Methotrexate Withdrawal Study of Tofacitinib Modified Release Formulation in Subjects With Rheumatoid Arthritis
Sponsor
Pfizer (Industry)
Overall Status
Completed
CT.gov ID
NCT02831855
Collaborator
(none)
694
136
2
27.5
5.1
0.2
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 4 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
694 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A PHASE 3B/4 RANDOMIZED DOUBLE BLIND PLACEBO CONTROLLED STUDY OF METHOTREXATE (MTX) WITHDRAWAL IN SUBJECTS WITH RHEUMATOID ARTHRITIS (RA) TREATED WITH TOFACITINIB 11MG MODIFIED RELEASE (MR) FORMULATION
Actual Study Start Date
:
Sep 1, 2016
Actual Primary Completion Date
:
Nov 19, 2018
Actual Study Completion Date
:
Dec 17, 2018
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: CP-690,550 and methotrexate Open-label tofacitinib tablet and blinded methotrexate capsule |
Drug: CP-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.
Other Names:
Drug: Methotrexate
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.
|
| Placebo Comparator: CP-690,550 and placebo open-label tofacitinib tablet and blinded matching placebo for methotrexate capsule |
Drug: Placebo
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.
|
Outcome Measures
Primary Outcome Measures
- 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 Outcome Measures
- 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: 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 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: 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: 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.
- 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.
Other Outcome Measures
- 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.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Rheumatology Associates of North Alabama, PC | Huntsville | Alabama | United States | 35801-4418 |
| 2 | Arthrocare, Arthritiscare & Research, PC | Gilbert | Arizona | United States | 85234 |
| 3 | SunValley Arthritis Center, Ltd. | Peoria | Arizona | United States | 85381 |
| 4 | CHI St. Vincent Medical Group Hot Springs | Hot Springs | Arkansas | United States | 71913 |
| 5 | Med Investigations, Inc | Fair Oaks | California | United States | 95628 |
| 6 | HCP Clinical Research, LLC | Huntington Beach | California | United States | 92646 |
| 7 | Sierra Rheumatology | Roseville | California | United States | 95661 |
| 8 | Pacific Arthritis Center Medical Group | Santa Maria | California | United States | 93454 |
| 9 | Robin K. Dore, MD, Inc. | Tustin | California | United States | 92780 |
| 10 | Inland Rheumatology and Osteoporosis Medical Group | Upland | California | United States | 91786 |
| 11 | Inland Rheumatology Clinical Trials, Inc. | Upland | California | United States | 91786 |
| 12 | Desert Valley Medical Group | Victorville | California | United States | 92395 |
| 13 | AARDS Research Inc | Aventura | Florida | United States | 33180 |
| 14 | RASF-Clinical Research Inc | Boca Raton | Florida | United States | 33486 |
| 15 | Omega Research Consultants | DeBary | Florida | United States | 32713 |
| 16 | University of Florida College of Medicine - Jacksonville - Rheumatology Research | Jacksonville | Florida | United States | 32207 |
| 17 | University of Florida, Rheumatology at ACC | Jacksonville | Florida | United States | 32209 |
| 18 | Center for Arthritis and Rheumatic Diseases | Miami | Florida | United States | 33173 |
| 19 | Jeffrey Alper, MD | Naples | Florida | United States | 34102 |
| 20 | Medallion Clinical Research Institute, LLC | Naples | Florida | United States | 34102 |
| 21 | Suncoast Clinical Research, Inc. | New Port Richey | Florida | United States | 34652 |
| 22 | Florida Arthritis & Osteoporosis Center | Port Richey | Florida | United States | 34668 |
| 23 | Gulf Coast Medical Center | Port Richey | Florida | United States | 34668 |
| 24 | West Broward Rheumatology Associates, Inc. | Tamarac | Florida | United States | 33321 |
| 25 | USF Health Morsani Center for Advanced Healthcare | Tampa | Florida | United States | 33612 |
| 26 | BayCare Medical Group, Inc | Tampa | Florida | United States | 33614 |
| 27 | Institute of Arthritis Research | Idaho Falls | Idaho | United States | 83404 |
