Rheumatoid Arthritis
Conditions
Keywords
Rheumatoid Arthritis, Tofacitinib, CP-690,550, Xeljanz, methotrexate withdrawal, withdrawal study
Brief summary
This study is designed to evaluate the efficacy and safety of tofacitinib modified release formulation (11mg QD) versus tofacitinib modified release formulation plus continued methotrexate treatment in subjects with moderate to severe rheumatoid arthritis who are insufficiently responding to their stable dose of methotrexate treatment.
Interventions
DRUGMethotrexate
During the open-label run-in phase (Day 1 to Week 24), all subjects will receive one tablet open-label tofacitinib MR 11mg orally QD and open-label methotrexate capsule(s) orally every week at prior stabilized dose. During the double-blind phase, subjects who are randomized to the treatment arm will receive the same dosage of tofacitinib and methotrexate as describe above.
DRUGPlacebo
During the double-blind phase, subjects who are randomized to the comparison arm will receive 11mg QD tofacitinib and the placebo capsules matching for methotrexate.
DRUGCP-690,550
During the open-label run-in phase (Day 1 to Week 24), all subjects will receive one tablet open-label tofacitinib MR 11mg orally QD and open-label methotrexate capsule(s) orally every week at prior stabilized dose. During the double-blind phase, subjects who are randomized to the treatment arm will receive the same dosage of tofacitinib and methotrexate as describe above.
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria \- Must be 18 years of age or older. Have a score of 6 or greater on the 2010 American College of Rheumatology/European League Against Rheumatism Classification Criteria for Rheumatoid Arthritis at and/or prior to Screening Visit. * Have ≥4 tender/painful joints on motion and ≥4 swollen joints (28 joint counts) at both Screening Visit and Baseline Visit (Visit 1). * Have moderate to severe disease activity as defined by CDAI\>10 and DAS28-4(ESR) ≥3.2 at Baseline Visit. * Have taken an oral MTX treatment regimen (15-25mg/week) continuously for at least 4 months prior to the screening visit and has taken a stable weekly dose of oral MTX with supplemental folic acid or folinic acid for at least 4 weeks prior to the baseline visit (conversion from parenteral MTX to oral MTX will require stabilization of the treatment regimen for at least 1 month). * Subjects must screen negative for active tuberculosis or inadequately treated tuberculosis infection (active or latent). Key
Exclusion criteria
* Pregnant female subjects; breastfeeding female subjects; male subjects with partners currently pregnant; male subjects able to father children and female subjects of childbearing potential who are unwilling or unable to use 2 highly effective methods of contraception as outlined in this protocol for the duration of the study and for at least 3 months after the last dose of investigational product. * Subjects with infection or infection history; subjects with any current malignancy or a history of malignancy (except adequately treated or excised non-metastatic basal cell or squamous cell cancer of the skin or cervical carcinoma in situ); subjects with history of, or current evidence for, severe gastrointestinal narrowing (pathologic or iatrogenic); and subjects with history of documented diverticulitis. * Subjects with a history of insufficient response to ≥2 biologics, regardless of the class.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | Randomization (last non-missing measurement on or prior to the first dosing date in DB phase at Week 24), Week 48 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Double Blind Phase: Change From Randomization in DAS28-4 ESR at Week 36 | Randomization (last non-missing measurement on or prior to the first dosing date in DB phase at Week 24), Week 36 | 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. |
| Double Blind Phase: Change From Randomization in DAS28-4 (C-reactive Protein [CRP]) at Weeks 36 and 48 | Randomization (last non-missing measurement on or prior to the first dosing date in DB phase at Week 24), Weeks 36 and 48 | 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. |
| Double Blind Phase: Change From Randomization in Clinical Disease Activity Index (CDAI) at Weeks 36 and 48 | Randomization (last non-missing measurement on or prior to the first dosing date in DB phase at Week 24), Weeks 36 and 48 | 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). |
| 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 | Weeks 36 and 48 | 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. |
| Double Blind Phase: Change From Randomization in Simplified Disease Activity Index (SDAI) at Weeks 36 and 48 | Randomization (last non-missing measurement on or prior to the first dosing date in DB phase at Week 24), Weeks 36 and 48 | 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). |
| 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 | Weeks 36 and 48 | 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. |
| Double Blind Phase: Percentage of Participants With LDA Assessed by DAS28-4 (CRP) <=3.2 at Weeks 36 and 48 | Weeks 36 and 48 | 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. |
| Double Blind Phase: Percentage of Participants With LDA Assessed by CDAI <=10 at Weeks 36 and 48 | Weeks 36 and 48 | 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). |
| Double Blind Phase: Percentage of Participants With LDA Assessed by SDAI <=11 at Weeks 36 and 48 | Weeks 36 and 48 | 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). |
| Double Blind Phase: Percentage of Participants With Remission Assessed by DAS28-4 (ESR) Less Than [<] 2.6 at Weeks 36 and 48 | Weeks 36 and 48 | 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. |
| Double Blind Phase: Percentage of Participants With Remission Assessed by DAS28-4 (CRP) <2.6 at Weeks 36 and 48 | Weeks 36 and 48 | 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. |
| Double Blind Phase: Percentage of Participants With Remission Assessed by CDAI <=2.8 at Weeks 36 and 48 | Weeks 36 and 48 | 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). |
| Double Blind Phase: Change From Randomization in the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scale Scores at Weeks 36 and 48 | Randomization (last non-missing measurement on or prior to the first dosing date in DB phase at Week 24), Weeks 36 and 48 | 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. |
