week in 8 categories of daily living activities: dressing/grooming; arising; eating; walking; reach; grip; hygiene; and other activities over past week. Each activity category consisted of 2-3 items. Each item scored on 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. Number of participants with an improvement of at least 0.22 units in HAQ scores from baseline to Week 12 were reported in this outcome measure.

Outcome measures

Outcome measures
Measure	Tofacitinib Modified Release (MR) n=103 Participants Participants orally received 11 mg of tofacitinib MR tablets once daily and matching placebo of tofacitinib IR tablets twice daily for 12 weeks.	Tofacitinib Immediate Release (IR) n=104 Participants Participants orally received 5 mg of tofacitinib IR tablets twice daily and matching placebo of tofacitinib MR tablets once daily for 12 weeks.
Number of Participants Achieving an Improvement of at Least 0.22 Units in Health Assessment Questionnaire (HAQ Scores) at Week 12	65 participants	60 participants

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: FAS included all participants who were randomized and received at least one dose of the randomized investigational drug. Here, "N" (number of participants analyzed) signifies those participants who were evaluable for this specified outcome measure.

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. 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 aggregated to derive the two component scores (physical component scores \[PCS\], mental component scores \[MCS\]) ranging from 0 (worst) to 100 (best), where higher scores indicated good health condition.

Outcome measures

Outcome measures
Measure	Tofacitinib Modified Release (MR) n=99 Participants Participants orally received 11 mg of tofacitinib MR tablets once daily and matching placebo of tofacitinib IR tablets twice daily for 12 weeks.	Tofacitinib Immediate Release (IR) n=95 Participants Participants orally received 5 mg of tofacitinib IR tablets twice daily and matching placebo of tofacitinib MR tablets once daily for 12 weeks.
Change From Baseline in the Short Form 36 (SF-36) Health Survey Domain Scores at Week 12 Vitality	8.07 units on a scale Standard Error 0.75	8.20 units on a scale Standard Error 0.76
Change From Baseline in the Short Form 36 (SF-36) Health Survey Domain Scores at Week 12 Physical Functioning	5.54 units on a scale Standard Error 0.67	6.29 units on a scale Standard Error 0.68
Change From Baseline in the Short Form 36 (SF-36) Health Survey Domain Scores at Week 12 Role Physical	6.51 units on a scale Standard Error 0.81	6.97 units on a scale Standard Error 0.83
Change From Baseline in the Short Form 36 (SF-36) Health Survey Domain Scores at Week 12 Bodily Pain	9.41 units on a scale Standard Error 0.77	11.92 units on a scale Standard Error 0.78
Change From Baseline in the Short Form 36 (SF-36) Health Survey Domain Scores at Week 12 General Health	4.53 units on a scale Standard Error 0.52	4.72 units on a scale Standard Error 0.53
Change From Baseline in the Short Form 36 (SF-36) Health Survey Domain Scores at Week 12 Social Function	4.26 units on a scale Standard Error 0.63	5.06 units on a scale Standard Error 0.64
Change From Baseline in the Short Form 36 (SF-36) Health Survey Domain Scores at Week 12 Role Emotional	7.23 units on a scale Standard Error 0.86	6.56 units on a scale Standard Error 0.87
Change From Baseline in the Short Form 36 (SF-36) Health Survey Domain Scores at Week 12 Mental Health	4.46 units on a scale Standard Error 0.80	5.26 units on a scale Standard Error 0.81

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: FAS included all participants who were randomized and received at least one dose of the randomized investigational drug. Here, "N" (number of participants analyzed) signifies those participants who were evaluable for this specified outcome measure.

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. 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 aggregated to derive the two component scores PCS and MCS ranging from 0 (worst) to 100 (best), where higher scores indicated good health condition.

Outcome measures

Outcome measures
Measure	Tofacitinib Modified Release (MR) n=99 Participants Participants orally received 11 mg of tofacitinib MR tablets once daily and matching placebo of tofacitinib IR tablets twice daily for 12 weeks.	Tofacitinib Immediate Release (IR) n=95 Participants Participants orally received 5 mg of tofacitinib IR tablets twice daily and matching placebo of tofacitinib MR tablets once daily for 12 weeks.
Change From Baseline in the Short Form 36 (SF-36) Health Survey Component Scores at Week 12 PCS	6.59 units on a scale Standard Error 0.58	7.85 units on a scale Standard Error 0.59
Change From Baseline in the Short Form 36 (SF-36) Health Survey Component Scores at Week 12 MCS	5.29 units on a scale Standard Error 0.76	5.08 units on a scale Standard Error 0.77

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: FAS included all participants who were randomized and received at least one dose of the randomized investigational drug. Here, "N" (number of participants analyzed) signifies those participants who were evaluable for this specified outcome measure.