| 28 | Quincy Medical Group | Quincy | Illinois | United States | 62301 |
| 29 | Beacon Medical Group Rheumatology Main Street | Granger | Indiana | United States | 46530 |
| 30 | Diagnostic Rheumatology and Research, PC | Indianapolis | Indiana | United States | 46227 |
| 31 | Ochsner Clinic Baton Rouge | Baton Rouge | Louisiana | United States | 70836 |
| 32 | Phase III Clinical Research | Fall River | Massachusetts | United States | 02720 |
| 33 | Clinical Pharmacology Study Group | Worcester | Massachusetts | United States | 01605 |
| 34 | Bronson Internal Medicine and Rheumatology | Battle Creek | Michigan | United States | 49015 |
| 35 | Western Michigan University Homer Stryker MD | Kalamazoo | Michigan | United States | 49007 |
| 36 | North Mississippi Medical Clinics, Inc. - Clinical Research | Tupelo | Mississippi | United States | 38801 |
| 37 | Arthritis & Osteoporosis Associates | Freehold | New Jersey | United States | 07728 |
| 38 | Radnet | Marlton | New Jersey | United States | 08053 |
| 39 | Arthritis, Rheumatic & Back Disease Associates, P.A. | Voorhees | New Jersey | United States | 08043 |
| 40 | Open MRI & Diagnostic Imaging of Wall | Wall | New Jersey | United States | 07719 |
| 41 | AAIR Research Center | Rochester | New York | United States | 14618 |
| 42 | Physicians East, PA | Greenville | North Carolina | United States | 27834 |
| 43 | PMG Research of Salisbury | Salisbury | North Carolina | United States | 28144 |
| 44 | Trinity Health Center-Medical Arts | Minot | North Dakota | United States | 58701 |
| 45 | Group Health Associates | Cincinnati | Ohio | United States | 45236 |
| 46 | Cincinnati Rheumatic Disease Study Group, Inc. | Cincinnati | Ohio | United States | 45242 |
| 47 | STAT Research, Inc. | Dayton | Ohio | United States | 45417 |
| 48 | Health Research of Oklahoma | Oklahoma City | Oklahoma | United States | 73103 |
| 49 | Oklahoma Medical Research Foundation (OMRF) | Oklahoma City | Oklahoma | United States | 73104 |
| 50 | Lynn Health Science Institute | Oklahoma City | Oklahoma | United States | 73112 |
| 51 | East Penn Rheumatology Associates, P.C. | Bethlehem | Pennsylvania | United States | 18015 |
| 52 | Altoona Center for Clinical Research | Duncansville | Pennsylvania | United States | 16635 |
| 53 | Piedmont Arthritis Clinic | Greenville | South Carolina | United States | 29601 |
| 54 | Articularis Healthcare Group dba ACME Research | Orangeburg | South Carolina | United States | 29118 |
| 55 | Articularis Healthcare Group d/b/a Low Country Rheumatology | Summerville | South Carolina | United States | 29486 |
| 56 | Pioneer Research Solutions, Inc. | Cypress | Texas | United States | 77429 |
| 57 | Metroplex Clinical Research Center | Dallas | Texas | United States | 75231 |
| 58 | Center for Arthritis and Rheumatic Diseases | Chesapeake | Virginia | United States | 23320 |
| 59 | Center for Arthritis and Rheumatic Diseases | Suffolk | Virginia | United States | 23435 |
| 60 | Genesis Research Services Pty Ltd | Broadmeadow | New South Wales | Australia | 2292 |
| 61 | Optimus Clinical Research Pty Ltd | Kogarah | New South Wales | Australia | 2217 |
| 62 | Rheumatology Research Unit | Maroochydore | Queensland | Australia | 4558 |
| 63 | Emeritus Research | Melbourne | Victoria | Australia | 3124 |
| 64 | ReumaClinic | Genk | Belgium | 3600 | |
| 65 | AZ Delta | Roeselare | Belgium | 8800 | |
| 66 | University Multiprofile Hospital for Active Treatment Dr. G. Stranski EAD | Pleven | Bulgaria | 5800 | |
| 67 | Multiprofile Hospital for Active Treatment - Plovdiv AD, Rheumatology Department | Plovdiv | Bulgaria | 4000 | |
| 68 | Multiprofile Hospital for Active Treatment Trimontium OOD | Plovdiv | Bulgaria | 4000 | |
| 69 | University Multiprofile Hospital for Active Treatment - Kaspela EOOD | Plovdiv | Bulgaria | 4001 | |
| 70 | National Multiprofile Transport Hospital Tsar Boris III | Sofia | Bulgaria | 1233 | |
| 71 | Medical Centre Synexus Sofia EOOD | Sofia | Bulgaria | 1784 | |
| 72 | CCBR Czech Brno, s.r.o. | Brno | Czech Republic | Czechia | 602 00 |
| 73 | LEKARNA LANCIER s.r.o. | Brno | Czechia | 602 00 | |
| 74 | Lekarna Na Lidicke | Brno | Czechia | 602 00 | |