| Double Blind Phase: Percentage of Participants Achieving an Improvement of at Least 0.22 Units in HAQ-DI at Weeks 36 and 48 | Baseline (Day 1), Weeks 36 and 48 | 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. |
| Double Blind Phase: Percentage of Participants With Remission Assessed by SDAI <=3.3 at Weeks 36 and 48 | Weeks 36 and 48 | 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). |
| Double Blind Phase: Percentage of Participants Achieving an American College of Rheumatology 20 Percent (%) (ACR20) Response at Weeks 36 and 48 | Baseline (Day 1), Weeks 36 and 48 | 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). |
| Double Blind Phase: Percentage of Participants Achieving an American College of Rheumatology 50% (ACR50) Response at Weeks 36 and 48 | Baseline (Day 1), Weeks 36 and 48 | 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). |
| Double Blind Phase: Percentage of Participants Achieving an American College of Rheumatology 70% (ACR70) Response at Weeks 36 and 48 | Baseline (Day 1), Weeks 36 and 48 | 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). |
| Double Blind Phase: Change From Randomization in Health Assessment Questionnaire-Disability Index (HAQ-DI) at Weeks 36 and 48 | Randomization (last non-missing measurement on or prior to the first dosing date in DB phase at Week 24), Weeks 36 and 48 | 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. |
| Double Blind Phase: Change From Randomization in the Short Form 36 (SF-36) Health Survey 8 Domain Scores at Weeks 36 and 48 | Randomization (last non-missing measurement on or prior to the first dosing date in DB phase at Week 24), Weeks 36 and 48 | 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. |
| Double Blind Phase: Change From Randomization in the SF-36 Health Survey Component Scores at Weeks 36 and 48 | Randomization (last non-missing measurement on or prior to the first dosing date in DB phase at Week 24), Weeks 36 and 48 | 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. |
| Double Blind Phase: Change From Randomization in the Work Productivity and Activity Impairment (WPAI) Scores at Week 36 and 48 | Randomization (last non-missing measurement on or prior to the first dosing date in DB phase at Week 24), Week 36 and 48 | 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. |
| Double Blind Phase: Change From Randomization in the European Quality of Life - 5 Dimensions Questionnaire (EQ-5D) Scores at Weeks 36 and 48 | Randomization (last non-missing measurement on or prior to the first dosing date in DB phase at Week 24), Weeks 36 and 48 | 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious AEs | For OL Phase: Baseline up to Week 24; For DB Phase: Week 24 up to Week 52 (up to 28 days after last dose) | 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. |
| Number of Participants With Abnormal Laboratory Parameters | For OL Phase: Baseline up to Week 24; For DB Phase: Week 24 up to Week 48 | 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. |
Countries
Australia, Belgium, Bulgaria, Czechia, Germany, Hungary, Mexico, Philippines, Poland, Russia, Slovakia, South Africa, South Korea, Spain, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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). | 694 |
| Total | 694 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Double Blind Phase (24 Weeks) | Adverse Event | 0 | 6 | 6 |
| Double Blind Phase (24 Weeks) | Death | 0 | 0 | 2 |
| Double Blind Phase (24 Weeks) | Insufficient Clinical Response | 0 | 6 | 1 |
| Double Blind Phase (24 Weeks) | Lost to Follow-up | 0 | 1 | 1 |
| Double Blind Phase (24 Weeks) | Other | 0 | 2 | 5 |
| Double Blind Phase (24 Weeks) | Protocol Violation | 0 | 5 | 2 |
| Double Blind Phase (24 Weeks) | Randomized but not Treated | 0 | 3 | 0 |
| Double Blind Phase (24 Weeks) | Screen Failure | 0 | 1 | 0 |
| Double Blind Phase (24 Weeks) | Withdrawal by Subject | 0 | 5 | 2 |
| Open Label Phase (24 Weeks) | Adverse Event | 39 | 0 | 0 |
| Open Label Phase (24 Weeks) | Insufficient Clinical Response | 7 | 0 | 0 |
| Open Label Phase (24 Weeks) | Lost to Follow-up | 8 | 0 | 0 |
| Open Label Phase (24 Weeks) | Medication error,no linked adverse event | 2 | 0 | 0 |
| Open Label Phase (24 Weeks) | Other | 4 | 0 | 0 |
| Open Label Phase (24 Weeks) | Protocol Violation | 5 | 0 | 0 |
| Open Label Phase (24 Weeks) | Withdrawal by Subject | 6 | 0 | 0 |
Baseline characteristics
| Characteristic | Open Label: Tofacitinib 11 mg + Methotrexate |
|---|---|
| Age, Continuous | 56.77 Years STANDARD_DEVIATION 11.83 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 59 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 635 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race/Ethnicity, Customized Asian | 37 Participants |
| Race/Ethnicity, Customized Black or African American | 33 Participants |
| Race/Ethnicity, Customized Others | 30 Participants |
| Race/Ethnicity, Customized White | 594 Participants |
| Sex: Female, Male Female | 532 Participants |
| Sex: Female, Male Male | 162 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 694 | 0 / 264 | 2 / 266 |
| other Total, other adverse events | 158 / 694 | 24 / 264 | 31 / 266 |
| serious Total, serious adverse events | 20 / 694 | 10 / 264 | 5 / 266 |
Outcome results
Primary
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
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.
Time frame: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Double Blind: Tofacitinib 11 mg + Methotrexate Placebo | 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 |
| Double Blind: Tofacitinib 11mg + Methotrexate | 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 | 0.03 units on a scale | Standard Error 0.07 |
Comparison: Linear mixed-effect model of repeated measures (MMRM) was used that included the fixed effects of treatment, visit, treatment-by-visit interaction, prior use of a biological disease-modifying anti-rheumatic drug (bDMARD), and baseline DAS28-4 (ESR) value as a covariate.p-value: 0.000595% CI: [0.12, 0.48]MMRM
Secondary
Double Blind Phase: Change From Randomization in Clinical Disease Activity Index (CDAI) at Weeks 36 and 48
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).