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 (not at all) to 4 (very much), Total score ranging from 0 (not at all) to 52 (very much), higher scores represented lower level of fatigue.

Outcome measures

Outcome measures
Measure	Tofacitinib Modified Release (MR) n=99 Participants Participants orally received 11 mg of tofacitinib MR tablets once daily and matching placebo of tofacitinib IR tablets twice daily for 12 weeks.	Tofacitinib Immediate Release (IR) n=95 Participants Participants orally received 5 mg of tofacitinib IR tablets twice daily and matching placebo of tofacitinib MR tablets once daily for 12 weeks.
Change From Baseline in the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scale Scores at Week 12	5.28 units on a scale Standard Error 0.66	6.12 units on a scale Standard Error 0.67

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: FAS included all participants who were randomized and received at least one dose of the randomized investigational drug. Here, "N" (number of participants analyzed) signifies those participants who were evaluable for this specified outcome measure.

EQ-5D was a participant completed instrument designed to assess impact on quality of life in terms of a single utility score in five domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression with 3 possible answers for each item (1=no problem, 2=moderate problems, 3=severe problems). 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

Outcome measures
Measure	Tofacitinib Modified Release (MR) n=99 Participants Participants orally received 11 mg of tofacitinib MR tablets once daily and matching placebo of tofacitinib IR tablets twice daily for 12 weeks.	Tofacitinib Immediate Release (IR) n=95 Participants Participants orally received 5 mg of tofacitinib IR tablets twice daily and matching placebo of tofacitinib MR tablets once daily for 12 weeks.
Change From Baseline in the European Quality of Life - 5 Dimensions Questionnaire (EQ-5D) Scores at Week 12	0.20 units on a scale Standard Error 0.02	0.25 units on a scale Standard Error 0.02

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline up to 12 weeks

Population: Safety analysis set included all participants who were randomized and received at least one dose of the randomized investigational drug.

An Adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An 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 AEs were events between first dose of study drug and up to 12 weeks that were absent before treatment or that worsened relative to pretreatment state. AEs included both serious and non- serious adverse events.

Outcome measures

Outcome measures
Measure	Tofacitinib Modified Release (MR) n=104 Participants Participants orally received 11 mg of tofacitinib MR tablets once daily and matching placebo of tofacitinib IR tablets twice daily for 12 weeks.	Tofacitinib Immediate Release (IR) n=105 Participants Participants orally received 5 mg of tofacitinib IR tablets twice daily and matching placebo of tofacitinib MR tablets once daily for 12 weeks.
Number of Participants With Treatment- Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) AEs	55 participants	54 participants
Number of Participants With Treatment- Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) SAEs	5 participants	4 participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline up to 12 weeks

Population: Safety analysis set included all participants who were randomized and received at least one dose of the randomized investigational drug.

Criteria: lipids(cholesterol\[CH\] milligrams/deciliter\[mg/dL\] \>1.3\*upper limit normal(ULN), high-density lipoprotein CH mg/dL \<0.8\*lower limit normal(LLN), Low-density lipoprotein CH mg/dL \>1.2\* ULN, triglycerides mg/dL \>1.3\*ULN); neutrophil count(NC) \<1000 cells/cubic milliliters(mm\^3), platelet counts(PC) \<100,000 P/mm\^3, lymphocyte counts(LC) \<500 L/mm\^3, any single (aspartate transaminase elevation(ASTE)/alanine transaminase elevation(ALTE) \>=3\*ULN, hemoglobin(Hb) value \<8.0 grams(g)/dL or \>=2 g/dL below baseline, any serum creatinine(SC) increase(inc) \>50% or inc \>0.5 mg/dL over the average of screening(OAS) and baseline values(BV), 2 sequential ASTE/ALTE\>=3\*ULN with total bilirubin value(TBV) \>=2\*ULN, ASTE/ALTE \>=3\*ULN, ASTE/ALTE \>=5\*ULN, Hb \<8.0 g/dL or decrease of \>30% from BV, PC \<75,000 P/mm\^3, NC \<1000 cells/mm\^3, LC \<500 L/mm\^3, confirmed inc in SC \>50% OAS and BV and detection of hepatitis B virus-deoxyribonucleic acid(HBV-DNA) by the two sequential quantitative tests.