| 75 | Revmacentrum MUDr. Mostera, s.r.o., Revmatologie a interna | Brno | Czechia | 615 00 | |
| 76 | CCBR Ostrava, s.r.o. | Ostrava | Czechia | 702 00 | |
| 77 | Lekarna Rezidence Nova Karolina | Ostrava | Czechia | 702 00 | |
| 78 | Revmatologicky ustav, Lekrna | Praha 2 | Czechia | 128 50 | |
| 79 | Revmatologicky ustav | Praha 2 | Czechia | 128 50 | |
| 80 | Lekarna Hradebni s.r.o. | Uherske Hradiste | Czechia | 686 01 | |
| 81 | MEDICAL PLUS, s.r.o. Revmatologicka a osteologicka ambulance | Uherske Hradiste | Czechia | 686 01 | |
| 82 | PV - MEDICAL s.r.o., Revmatologicka ambulance | Zlin | Czechia | 760 01 | |
| 83 | Revmavita s.r.o, Lekarna | Zlin | Czechia | 760 01 | |
| 84 | Hamburger Rheuma Forschungszentrum I | Hamburg | Germany | 22391 | |
| 85 | DRC Gyogyszervizsgalo Kozpont Kft. | Balatonfured | Hungary | 8230 | |
| 86 | Revita Rendelo | Budapest | Hungary | 1027 | |
| 87 | Qualiclinic Kft. | Budapest | Hungary | 1036 | |
| 88 | CRU Hungary Kft. | Miskolc | Hungary | 3529 | |
| 89 | Clinical Trial Pharmacy, KyungHee University Hospital | Seoul | Korea, Republic of | 02447 | |
| 90 | KyungHee University Hospital | Seoul | Korea, Republic of | 02447 | |
| 91 | CTC Pharmacy, Seoul National University Hospital | Seoul | Korea, Republic of | 03080 | |
| 92 | Seoul National University Hospital | Seoul | Korea, Republic of | 03080 | |
| 93 | Konkuk University Medical Center | Seoul | Korea, Republic of | 05030 | |
| 94 | Clinical Trial Pharmacy, The Catholic University of Korea, Seoul St. Mary's Hospital | Seoul | Korea, Republic of | 06591 | |
| 95 | The Catholic University of Korea Seoul, St. Mary's Hospital | Seoul | Korea, Republic of | 06591 | |
| 96 | Centro de Investigacion y Tratamiento Reumatologico SC Consultorio Medico de Reumatologia (CINTRE) | Mexico | Ciudad DE Mexico | Mexico | 11850 |
| 97 | Morales Vargas Centro de Investigacion SC (Consultorio Anexo) | Leon | Guanajuato | Mexico | 37000 |
| 98 | Mary Mediatrix Medical Center | Lipa City | Batangas | Philippines | 4217 |
| 99 | Far Eastern University - Nicanor Reyes Medical Foundation, Marian Medical Arts Bldg | Quezon City | Metro Manila | Philippines | 1118 |
| 100 | Zdrowie OSTEO-MEDIC s.c. L i A. Racewicz, A i J. Supronik | Bialystok | Poland | 15-351 | |
| 101 | ClinicMed Daniluk, Nowak. Sp. j. | Bialystok | Poland | 15-879 | |
| 102 | Nzoz Bif - Med | Bytom | Poland | 41-902 | |
| 103 | Centrum Medyczne Pratia Krakow | Krakow | Poland | 30-002 | |
| 104 | Malopolskie Centrum Medyczne S.C. | Krakow | Poland | 30-510 | |
| 105 | NZOZ Lecznica MAK-MED. S.C. | Nadarzyn | Poland | 05-830 | |
| 106 | MTZ Clinical Research Sp. z o.o. | Warszawa | Poland | 02-106 | |
| 107 | Federal State Budgetary Scientific Institution "Research Institute of Rheumatology | Moscow | Russian Federation | 115522 | |
| 108 | FSBEI HE "Orenburg State Medical University" of MoH RF | Orenburg | Russian Federation | 460000 | |
| 109 | FSBEI HE "Orenburg State Medical University" of MoH RF | Orenburg | Russian Federation | 460018 | |
| 110 | SPb SBIH "Consultative-Diagnostic Centre #85" | Saint Petersburg | Russian Federation | 198260 | |
| 111 | FSBIH "Clinical Hospital #122 n.a. L.G. Sokolov" of FMBA of Russia | Saint-Petersburg | Russian Federation | 194291 | |
| 112 | SBIH "Samara Regional Clinical Hospital n.a. V.D. Seredavin" | Samara | Russian Federation | 443095 | |
| 113 | NSHI "Departmental Hospital at Smolensk station OJSC "Russian Railways" | Smolensk | Russian Federation | 214025 | |
| 114 | SAHI YR Clinical Hospital of Emergency Medical Care n.a. N.V. Soloviev | Yaroslavl | Russian Federation | 150003 | |
| 115 | State Budgetary Institution of Healthcare of Yaroslavl Region "Regional Clinical Hospital" | Yaroslavl | Russian Federation | 150062 | |
| 116 | AAGS s.r.o. | Dunajska Streda | Slovakia | 929 01 | |
| 117 | MEDMAN s.r.o. | Martin | Slovakia | 03601 | |
| 118 | REUMACENTRUM s.r.o. | Partizanske | Slovakia | 958 01 | |
| 119 | MUDr. Zuzana Cizmarikova, s.r.o. | Poprad | Slovakia | 05801 | |
| 120 | Reumex s.r.o | Rimavska Sobota | Slovakia | 979 01 | |
| 121 | St. Augustine's Hospital | Durban | Kwazulu Natal | South Africa | 4001 |
| 122 | Complejo Hospitalario Universitario de Santiago | Santiago de Compostela | A Coruna | Spain | 15706 |