Time frame: 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.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Double Blind: Tofacitinib 11 mg + Methotrexate Placebo | 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 |
| Double Blind: Tofacitinib 11 mg + Methotrexate Placebo | 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 |
| Double Blind: Tofacitinib 11mg + Methotrexate | Double Blind Phase: Change From Randomization in Clinical Disease Activity Index (CDAI) at Weeks 36 and 48 | Change at Week 36 | 1.84 units on a scale | Standard Error 0.48 |
| Double Blind: Tofacitinib 11mg + Methotrexate | Double Blind Phase: Change From Randomization in Clinical Disease Activity Index (CDAI) at Weeks 36 and 48 | Change at Week 48 | 0.84 units on a scale | Standard Error 0.47 |
Comparison: Change at Week 36: Linear MMRM was used that included the fixed effects of treatment, visit, treatment-by-visit interaction, prior use of a bDMARD and baseline CDAI value as a covariate.95% CI: [0.4, 3.07]
Comparison: Change at Week 48: Linear MMRM was used that included the fixed effects of treatment, visit, treatment-by-visit interaction, prior use of a bDMARD and baseline CDAI value as a covariate.95% CI: [0.83, 3.43]
Secondary
Double Blind Phase: Change From Randomization in DAS28-4 (C-reactive Protein [CRP]) at Weeks 36 and 48
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.
Time frame: 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.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Double Blind: Tofacitinib 11 mg + Methotrexate Placebo | 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 |
| Double Blind: Tofacitinib 11 mg + Methotrexate Placebo | 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 |
| Double Blind: Tofacitinib 11mg + Methotrexate | Double Blind Phase: Change From Randomization in DAS28-4 (C-reactive Protein [CRP]) at Weeks 36 and 48 | Change at Week 36 | 0.13 units on a scale | Standard Error 0.06 |
| Double Blind: Tofacitinib 11mg + Methotrexate | Double Blind Phase: Change From Randomization in DAS28-4 (C-reactive Protein [CRP]) at Weeks 36 and 48 | Change at Week 48 | 0.01 units on a scale | Standard Error 0.06 |
Comparison: Change at Week 36: Linear MMRM was used that included the fixed effects of treatment, visit, treatment -by-visit interaction, prior use of a bDMARD and baseline DAS28-4 (CRP) value as a covariate.95% CI: [0.08, 0.43]
Comparison: Change at Week 48: Linear MMRM was used that included the fixed effects of treatment, visit, treatment -by-visit interaction, prior use of a bDMARD and baseline DAS28-4 (CRP) value as a covariate.95% CI: [0.11, 0.45]
Secondary
Double Blind Phase: Change From Randomization in DAS28-4 ESR at Week 36
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.
Time frame: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Double Blind: Tofacitinib 11 mg + Methotrexate Placebo | Double Blind Phase: Change From Randomization in DAS28-4 ESR at Week 36 | 0.40 units on a scale | Standard Error 0.07 |
| Double Blind: Tofacitinib 11mg + Methotrexate | Double Blind Phase: Change From Randomization in DAS28-4 ESR at Week 36 | 0.18 units on a scale | Standard Error 0.07 |
Comparison: Linear MMRM was used that included the fixed effects of treatment, visit, treatment-by-visit interaction, prior use of a bDMARD and baseline DAS28-4 (ESR) value as a covariate.95% CI: [0.03, 0.41]
Secondary
Double Blind Phase: Change From Randomization in Health Assessment Questionnaire-Disability Index (HAQ-DI) at Weeks 36 and 48
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.
Time frame: 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.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Double Blind: Tofacitinib 11 mg + Methotrexate Placebo | 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 |
| Double Blind: Tofacitinib 11 mg + Methotrexate Placebo | 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 |
| Double Blind: Tofacitinib 11mg + Methotrexate | Double Blind Phase: Change From Randomization in Health Assessment Questionnaire-Disability Index (HAQ-DI) at Weeks 36 and 48 | Change at Week 36 | 0.01 units on a scale | Standard Error 0.03 |
| Double Blind: Tofacitinib 11mg + Methotrexate | Double Blind Phase: Change From Randomization in Health Assessment Questionnaire-Disability Index (HAQ-DI) at Weeks 36 and 48 | Change at Week 48 | 0.00 units on a scale | Standard Error 0.03 |
Comparison: Change at Week 36: Linear MMRM was used that included the fixed effects of treatment, visit, treatment-by-visit interaction, prior use of a bDMARD and baseline HAQ-DI.95% CI: [0.02, 0.16]
Comparison: Change at Week 48: Linear MMRM was used that included the fixed effects of treatment, visit, treatment-by-visit interaction, prior use of a bDMARD and baseline HAQ-DI.95% CI: [-0.06, 0.09]
Secondary
Double Blind Phase: Change From Randomization in Simplified Disease Activity Index (SDAI) at Weeks 36 and 48
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).
Time frame: 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.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Double Blind: Tofacitinib 11 mg + Methotrexate Placebo | 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 |
| Double Blind: Tofacitinib 11 mg + Methotrexate Placebo | 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 0.5 |
| Double Blind: Tofacitinib 11mg + Methotrexate | Double Blind Phase: Change From Randomization in Simplified Disease Activity Index (SDAI) at Weeks 36 and 48 | Change at Week 48 | 0.94 units on a scale | Standard Error 0.49 |
| Double Blind: Tofacitinib 11mg + Methotrexate | Double Blind Phase: Change From Randomization in Simplified Disease Activity Index (SDAI) at Weeks 36 and 48 | Change at Week 36 | 1.88 units on a scale | Standard Error 0.51 |
Comparison: Change at Week 36: Linear MMRM was used that included the fixed effects of treatment, visit, treatment-by-visit interaction, prior use of a bDMARD and baseline SDAI value as a covariate.95% CI: [0.53, 3.37]
Comparison: Change at Week 48: Linear MMRM was used that included the fixed effects of treatment, visit, treatment-by-visit interaction, prior use of a bDMARD and baseline SDAI value as a covariate.95% CI: [0.86, 3.59]
Secondary
Double Blind Phase: Change From Randomization in the European Quality of Life - 5 Dimensions Questionnaire (EQ-5D) Scores at Weeks 36 and 48
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.