Outcome measures

Outcome measures
Measure	Tofacitinib Modified Release (MR) n=104 Participants Participants orally received 11 mg of tofacitinib MR tablets once daily and matching placebo of tofacitinib IR tablets twice daily for 12 weeks.	Tofacitinib Immediate Release (IR) n=105 Participants Participants orally received 5 mg of tofacitinib IR tablets twice daily and matching placebo of tofacitinib MR tablets once daily for 12 weeks.
Number of Participants With Clinically Significant Laboratory Test Abnormalities 2sequential Hb<8.0 g/dL or decrease of >30%from BV	0 participants	1 participants
Number of Participants With Clinically Significant Laboratory Test Abnormalities 2 sequential lymphocyte count <500 lymphocytes/mm3	0 participants	0 participants
Number of Participants With Clinically Significant Laboratory Test Abnormalities Cholesterol	11 participants	8 participants
Number of Participants With Clinically Significant Laboratory Test Abnormalities High-density lipoprotein Cholesterol	1 participants	1 participants
Number of Participants With Clinically Significant Laboratory Test Abnormalities Low-density lipoprotein Cholesterol	22 participants	21 participants
Number of Participants With Clinically Significant Laboratory Test Abnormalities Triglycerides	6 participants	10 participants
Number of Participants With Clinically Significant Laboratory Test Abnormalities Neutrophil counts <1000 cells/mm3	0 participants	0 participants
Number of Participants With Clinically Significant Laboratory Test Abnormalities Platelet counts <100,000 platelets/mm3	0 participants	0 participants
Number of Participants With Clinically Significant Laboratory Test Abnormalities Lymphocyte counts <500 lymphocytes/mm3	1 participants	0 participants
Number of Participants With Clinically Significant Laboratory Test Abnormalities Any single AST and/or ALT elevation >=3xULN	1 participants	0 participants
Number of Participants With Clinically Significant Laboratory Test Abnormalities Any single Hb value <8.0 g/dL or >=2 gm/dL	0 participants	2 participants
Number of Participants With Clinically Significant Laboratory Test Abnormalities Any serum creatinine increase >50%	0 participants	0 participants
Number of Participants With Clinically Significant Laboratory Test Abnormalities 2sequential AST/ALT elevations>=3xULN, TBV>=2xULN	0 participants	0 participants
Number of Participants With Clinically Significant Laboratory Test Abnormalities 2 sequential AST or ALT elevations >=3xULN	1 participants	0 participants
Number of Participants With Clinically Significant Laboratory Test Abnormalities 2 sequential AST or ALT elevations >=5xULN	0 participants	0 participants
Number of Participants With Clinically Significant Laboratory Test Abnormalities 2 sequential platelet counts <75,000 platelets/mm3	0 participants	0 participants
Number of Participants With Clinically Significant Laboratory Test Abnormalities 2 sequential neutrophil counts <1000 cells/mm3	0 participants	0 participants
Number of Participants With Clinically Significant Laboratory Test Abnormalities Confirmed increases in serum creatinine >50%	0 participants	0 participants
Number of Participants With Clinically Significant Laboratory Test Abnormalities Detection of HBV-DNA	0 participants	0 participants

Adverse Events

Tofacitinib Modified Release (MR)

Serious events: 5 serious events

Other events: 10 other events

Deaths: 0 deaths

Tofacitinib Immediate Release (IR)