| 123 | Hospital Universitario de Cruces | Baracaldo | Vizcaya | Spain | 48903 |
| 124 | Hospital Infanta Luisa | Sevilla | Spain | 41010 | |
| 125 | Countess of Chester Hospital NHS Foundation Trust | Chester | Cheshire | United Kingdom | CH2 1UL |
| 126 | Pharmacy (dispensary) | Chester | Cheshire | United Kingdom | CH2 1UL |
| 127 | Countess of Chester Hospital NHS Foundation Trust | Ellesmere Port | Cheshire | United Kingdom | CH65 6SG |
| 128 | Hampshire Hospitals NHS Foundation Trust | Basingstoke | Hampshire | United Kingdom | RG24 9NA |
| 129 | Pharmacy, Hampshire Hospitals NHS Foundation Trust | Basingstoke | Hampshire | United Kingdom | RG24 9NA |
| 130 | Department of Rheumatology, Wirral University Teaching Hospital NHS Foundation Trust | Wirral | Merseyside | United Kingdom | CH49 5PE |
| 131 | Pharmacy Department, Wirral University Teaching Hospital NHS Foundation Trust | Wirral | Merseyside | United Kingdom | CH49 5PE |
| 132 | Wirral University Teaching Hospital NHS Foundation Trust | Wirral | Merseyside | United Kingdom | CH49 5PE |
| 133 | Pharmacy Department | Dudley | WEST Midlands | United Kingdom | DY1 2HQ |
| 134 | The Dudley Group NHS Foundation Trust | Dudley | WEST Midlands | United Kingdom | DY1 2HQ |
| 135 | Pharmacy | Manchester | United Kingdom | M23 9LT | |
| 136 | University Hospital of South Manchester NHS Foundation Trust | Manchester | United Kingdom | M23 9LT |
Sponsors and Collaborators
- Pfizer
Investigators
- Study Director: Pfizer CT.gov Call Center, Pfizer
Study Documents (Full-Text)
More Information
Additional Information:
Publications
- Burmester GR, Benda B, Gruben D, Bradley J, Mebus C. Tofacitinib for rheumatoid arthritis - Authors' reply. Lancet. 2013 May 25;381(9880):1812-3. doi: 10.1016/S0140-6736(13)61115-0.
- Cella D, Lai JS, Chang CH, Peterman A, Slavin M. Fatigue in cancer patients compared with fatigue in the general United States population. Cancer. 2002 Jan 15;94(2):528-38.
- Felson DT, Smolen JS, Wells G, Zhang B, van Tuyl LH, Funovits J, Aletaha D, Allaart CF, Bathon J, Bombardieri S, Brooks P, Brown A, Matucci-Cerinic M, Choi H, Combe B, de Wit M, Dougados M, Emery P, Furst D, Gomez-Reino J, Hawker G, Keystone E, Khanna D, Kirwan J, Kvien TK, Landewé R, Listing J, Michaud K, Martin-Mola E, Montie P, Pincus T, Richards P, Siegel JN, Simon LS, Sokka T, Strand V, Tugwell P, Tyndall A, van der Heijde D, Verstappen S, White B, Wolfe F, Zink A, Boers M; American College of Rheumatology; European League Against Rheumatism. American College of Rheumatology/European League Against Rheumatism provisional definition of remission in rheumatoid arthritis for clinical trials. Arthritis Rheum. 2011 Mar;63(3):573-86. doi: 10.1002/art.30129.
- Fleischmann R, Cutolo M, Genovese MC, Lee EB, Kanik KS, Sadis S, Connell CA, Gruben D, Krishnaswami S, Wallenstein G, Wilkinson BE, Zwillich SH. Phase IIb dose-ranging study of the oral JAK inhibitor tofacitinib (CP-690,550) or adalimumab monotherapy versus placebo in patients with active rheumatoid arthritis with an inadequate response to disease-modifying antirheumatic drugs. Arthritis Rheum. 2012 Mar;64(3):617-29. doi: 10.1002/art.33383.
- Fleischmann R, Kremer J, Cush J, Schulze-Koops H, Connell CA, Bradley JD, Gruben D, Wallenstein GV, Zwillich SH, Kanik KS; ORAL Solo Investigators. Placebo-controlled trial of tofacitinib monotherapy in rheumatoid arthritis. N Engl J Med. 2012 Aug 9;367(6):495-507. doi: 10.1056/NEJMoa1109071.
- Fries JF, Spitz PW, Young DY. The dimensions of health outcomes: the health assessment questionnaire, disability and pain scales. J Rheumatol. 1982 Sep-Oct;9(5):789-93.
- Hurst NP, Kind P, Ruta D, Hunter M, Stubbings A. Measuring health-related quality of life in rheumatoid arthritis: validity, responsiveness and reliability of EuroQol (EQ-5D). Br J Rheumatol. 1997 May;36(5):551-9.
- Karaman MW, Herrgard S, Treiber DK, Gallant P, Atteridge CE, Campbell BT, Chan KW, Ciceri P, Davis MI, Edeen PT, Faraoni R, Floyd M, Hunt JP, Lockhart DJ, Milanov ZV, Morrison MJ, Pallares G, Patel HK, Pritchard S, Wodicka LM, Zarrinkar PP. A quantitative analysis of kinase inhibitor selectivity. Nat Biotechnol. 2008 Jan;26(1):127-32. doi: 10.1038/nbt1358.