Time frame: 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.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Double Blind: Tofacitinib 11 mg + Methotrexate Placebo | 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 |
| Double Blind: Tofacitinib 11 mg + Methotrexate Placebo | 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 |
| Double Blind: Tofacitinib 11mg + Methotrexate | 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 | -0.01 units on a scale | Standard Error 0.01 |
| Double Blind: Tofacitinib 11mg + Methotrexate | 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 | 0.00 units on a scale | Standard Error 0.01 |
Comparison: Change at Week 36: Linear MMRM was used that included the fixed effects of treatment, visit, treatment-by-visit interaction, prior use of a bDMARD, and baseline EQ-5D score as a covariate.95% CI: [-0.07, -0.01]
Comparison: Change at Week 48: Linear MMRM was used that included the fixed effects of treatment, visit, treatment-by-visit interaction, prior use of a bDMARD, and baseline EQ-5D score as a covariate.95% CI: [-0.06, 0.01]
Secondary
Double Blind Phase: Change From Randomization in the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scale Scores at Weeks 36 and 48
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.
Time frame: 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.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Double Blind: Tofacitinib 11 mg + Methotrexate Placebo | 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 |
| Double Blind: Tofacitinib 11 mg + Methotrexate Placebo | 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 |
| Double Blind: Tofacitinib 11mg + Methotrexate | 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 | -0.80 units on a scale | Standard Error 0.43 |
| Double Blind: Tofacitinib 11mg + Methotrexate | 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 | -0.52 units on a scale | Standard Error 0.45 |
Comparison: Change at Week 36: Linear MMRM was used that included the fixed effects of treatment, visit, treatment-by-visit interaction, prior use of a bDMARD, and baseline FACIT - fatigue scale score as a covariate.95% CI: [-1.37, 1]
Comparison: Change at Week 48: Linear MMRM was used that included the fixed effects of treatment, visit, treatment-by-visit interaction, prior use of a bDMARD, and baseline FACIT - fatigue scale score as a covariate.95% CI: [-1.07, 1.44]
Secondary
Double Blind Phase: Change From Randomization in the SF-36 Health Survey Component Scores at Weeks 36 and 48
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.
Time frame: 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.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Double Blind: Tofacitinib 11 mg + Methotrexate Placebo | 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 |
| Double Blind: Tofacitinib 11 mg + Methotrexate Placebo | 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 |
| Double Blind: Tofacitinib 11 mg + Methotrexate Placebo | 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 |
| Double Blind: Tofacitinib 11 mg + Methotrexate Placebo | 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 |
| Double Blind: Tofacitinib 11mg + Methotrexate | 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 | 0.03 units on a scale | Standard Error 0.5 |
| Double Blind: Tofacitinib 11mg + Methotrexate | 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 | -0.60 units on a scale | Standard Error 0.43 |
| Double Blind: Tofacitinib 11mg + Methotrexate | 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 | -0.92 units on a scale | Standard Error 0.43 |
| Double Blind: Tofacitinib 11mg + Methotrexate | 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 | -0.43 units on a scale | Standard Error 0.47 |
Comparison: Change at Week 36: Physical Component Score- Linear MMRM was used that included the fixed effects of treatment, visit, treatment-by-visit interaction, prior use of a bDMARD, and baseline SF-36 physical component score- as a covariate.95% CI: [-2.01, 0.37]
Comparison: Change at Week 48: Physical Component Score- Linear MMRM was used that included the fixed effects of treatment, visit, treatment-by-visit interaction, prior use of a biological disease-modifying anti-rheumatic drug (DMARD), and baseline SF-36 physical component score- as a covariate.95% CI: [-1.11, 1.29]
Comparison: Change at Week 36: Mental Component Score- Linear MMRM was used that included the fixed effects of treatment, visit, treatment-by-visit interaction, prior use of a bDMARD, and baseline SF-36 mental component score as a covariate.95% CI: [-2.13, 0.49]
Comparison: Change at Week 48: Mental Component Score- Linear MMRM was used that included the fixed effects of treatment, visit, treatment-by-visit interaction, prior use of a bDMARD, and baseline SF-36 mental component score as a covariate.95% CI: [-2.06, 0.7]
Secondary
Double Blind Phase: Change From Randomization in the Short Form 36 (SF-36) Health Survey 8 Domain Scores at Weeks 36 and 48
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.
