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

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.