- Kremer J, Li ZG, Hall S, Fleischmann R, Genovese M, Martin-Mola E, Isaacs JD, Gruben D, Wallenstein G, Krishnaswami S, Zwillich SH, Koncz T, Riese R, Bradley J. Tofacitinib in combination with nonbiologic disease-modifying antirheumatic drugs in patients with active rheumatoid arthritis: a randomized trial. Ann Intern Med. 2013 Aug 20;159(4):253-61. doi: 10.7326/0003-4819-159-4-201308200-00006.
- Kremer JM, Cohen S, Wilkinson BE, Connell CA, French JL, Gomez-Reino J, Gruben D, Kanik KS, Krishnaswami S, Pascual-Ramos V, Wallenstein G, Zwillich SH. A phase IIb dose-ranging study of the oral JAK inhibitor tofacitinib (CP-690,550) versus placebo in combination with background methotrexate in patients with active rheumatoid arthritis and an inadequate response to methotrexate alone. Arthritis Rheum. 2012 Apr;64(4):970-81. doi: 10.1002/art.33419. Epub 2011 Oct 17.
- Meyer DM, Jesson MI, Li X, Elrick MM, Funckes-Shippy CL, Warner JD, Gross CJ, Dowty ME, Ramaiah SK, Hirsch JL, Saabye MJ, Barks JL, Kishore N, Morris DL. Anti-inflammatory activity and neutrophil reductions mediated by the JAK1/JAK3 inhibitor, CP-690,550, in rat adjuvant-induced arthritis. J Inflamm (Lond). 2010 Aug 11;7:41. doi: 10.1186/1476-9255-7-41.
- Murray PJ. The JAK-STAT signaling pathway: input and output integration. J Immunol. 2007 Mar 1;178(5):2623-9. Review.
- O'Sullivan LA, Liongue C, Lewis RS, Stephenson SE, Ward AC. Cytokine receptor signaling through the Jak-Stat-Socs pathway in disease. Mol Immunol. 2007 Apr;44(10):2497-506. Epub 2007 Jan 17. Review.
- Reilly MC, Zbrozek AS, Dukes EM. The validity and reproducibility of a work productivity and activity impairment instrument. Pharmacoeconomics. 1993 Nov;4(5):353-65.
- van Vollenhoven RF, Fleischmann R, Cohen S, Lee EB, García Meijide JA, Wagner S, Forejtova S, Zwillich SH, Gruben D, Koncz T, Wallenstein GV, Krishnaswami S, Bradley JD, Wilkinson B; ORAL Standard Investigators. Tofacitinib or adalimumab versus placebo in rheumatoid arthritis. N Engl J Med. 2012 Aug 9;367(6):508-19. doi: 10.1056/NEJMoa1112072. Erratum in: N Engl J Med. 2013 Jul 18;369(3):293.
- Ware JE KM, Dewey JE. . How to score Version 2 of the SF 36 Health Survey (Standard & Acute forms). In: How to score Version 2 of the SF 36 Health Survey (Standard & Acute forms). Lincoln, Rhode Island: QualityMetric, Incorporated. 2000.
Responsible Party:
Pfizer
ClinicalTrials.gov Identifier:
NCT02831855
Other Study ID Numbers:
- A3921192
- 2016-001825-15
First Posted:
Jul 13, 2016
Last Update Posted:
Dec 4, 2019
Last Verified:
Nov 1, 2019
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Keywords provided by Pfizer
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Open Label: Tofacitinib 11 mg + Methotrexate | Double Blind: Tofacitinib 11 mg + Methotrexate Placebo | Double Blind: Tofacitinib 11mg + Methotrexate |
|---|---|---|---|
| Arm/Group Description | 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). | Participants with low disease activity (LDA) at the end of open label phase were randomized to receive Tofacitinib MR 11 mg tablet once daily with matching placebo to blinded methotrexate at their previously stabilized dose for 24 weeks in double blind phase. | Participants with LDA at the end of open label phase were randomized to receive Tofacitinib MR 11 mg tablet once daily with blinded methotrexate at their previously stabilized dose for 24 weeks in double blind phase. |
| Period Title: Open Label Phase (24 Weeks) | |||
| STARTED | 694 | 0 | 0 |
| COMPLETED | 623 | 0 | 0 |
| NOT COMPLETED | 71 | 0 | 0 |
| Period Title: Open Label Phase (24 Weeks) | |||
| STARTED | 0 | 267 | 266 |
| Treated | 0 | 264 | 266 |
| COMPLETED | 0 | 238 | 247 |
| NOT COMPLETED | 0 | 29 | 19 |
Baseline Characteristics
| Arm/Group Title | Open Label: Tofacitinib 11 mg + Methotrexate |
|---|---|
| Arm/Group Description | 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). |
| Overall Participants | 694 |
| Age (Years) [Mean (Standard Deviation) ] | |
| Mean (Standard Deviation) [Years] |
56.77
(11.83)
|
| Sex: Female, Male (Count of Participants) | |
| Female |
532
76.7%
|
| Male |
162
23.3%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |
| Hispanic or Latino |
59
8.5%
|
| Not Hispanic or Latino |
635
91.5%
|
| Unknown or Not Reported |
0
0%
|
| Race/Ethnicity, Customized (Count of Participants) | |
| Asian |
37
5.3%
|
| Black or African American |
33
4.8%
|
| White |
594
85.6%
|
| Others |
30
4.3%
|
Outcome Measures
| Title | 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 |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Double Blind: Tofacitinib 11 mg + Methotrexate Placebo | Double Blind: Tofacitinib 11mg + Methotrexate |
|---|---|---|
| Arm/Group Description | Participants with low disease activity (LDA) at the end of open label phase were randomized to receive Tofacitinib MR 11 mg tablet once daily with matching placebo to blinded methotrexate at their previously stabilized dose for 24 weeks in double blind phase. | Participants with LDA at the end of open label phase were randomized to receive Tofacitinib MR 11 mg tablet once daily with blinded methotrexate at their previously stabilized dose for 24 weeks in double blind phase. |