Time frame: 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.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Double Blind: Tofacitinib 11 mg + Methotrexate Placebo | 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 |
| Double Blind: Tofacitinib 11 mg + Methotrexate Placebo | 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 |
| Double Blind: Tofacitinib 11 mg + Methotrexate Placebo | 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 |
| Double Blind: Tofacitinib 11 mg + Methotrexate Placebo | 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 |
| Double Blind: Tofacitinib 11 mg + Methotrexate Placebo | 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 0.5 |
| Double Blind: Tofacitinib 11 mg + Methotrexate Placebo | 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 |
| Double Blind: Tofacitinib 11 mg + Methotrexate Placebo | 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 |
| Double Blind: Tofacitinib 11 mg + Methotrexate Placebo | 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 |
| Double Blind: Tofacitinib 11 mg + Methotrexate Placebo | 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 |
| Double Blind: Tofacitinib 11 mg + Methotrexate Placebo | 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 0.5 |
| Double Blind: Tofacitinib 11 mg + Methotrexate Placebo | 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 |
| Double Blind: Tofacitinib 11 mg + Methotrexate Placebo | 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 |
| Double Blind: Tofacitinib 11 mg + Methotrexate Placebo | 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 |
| Double Blind: Tofacitinib 11 mg + Methotrexate Placebo | 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 0.5 |
| Double Blind: Tofacitinib 11 mg + Methotrexate Placebo | 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 |
| Double Blind: Tofacitinib 11 mg + Methotrexate Placebo | 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 |
| Double Blind: Tofacitinib 11mg + Methotrexate | 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 | -0.71 units on a scale | Standard Error 0.54 |
| Double Blind: Tofacitinib 11mg + Methotrexate | 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 | -0.32 units on a scale | Standard Error 0.5 |
| Double Blind: Tofacitinib 11mg + Methotrexate | 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 | -0.69 units on a scale | Standard Error 0.55 |
| Double Blind: Tofacitinib 11mg + Methotrexate | 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 | -0.15 units on a scale | Standard Error 0.5 |
| Double Blind: Tofacitinib 11mg + Methotrexate | 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 | -0.87 units on a scale | Standard Error 0.43 |
| Double Blind: Tofacitinib 11mg + Methotrexate | 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 | -0.97 units on a scale | Standard Error 0.48 |
| Double Blind: Tofacitinib 11mg + Methotrexate | 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 | -0.15 units on a scale | Standard Error 0.5 |
| Double Blind: Tofacitinib 11mg + Methotrexate | 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 | -0.55 units on a scale | Standard Error 0.52 |
| Double Blind: Tofacitinib 11mg + Methotrexate | 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 | -0.58 units on a scale | Standard Error 0.52 |
| Double Blind: Tofacitinib 11mg + Methotrexate | 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 | 0.12 units on a scale | Standard Error 0.54 |
| Double Blind: Tofacitinib 11mg + Methotrexate | 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 | -0.36 units on a scale | Standard Error 0.54 |
| Double Blind: Tofacitinib 11mg + Methotrexate | 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 | -0.25 units on a scale | Standard Error 0.52 |
| Double Blind: Tofacitinib 11mg + Methotrexate | 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 | -1.05 units on a scale | Standard Error 0.44 |
| Double Blind: Tofacitinib 11mg + Methotrexate | 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 | -0.88 units on a scale | Standard Error 0.49 |
| Double Blind: Tofacitinib 11mg + Methotrexate | 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 | -0.02 units on a scale | Standard Error 0.47 |
| Double Blind: Tofacitinib 11mg + Methotrexate | 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 | -0.84 units on a scale | Standard Error 0.49 |
Comparison: Change at Week 36: Physical Functioning- Linear MMRM was used that included the fixed effects of treatment, visit, treatment-by-visit interaction, prior use of a bDMARD, and baseline SF-36 physical component score as a covariate.95% CI: [-1.79, 0.92]
Comparison: Change at Week 48: Physical Functioning- Linear MMRM was used that included the fixed effects of treatment, visit, treatment-by-visit interaction, prior use of a bDMARD, and baseline SF-36 physical component score as a covariate.95% CI: [-0.82, 1.85]
Comparison: Change at Week 36: Role Physical Score- Linear MMRM was used that included the fixed effects of treatment, visit, treatment-by-visit interaction, prior use of a bDMARD, and baseline SF-36 role physical score score as a covariate.95% CI: [-2.97, -0.37]
Comparison: Change at Week 48: Role Physical Score- Linear MMRM was used that included the fixed effects of treatment, visit, treatment-by-visit interaction, prior use of a bDMARD, and baseline SF-36 role physical score score as a covariate.95% CI: [-2.13, 0.66]
Comparison: Change at Week 36: Social functioning- Linear MMRM was used that included the fixed effects of treatment, visit, treatment-by-visit interaction, prior use of a bDMARD, and baseline SF-36 Social functioning score as a covariate.95% CI: [-1.5, 1.21]
Comparison: Change at Week 48: Social functioning- Linear MMRM was used that included the fixed effects of treatment, visit, treatment-by-visit interaction, prior use of a bDMARD, and baseline SF-36 Social functioning score as a covariate.95% CI: [-1.95, 0.93]
Comparison: Change at Week 36: Bodily Pain Score- Linear MMRM was used that included the fixed effects of treatment, visit, treatment-by-visit interaction, prior use of a bDMARD, and baseline SF-36 bodily pain score as a covariate.95% CI: [-2.9, -0.01]
Comparison: Change at Week 48: Bodily Pain Score- Linear MMRM was used that included the fixed effects of treatment, visit, treatment-by-visit interaction, prior use of a bDMARD, and baseline SF-36 bodily pain score as a covariate.95% CI: [-2.23, 0.73]
Comparison: Change at Week 36: Mental Health Score- Linear MMRM was used that included the fixed effects of treatment, visit, treatment-by-visit interaction, prior use of a bDMARD, and baseline SF-36 mental health score as a covariate.95% CI: [-2.29, 0.49]
Comparison: Change at Week 48: Mental Health Score- Linear MMRM was used that included the fixed effects of treatment, visit, treatment-by-visit interaction, prior use of a bDMARD, and baseline SF-36 mental health score as a covariate.95% CI: [-1.94, 1.02]
Comparison: Change at Week 36: Role Emotional Score- Linear MMRM was used that included the fixed effects of treatment, visit, treatment-by-visit interaction, prior use of a bDMARD, and baseline SF-36 role emotional score as a covariate.95% CI: [-2.64, 0.43]
Comparison: Change at Week 48: Role Emotional Score- Linear MMRM was used that included the fixed effects of treatment, visit, treatment-by-visit interaction, prior use of a bDMARD, and baseline SF-36 role emotional score as a covariate.95% CI: [-1.95, 1.01]
Comparison: Change at Week 36: Vitality Score- Linear MMRM was used that included the fixed effects of treatment, visit, treatment-by-visit interaction, prior use of a bDMARD, and baseline SF-36 vitality score as a covariate.95% CI: [-2.52, 0.22]
Comparison: Change at Week 48: Vitality Score- Linear MMRM was used that included the fixed effects of treatment, visit, treatment-by-visit interaction, prior use of a bDMARD, and baseline SF-36 vitality score as a covariate.95% CI: [-1.94, 0.91]
Comparison: Change at Week 36: General Health Perception Score- Linear MMRM was used that included the fixed effects of treatment, visit, treatment-by-visit interaction, prior use of a bDMARD, and baseline SF-36 general health perception score as a covariate.95% CI: [-1.3, 1.08]
Comparison: Change at Week 48: General Health Perception Score- Linear MMRM was used that included the fixed effects of treatment, visit, treatment-by-visit interaction, prior use of a bDMARD, and baseline SF-36 general health perception score as a covariate.95% CI: [-0.6, 1.83]
Secondary
Double Blind Phase: Change From Randomization in the Work Productivity and Activity Impairment (WPAI) Scores at Week 36 and 48
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.