Serious events: 4 serious events

Other events: 13 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Tofacitinib Modified Release (MR) n=104 participants at risk Participants orally received 11 mg of tofacitinib MR tablets once daily and matching placebo of tofacitinib IR tablets twice daily for 12 weeks.	Tofacitinib Immediate Release (IR) n=105 participants at risk Participants orally received 5 mg of tofacitinib IR tablets twice daily and matching placebo of tofacitinib MR tablets once daily for 12 weeks.
Blood and lymphatic system disorders Anaemia	0.00% 0/104 • From baseline up to 12 weeks Same event may appear as AE and serious AE, what is presented are distinct events. Event may be categorized as serious in 1 and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Safety data set included all participants who received at least one dose of the study drug.	0.95% 1/105 • From baseline up to 12 weeks Same event may appear as AE and serious AE, what is presented are distinct events. Event may be categorized as serious in 1 and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Safety data set included all participants who received at least one dose of the study drug.
Infections and infestations Pneumocystis jirovecii pneumonia	1.9% 2/104 • From baseline up to 12 weeks Same event may appear as AE and serious AE, what is presented are distinct events. Event may be categorized as serious in 1 and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Safety data set included all participants who received at least one dose of the study drug.	0.95% 1/105 • From baseline up to 12 weeks Same event may appear as AE and serious AE, what is presented are distinct events. Event may be categorized as serious in 1 and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Safety data set included all participants who received at least one dose of the study drug.
Infections and infestations Pneumonia	0.96% 1/104 • From baseline up to 12 weeks Same event may appear as AE and serious AE, what is presented are distinct events. Event may be categorized as serious in 1 and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Safety data set included all participants who received at least one dose of the study drug.	0.95% 1/105 • From baseline up to 12 weeks Same event may appear as AE and serious AE, what is presented are distinct events. Event may be categorized as serious in 1 and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Safety data set included all participants who received at least one dose of the study drug.
Infections and infestations Pneumonia bacterial	0.00% 0/104 • From baseline up to 12 weeks Same event may appear as AE and serious AE, what is presented are distinct events. Event may be categorized as serious in 1 and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Safety data set included all participants who received at least one dose of the study drug.	0.95% 1/105 • From baseline up to 12 weeks Same event may appear as AE and serious AE, what is presented are distinct events. Event may be categorized as serious in 1 and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Safety data set included all participants who received at least one dose of the study drug.
Injury, poisoning and procedural complications Femoral neck fracture	0.96% 1/104 • From baseline up to 12 weeks Same event may appear as AE and serious AE, what is presented are distinct events. Event may be categorized as serious in 1 and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Safety data set included all participants who received at least one dose of the study drug.	0.00% 0/105 • From baseline up to 12 weeks Same event may appear as AE and serious AE, what is presented are distinct events. Event may be categorized as serious in 1 and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Safety data set included all participants who received at least one dose of the study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Rectal cancer	0.96% 1/104 • From baseline up to 12 weeks Same event may appear as AE and serious AE, what is presented are distinct events. Event may be categorized as serious in 1 and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Safety data set included all participants who received at least one dose of the study drug.	0.00% 0/105 • From baseline up to 12 weeks Same event may appear as AE and serious AE, what is presented are distinct events. Event may be categorized as serious in 1 and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Safety data set included all participants who received at least one dose of the study drug.
Respiratory, thoracic and mediastinal disorders Interstitial lung disease	0.00% 0/104 • From baseline up to 12 weeks Same event may appear as AE and serious AE, what is presented are distinct events. Event may be categorized as serious in 1 and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Safety data set included all participants who received at least one dose of the study drug.	0.95% 1/105 • From baseline up to 12 weeks Same event may appear as AE and serious AE, what is presented are distinct events. Event may be categorized as serious in 1 and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Safety data set included all participants who received at least one dose of the study drug.

Other adverse events

Other adverse events
Measure	Tofacitinib Modified Release (MR) n=104 participants at risk Participants orally received 11 mg of tofacitinib MR tablets once daily and matching placebo of tofacitinib IR tablets twice daily for 12 weeks.	Tofacitinib Immediate Release (IR) n=105 participants at risk Participants orally received 5 mg of tofacitinib IR tablets twice daily and matching placebo of tofacitinib MR tablets once daily for 12 weeks.
Infections and infestations Nasopharyngitis	9.6% 10/104 • From baseline up to 12 weeks Same event may appear as AE and serious AE, what is presented are distinct events. Event may be categorized as serious in 1 and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Safety data set included all participants who received at least one dose of the study drug.	12.4% 13/105 • From baseline up to 12 weeks Same event may appear as AE and serious AE, what is presented are distinct events. Event may be categorized as serious in 1 and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Safety data set included all participants who received at least one dose of the study drug.

Additional Information

Pfizer ClinicalTrials.gov Call Center

Pfizer, Inc.

Phone: 1-800-718-1021

Email: [email protected]

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