| Measure Participants | 235 | 237 |
| Least Squares Mean (Standard Error) [units on a scale] |
0.33
(0.07)
|
0.03
(0.07)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Double Blind: Tofacitinib 11 mg + Methotrexate Placebo, Double Blind: Tofacitinib 11mg + Methotrexate |
|---|---|---|
| Comments | 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. | |
| Type of Statistical Test | Non-Inferiority | |
| Comments | Non-inferiority (NI) of Tofacitinib 11 mg + Methotrexate Placebo to Tofacitinib 11 mg + continued Methotrexate was concluded if the upper bound of 95% 2-sided confidence interval (CI) for difference between the 2 arms (Tofacitinib 11 mg + Methotrexate Placebo reporting arm - Tofacitinib 11 mg + continued Methotrexate arm) was lower than 0.6. | |
| Statistical Test of Hypothesis | p-Value | 0.0005 |
| Comments | The p-value is one-sided for the test against the NI margin of 0.6. | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Least Square (LS) Mean Difference |
| Estimated Value | 0.30 | |
| Confidence Interval |
(2-Sided) 95% 0.12 to 0.48 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.09 |
|
| Estimation Comments | ||
| Title | Double Blind Phase: Change From Randomization in DAS28-4 ESR at Week 36 |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Double Blind: Tofacitinib 11 mg + Methotrexate Placebo | Double Blind: Tofacitinib 11mg + Methotrexate |
|---|---|---|
| Arm/Group Description | Participants with low disease activity (LDA) at the end of open label phase were randomized to receive Tofacitinib MR 11 mg tablet once daily with matching placebo to blinded methotrexate at their previously stabilized dose for 24 weeks in double blind phase. | Participants with LDA at the end of open label phase were randomized to receive Tofacitinib MR 11 mg tablet once daily with blinded methotrexate at their previously stabilized dose for 24 weeks in double blind phase. |
| Measure Participants | 253 | 253 |
| Least Squares Mean (Standard Error) [units on a scale] |
0.40
(0.07)
|
0.18
(0.07)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Double Blind: Tofacitinib 11 mg + Methotrexate Placebo, Double Blind: Tofacitinib 11mg + Methotrexate |
|---|---|---|
| Comments | 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. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | 0.22 | |
| Confidence Interval |
(2-Sided) 95% 0.03 to 0.41 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.10 |
|
| Estimation Comments | ||
| Title | Double Blind Phase: Change From Randomization in DAS28-4 (C-reactive Protein [CRP]) at Weeks 36 and 48 |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS-DB was analyzed. Here, 'Number analyzed' = Participants evaluable for this outcome measure at specified time points. |
| Arm/Group Title | Double Blind: Tofacitinib 11 mg + Methotrexate Placebo | Double Blind: Tofacitinib 11mg + Methotrexate |
|---|---|---|
| Arm/Group Description | Participants with low disease activity (LDA) at the end of open label phase were randomized to receive Tofacitinib MR 11 mg tablet once daily with matching placebo to blinded methotrexate at their previously stabilized dose for 24 weeks in double blind phase. | Participants with LDA at the end of open label phase were randomized to receive Tofacitinib MR 11 mg tablet once daily with blinded methotrexate at their previously stabilized dose for 24 weeks in double blind phase. |
| Measure Participants | 264 | 266 |
| Change at Week 36 |
0.38
(0.06)
|
0.13
(0.06)
|
| Change at Week 48 |
0.29
(0.06)
|
0.01
(0.06)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Double Blind: Tofacitinib 11 mg + Methotrexate Placebo, Double Blind: Tofacitinib 11mg + Methotrexate |
|---|---|---|
| Comments | 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. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | 0.26 | |
| Confidence Interval |
(2-Sided) 95% 0.08 to 0.43 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.09 |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Double Blind: Tofacitinib 11 mg + Methotrexate Placebo, Double Blind: Tofacitinib 11mg + Methotrexate |
|---|---|---|
| Comments | 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. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | 0.28 | |
| Confidence Interval |
(2-Sided) 95% 0.11 to 0.45 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.09 |
|
| Estimation Comments | ||
| Title | Double Blind Phase: Change From Randomization in Clinical Disease Activity Index (CDAI) at Weeks 36 and 48 |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS-DB was analyzed. Here, 'Number analyzed' = Participants evaluable for this outcome measure at specified time points. |
| Arm/Group Title | Double Blind: Tofacitinib 11 mg + Methotrexate Placebo | Double Blind: Tofacitinib 11mg + Methotrexate |
|---|---|---|