Time frame: 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.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Double Blind: Tofacitinib 11 mg + Methotrexate Placebo | 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 |
| Double Blind: Tofacitinib 11 mg + Methotrexate Placebo | 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 1.7 |
| Double Blind: Tofacitinib 11 mg + Methotrexate Placebo | 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 2.2 |
| Double Blind: Tofacitinib 11 mg + Methotrexate Placebo | 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 |
| Double Blind: Tofacitinib 11 mg + Methotrexate Placebo | 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 |
| Double Blind: Tofacitinib 11 mg + Methotrexate Placebo | 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 |
| Double Blind: Tofacitinib 11 mg + Methotrexate Placebo | 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 |
| Double Blind: Tofacitinib 11 mg + Methotrexate Placebo | 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 |
| Double Blind: Tofacitinib 11mg + Methotrexate | 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 | 0.19 percentage impairment | Standard Error 2.41 |
| Double Blind: Tofacitinib 11mg + Methotrexate | 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 | -3.00 percentage impairment | Standard Error 1.69 |
| Double Blind: Tofacitinib 11mg + Methotrexate | 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 | 0.81 percentage impairment | Standard Error 1.34 |
| Double Blind: Tofacitinib 11mg + Methotrexate | 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 | 0.67 percentage impairment | Standard Error 2.07 |
| Double Blind: Tofacitinib 11mg + Methotrexate | 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 | 5.45 percentage impairment | Standard Error 2.91 |
| Double Blind: Tofacitinib 11mg + Methotrexate | 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 | -1.69 percentage impairment | Standard Error 1.61 |
| Double Blind: Tofacitinib 11mg + Methotrexate | 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 | 1.25 percentage impairment | Standard Error 1.46 |
| Double Blind: Tofacitinib 11mg + Methotrexate | 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 | 3.72 percentage impairment | Standard Error 2.61 |
Comparison: Change at Week 36: Absenteeism Score- Linear MMRM was used that included the fixed effects of treatment, visit, treatment-by-visit interaction, prior use of a bDMARD, and baseline WPAI absenteeism score as a covariate.95% CI: [-3.14, 6.37]
Comparison: Change at Week 48: Absenteeism Score- Linear MMRM was used that included the fixed effects of treatment, visit, treatment-by-visit interaction, prior use of a bDMARD, and baseline WPAI absenteeism score as a covariate.95% CI: [-5.01, 3.99]
Comparison: Change at Week 36: Daily activity impairment- Linear MMRM was used that included the fixed effects of treatment, visit, treatment-by-visit interaction, prior use of a bDMARD, and baseline WPAI daily activity impairment score as a covariate.95% CI: [-0.51, 6.89]
Comparison: Change at Week 48: Daily activity impairment- Linear MMRM was used that included the fixed effects of treatment, visit, treatment-by-visit interaction, prior use of a bDMARD, and baseline WPAI daily activity impairment score as a covariate.95% CI: [-2.41, 5.61]
Comparison: Change at Week 36: Presenteeism- Linear MMRM was used that included the fixed effects of treatment, visit, treatment-by-visit interaction, prior use of a bDMARD, and baseline WPAI presenteeism score as a covariate.95% CI: [-2.84, 8.87]
Comparison: Change at Week 48: Presenteeism- Linear MMRM was used that included the fixed effects of treatment, visit, treatment-by-visit interaction, prior use of a bDMARD, and baseline WPAI presenteeism score as a covariate.95% CI: [-8.34, 6.54]
Comparison: Change at Week 36: Work productivity loss- Linear MMRM was used that included the fixed effects of treatment, visit, treatment-by-visit interaction, prior use of a bDMARD, and baseline WPAI work productivity loss score as a covariate.95% CI: [-3.97, 9.65]
Comparison: Change at Week 48: Work productivity loss- Linear MMRM was used that included the fixed effects of treatment, visit, treatment-by-visit interaction, prior use of a bDMARD, and baseline WPAI work productivity loss score as a covariate.95% CI: [-10.72, 5.8]
Secondary
Double Blind Phase: Percentage of Participants Achieving an American College of Rheumatology 20 Percent (%) (ACR20) Response at Weeks 36 and 48
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).
Time frame: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Double Blind: Tofacitinib 11 mg + Methotrexate Placebo | 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 |
| Double Blind: Tofacitinib 11 mg + Methotrexate Placebo | 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 |
| Double Blind: Tofacitinib 11mg + Methotrexate | Double Blind Phase: Percentage of Participants Achieving an American College of Rheumatology 20 Percent (%) (ACR20) Response at Weeks 36 and 48 | Week 36 | 80.83 percentage of participants |
| Double Blind: Tofacitinib 11mg + Methotrexate | Double Blind Phase: Percentage of Participants Achieving an American College of Rheumatology 20 Percent (%) (ACR20) Response at Weeks 36 and 48 | Week 48 | 79.70 percentage of participants |
Comparison: Week 3695% CI: [-14.06, 0.14]
Comparison: Week 4895% CI: [-13.8, 0.61]
Secondary
Double Blind Phase: Percentage of Participants Achieving an American College of Rheumatology 50% (ACR50) Response at Weeks 36 and 48
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).