| Arm/Group Description | Participants with low disease activity (LDA) at the end of open label phase were randomized to receive Tofacitinib MR 11 mg tablet once daily with matching placebo to blinded methotrexate at their previously stabilized dose for 24 weeks in double blind phase. | Participants with LDA at the end of open label phase were randomized to receive Tofacitinib MR 11 mg tablet once daily with blinded methotrexate at their previously stabilized dose for 24 weeks in double blind phase. |
| Measure Participants | 264 | 266 |
| Change at Week 36 |
3.58
(0.49)
|
1.84
(0.48)
|
| Change at Week 48 |
2.97
(0.48)
|
0.84
(0.47)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Double Blind: Tofacitinib 11 mg + Methotrexate Placebo, Double Blind: Tofacitinib 11mg + Methotrexate |
|---|---|---|
| Comments | 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. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | 1.74 | |
| Confidence Interval |
(2-Sided) 95% 0.40 to 3.07 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.68 |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Double Blind: Tofacitinib 11 mg + Methotrexate Placebo, Double Blind: Tofacitinib 11mg + Methotrexate |
|---|---|---|
| Comments | 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. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | 2.13 | |
| Confidence Interval |
(2-Sided) 95% 0.83 to 3.43 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.66 |
|
| Estimation Comments | ||
| Title | Double Blind Phase: Change From Randomization in Simplified Disease Activity Index (SDAI) at Weeks 36 and 48 |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS-DB was analyzed. Here, 'Number analyzed' = Participants evaluable for this outcome measure at specified time points. |
| Arm/Group Title | Double Blind: Tofacitinib 11 mg + Methotrexate Placebo | Double Blind: Tofacitinib 11mg + Methotrexate |
|---|---|---|
| Arm/Group Description | Participants with low disease activity (LDA) at the end of open label phase were randomized to receive Tofacitinib MR 11 mg tablet once daily with matching placebo to blinded methotrexate at their previously stabilized dose for 24 weeks in double blind phase. | Participants with LDA at the end of open label phase were randomized to receive Tofacitinib MR 11 mg tablet once daily with blinded methotrexate at their previously stabilized dose for 24 weeks in double blind phase. |
| Measure Participants | 264 | 266 |
| Change at Week 36 |
3.83
(0.52)
|
1.88
(0.51)
|
| Change at Week 48 |
3.16
(0.50)
|
0.94
(0.49)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Double Blind: Tofacitinib 11 mg + Methotrexate Placebo, Double Blind: Tofacitinib 11mg + Methotrexate |
|---|---|---|
| Comments | 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. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | 1.95 | |
| Confidence Interval |
(2-Sided) 95% 0.53 to 3.37 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.72 |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Double Blind: Tofacitinib 11 mg + Methotrexate Placebo, Double Blind: Tofacitinib 11mg + Methotrexate |
|---|---|---|
| Comments | 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. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | 2.23 | |
| Confidence Interval |
(2-Sided) 95% 0.86 to 3.59 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.69 |
|
| Estimation Comments | ||
| Title | 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 |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Double Blind: Tofacitinib 11 mg + Methotrexate Placebo | Double Blind: Tofacitinib 11mg + Methotrexate |
|---|---|---|
| Arm/Group Description | Participants with low disease activity (LDA) at the end of open label phase were randomized to receive Tofacitinib MR 11 mg tablet once daily with matching placebo to blinded methotrexate at their previously stabilized dose for 24 weeks in double blind phase. | Participants with LDA at the end of open label phase were randomized to receive Tofacitinib MR 11 mg tablet once daily with blinded methotrexate at their previously stabilized dose for 24 weeks in double blind phase. |
| Measure Participants | 264 | 266 |
| Week 36 |
42.42
6.1%
|
48.12
NaN
|
| Week 48 |
45.08
6.5%
|
49.62
NaN
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Double Blind: Tofacitinib 11 mg + Methotrexate Placebo, Double Blind: Tofacitinib 11mg + Methotrexate |
|---|---|---|
| Comments | Week 36 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in percentage of participants |
| Estimated Value | -5.69 | |
| Confidence Interval |
(2-Sided) 95% -14.15 to 2.76 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Double Blind: Tofacitinib 11 mg + Methotrexate Placebo, Double Blind: Tofacitinib 11mg + Methotrexate |
|---|---|---|
| Comments | Week 48 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in percentage of participants |
| Estimated Value | -4.54 | |
| Confidence Interval |