Time frame: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Double Blind: Tofacitinib 11 mg + Methotrexate Placebo | 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 |
| Double Blind: Tofacitinib 11 mg + Methotrexate Placebo | 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 |
| Double Blind: Tofacitinib 11mg + Methotrexate | Double Blind Phase: Percentage of Participants Achieving an American College of Rheumatology 50% (ACR50) Response at Weeks 36 and 48 | Week 48 | 67.29 percentage of participants |
| Double Blind: Tofacitinib 11mg + Methotrexate | Double Blind Phase: Percentage of Participants Achieving an American College of Rheumatology 50% (ACR50) Response at Weeks 36 and 48 | Week 36 | 66.54 percentage of participants |
Comparison: Week 3695% CI: [-21.01, -4.48]
Comparison: Week 4895% CI: [-20.22, -3.75]
Secondary
Double Blind Phase: Percentage of Participants Achieving an American College of Rheumatology 70% (ACR70) Response at Weeks 36 and 48
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).
Time frame: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Double Blind: Tofacitinib 11 mg + Methotrexate Placebo | 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 |
| Double Blind: Tofacitinib 11 mg + Methotrexate Placebo | 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 |
| Double Blind: Tofacitinib 11mg + Methotrexate | Double Blind Phase: Percentage of Participants Achieving an American College of Rheumatology 70% (ACR70) Response at Weeks 36 and 48 | Week 48 | 42.86 percentage of participants |
| Double Blind: Tofacitinib 11mg + Methotrexate | Double Blind Phase: Percentage of Participants Achieving an American College of Rheumatology 70% (ACR70) Response at Weeks 36 and 48 | Week 36 | 40.98 percentage of participants |
Comparison: Week 3695% CI: [-13.63, 2.89]
Comparison: Week 4895% CI: [-13.32, 3.36]
Secondary
Double Blind Phase: Percentage of Participants Achieving an Improvement of at Least 0.22 Units in HAQ-DI at Weeks 36 and 48
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.
Time frame: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Double Blind: Tofacitinib 11 mg + Methotrexate Placebo | 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 |
| Double Blind: Tofacitinib 11 mg + Methotrexate Placebo | 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 |
| Double Blind: Tofacitinib 11mg + Methotrexate | 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 | 75.19 percentage of participants |
| Double Blind: Tofacitinib 11mg + Methotrexate | 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 | 77.07 percentage of participants |
Comparison: Week 3695% CI: [-17.61, -2.42]
Comparison: Week 4895% CI: [-14.26, 1]
Secondary
Double Blind Phase: Percentage of Participants With LDA Assessed by CDAI <=10 at Weeks 36 and 48
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).
Time frame: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Double Blind: Tofacitinib 11 mg + Methotrexate Placebo | Double Blind Phase: Percentage of Participants With LDA Assessed by CDAI <=10 at Weeks 36 and 48 | Week 36 | 66.29 percentage of participants |
| Double Blind: Tofacitinib 11 mg + Methotrexate Placebo | Double Blind Phase: Percentage of Participants With LDA Assessed by CDAI <=10 at Weeks 36 and 48 | Week 48 | 65.15 percentage of participants |
| Double Blind: Tofacitinib 11mg + Methotrexate | Double Blind Phase: Percentage of Participants With LDA Assessed by CDAI <=10 at Weeks 36 and 48 | Week 36 | 73.68 percentage of participants |
| Double Blind: Tofacitinib 11mg + Methotrexate | Double Blind Phase: Percentage of Participants With LDA Assessed by CDAI <=10 at Weeks 36 and 48 | Week 48 | 77.07 percentage of participants |
Comparison: Week 3695% CI: [-15.17, 0.38]
Comparison: Week 4895% CI: [-19.56, -4.26]
Secondary
Double Blind Phase: Percentage of Participants With LDA Assessed by DAS28-4 (CRP) <=3.2 at Weeks 36 and 48
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.
Time frame: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Double Blind: Tofacitinib 11 mg + Methotrexate Placebo | 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 |
| Double Blind: Tofacitinib 11 mg + Methotrexate Placebo | 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 |
| Double Blind: Tofacitinib 11mg + Methotrexate | Double Blind Phase: Percentage of Participants With LDA Assessed by DAS28-4 (CRP) <=3.2 at Weeks 36 and 48 | Week 36 | 70.68 percentage of participants |
| Double Blind: Tofacitinib 11mg + Methotrexate | Double Blind Phase: Percentage of Participants With LDA Assessed by DAS28-4 (CRP) <=3.2 at Weeks 36 and 48 | Week 48 | 74.44 percentage of participants |
Comparison: Week 3695% CI: [-13.07, 2.77]
Comparison: Week 4895% CI: [-16.28, -0.76]
Secondary
Double Blind Phase: Percentage of Participants With LDA Assessed by SDAI <=11 at Weeks 36 and 48
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).
Time frame: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Double Blind: Tofacitinib 11 mg + Methotrexate Placebo | Double Blind Phase: Percentage of Participants With LDA Assessed by SDAI <=11 at Weeks 36 and 48 | Week 36 | 66.29 percentage of participants |
| Double Blind: Tofacitinib 11 mg + Methotrexate Placebo | Double Blind Phase: Percentage of Participants With LDA Assessed by SDAI <=11 at Weeks 36 and 48 | Week 48 | 66.29 percentage of participants |
| Double Blind: Tofacitinib 11mg + Methotrexate | Double Blind Phase: Percentage of Participants With LDA Assessed by SDAI <=11 at Weeks 36 and 48 | Week 36 | 73.31 percentage of participants |
| Double Blind: Tofacitinib 11mg + Methotrexate | Double Blind Phase: Percentage of Participants With LDA Assessed by SDAI <=11 at Weeks 36 and 48 | Week 48 | 76.32 percentage of participants |
Comparison: Week 3695% CI: [-14.81, 0.77]
Comparison: Week 4895% CI: [-17.68, -2.37]
Secondary
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
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.
Time frame: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Double Blind: Tofacitinib 11 mg + Methotrexate Placebo | 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 |
| Double Blind: Tofacitinib 11 mg + Methotrexate Placebo | 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 |
| Double Blind: Tofacitinib 11mg + Methotrexate | 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 | 48.12 percentage of participants |
| Double Blind: Tofacitinib 11mg + Methotrexate | 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 | 49.62 percentage of participants |
Comparison: Week 3695% CI: [-14.15, 2.76]
Comparison: Week 4895% CI: [-13.04, 3.94]
Secondary
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
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.
Time frame: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Double Blind: Tofacitinib 11 mg + Methotrexate Placebo | 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 |
| Double Blind: Tofacitinib 11 mg + Methotrexate Placebo | 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 |
| Double Blind: Tofacitinib 11mg + Methotrexate | 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 | 24.06 percentage of participants |
| Double Blind: Tofacitinib 11mg + Methotrexate | 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 | 23.68 percentage of participants |
Comparison: Week 3695% CI: [-15.27, -1.78]
Comparison: Week 4895% CI: [-8.5, 5.83]Two Sided
Secondary
Double Blind Phase: Percentage of Participants With Remission Assessed by CDAI <=2.8 at Weeks 36 and 48
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).
Time frame: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Double Blind: Tofacitinib 11 mg + Methotrexate Placebo | 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 |
| Double Blind: Tofacitinib 11 mg + Methotrexate Placebo | 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 |
| Double Blind: Tofacitinib 11mg + Methotrexate | Double Blind Phase: Percentage of Participants With Remission Assessed by CDAI <=2.8 at Weeks 36 and 48 | Week 36 | 32.33 percentage of participants |
| Double Blind: Tofacitinib 11mg + Methotrexate | Double Blind Phase: Percentage of Participants With Remission Assessed by CDAI <=2.8 at Weeks 36 and 48 | Week 48 | 30.83 percentage of participants |
Comparison: Week 3695% CI: [-16.44, -1.24]
Comparison: Week 4895% CI: [-10.18, 5.35]
Secondary
Double Blind Phase: Percentage of Participants With Remission Assessed by DAS28-4 (CRP) <2.6 at Weeks 36 and 48
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.
Time frame: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Double Blind: Tofacitinib 11 mg + Methotrexate Placebo | 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 |
| Double Blind: Tofacitinib 11 mg + Methotrexate Placebo | 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 |
| Double Blind: Tofacitinib 11mg + Methotrexate | Double Blind Phase: Percentage of Participants With Remission Assessed by DAS28-4 (CRP) <2.6 at Weeks 36 and 48 | Week 48 | 54.51 percentage of participants |
| Double Blind: Tofacitinib 11mg + Methotrexate | Double Blind Phase: Percentage of Participants With Remission Assessed by DAS28-4 (CRP) <2.6 at Weeks 36 and 48 | Week 36 | 55.64 percentage of participants |
Comparison: Week 3695% CI: [-14.12, 2.84]
Comparison: Week 4895% CI: [-12.62, 4.36]
Secondary
Double Blind Phase: Percentage of Participants With Remission Assessed by DAS28-4 (ESR) Less Than [<] 2.6 at Weeks 36 and 48
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.
Time frame: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Double Blind: Tofacitinib 11 mg + Methotrexate Placebo | 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 |
| Double Blind: Tofacitinib 11 mg + Methotrexate Placebo | 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 |
| Double Blind: Tofacitinib 11mg + Methotrexate | Double Blind Phase: Percentage of Participants With Remission Assessed by DAS28-4 (ESR) Less Than [<] 2.6 at Weeks 36 and 48 | Week 36 | 28.57 percentage of participants |
| Double Blind: Tofacitinib 11mg + Methotrexate | Double Blind Phase: Percentage of Participants With Remission Assessed by DAS28-4 (ESR) Less Than [<] 2.6 at Weeks 36 and 48 | Week 48 | 30.08 percentage of participants |
Comparison: Week 3695% CI: [-15.4, -0.82]
Comparison: Week 4895% CI: [-13.74, 1.32]
Secondary
Double Blind Phase: Percentage of Participants With Remission Assessed by SDAI <=3.3 at Weeks 36 and 48
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).
Time frame: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Double Blind: Tofacitinib 11 mg + Methotrexate Placebo | 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 |
| Double Blind: Tofacitinib 11 mg + Methotrexate Placebo | 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 |
| Double Blind: Tofacitinib 11mg + Methotrexate | Double Blind Phase: Percentage of Participants With Remission Assessed by SDAI <=3.3 at Weeks 36 and 48 | Week 36 | 31.58 percentage of participants |
| Double Blind: Tofacitinib 11mg + Methotrexate | Double Blind Phase: Percentage of Participants With Remission Assessed by SDAI <=3.3 at Weeks 36 and 48 | Week 48 | 31.95 percentage of participants |
Comparison: Week 3695% CI: [-16.38, -1.31]
Comparison: Week 4895% CI: [-10.99, 4.65]
Other Pre-specified
Number of Participants With Abnormal Laboratory Parameters
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.
Time frame: 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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Double Blind: Tofacitinib 11 mg + Methotrexate Placebo | Number of Participants With Abnormal Laboratory Parameters | 682 Participants |
| Double Blind: Tofacitinib 11mg + Methotrexate | Number of Participants With Abnormal Laboratory Parameters | 263 Participants |
| Double Blind: Tofacitinib 11mg + Methotrexate | Number of Participants With Abnormal Laboratory Parameters | 263 Participants |
Other Pre-specified
Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious AEs
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.
Time frame: 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.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Double Blind: Tofacitinib 11 mg + Methotrexate Placebo | Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious AEs | AEs | 362 Participants |
| Double Blind: Tofacitinib 11 mg + Methotrexate Placebo | Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious AEs | SAEs | 20 Participants |
| Double Blind: Tofacitinib 11mg + Methotrexate | Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious AEs | AEs | 107 Participants |
| Double Blind: Tofacitinib 11mg + Methotrexate | Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious AEs | SAEs | 10 Participants |
| Double Blind: Tofacitinib 11mg + Methotrexate | Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious AEs | AEs | 109 Participants |
| Double Blind: Tofacitinib 11mg + Methotrexate | Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious AEs | SAEs | 5 Participants |