(2-Sided) 95% -13.04 to 3.94 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Double Blind Phase: Percentage of Participants With LDA Assessed by DAS28-4 (CRP) <=3.2 at Weeks 36 and 48 |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Double Blind: Tofacitinib 11 mg + Methotrexate Placebo | Double Blind: Tofacitinib 11mg + Methotrexate |
|---|---|---|
| Arm/Group Description | Participants with low disease activity (LDA) at the end of open label phase were randomized to receive Tofacitinib MR 11 mg tablet once daily with matching placebo to blinded methotrexate at their previously stabilized dose for 24 weeks in double blind phase. | Participants with LDA at the end of open label phase were randomized to receive Tofacitinib MR 11 mg tablet once daily with blinded methotrexate at their previously stabilized dose for 24 weeks in double blind phase. |
| Measure Participants | 264 | 266 |
| Week 36 |
65.53
9.4%
|
70.68
NaN
|
| Week 48 |
65.91
9.5%
|
74.44
NaN
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Double Blind: Tofacitinib 11 mg + Methotrexate Placebo, Double Blind: Tofacitinib 11mg + Methotrexate |
|---|---|---|
| Comments | Week 36 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in percentage of participants |
| Estimated Value | -5.14 | |
| Confidence Interval |
(2-Sided) 95% -13.07 to 2.77 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Double Blind: Tofacitinib 11 mg + Methotrexate Placebo, Double Blind: Tofacitinib 11mg + Methotrexate |
|---|---|---|
| Comments | Week 48 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in percentage of participants |
| Estimated Value | -8.52 | |
| Confidence Interval |
(2-Sided) 95% -16.28 to -0.76 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Double Blind Phase: Percentage of Participants With LDA Assessed by CDAI <=10 at Weeks 36 and 48 |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Double Blind: Tofacitinib 11 mg + Methotrexate Placebo | Double Blind: Tofacitinib 11mg + Methotrexate |
|---|---|---|
| Arm/Group Description | Participants with low disease activity (LDA) at the end of open label phase were randomized to receive Tofacitinib MR 11 mg tablet once daily with matching placebo to blinded methotrexate at their previously stabilized dose for 24 weeks in double blind phase. | Participants with LDA at the end of open label phase were randomized to receive Tofacitinib MR 11 mg tablet once daily with blinded methotrexate at their previously stabilized dose for 24 weeks in double blind phase. |
| Measure Participants | 264 | 266 |
| Week 36 |
66.29
9.6%
|
73.68
NaN
|
| Week 48 |
65.15
9.4%
|
77.07
NaN
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Double Blind: Tofacitinib 11 mg + Methotrexate Placebo, Double Blind: Tofacitinib 11mg + Methotrexate |
|---|---|---|
| Comments | Week 36 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in percentage of participants |
| Estimated Value | -7.39 | |
| Confidence Interval |
(2-Sided) 95% -15.17 to 0.38 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Double Blind: Tofacitinib 11 mg + Methotrexate Placebo, Double Blind: Tofacitinib 11mg + Methotrexate |
|---|---|---|
| Comments | Week 48 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in percentage of participants |
| Estimated Value | -11.91 | |
| Confidence Interval |
(2-Sided) 95% -19.56 to -4.26 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Double Blind Phase: Percentage of Participants With LDA Assessed by SDAI <=11 at Weeks 36 and 48 |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Double Blind: Tofacitinib 11 mg + Methotrexate Placebo | Double Blind: Tofacitinib 11mg + Methotrexate |
|---|---|---|
| Arm/Group Description | Participants with low disease activity (LDA) at the end of open label phase were randomized to receive Tofacitinib MR 11 mg tablet once daily with matching placebo to blinded methotrexate at their previously stabilized dose for 24 weeks in double blind phase. | Participants with LDA at the end of open label phase were randomized to receive Tofacitinib MR 11 mg tablet once daily with blinded methotrexate at their previously stabilized dose for 24 weeks in double blind phase. |
| Measure Participants | 264 | 266 |
| Week 36 |
66.29
9.6%
|
73.31
NaN
|
| Week 48 |
66.29
9.6%
|
76.32
NaN
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Double Blind: Tofacitinib 11 mg + Methotrexate Placebo, Double Blind: Tofacitinib 11mg + Methotrexate |
|---|---|---|
| Comments | Week 36 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in percentage of participants |
| Estimated Value | -7.02 | |
| Confidence Interval |
(2-Sided) 95% -14.81 to 0.77 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Double Blind: Tofacitinib 11 mg + Methotrexate Placebo, Double Blind: Tofacitinib 11mg + Methotrexate |
|---|---|---|
| Comments | Week 48 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in percentage of participants |
| Estimated Value | -10.02 | |
| Confidence Interval |
(2-Sided) 95% -17.68 to -2.37 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | 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 |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Double Blind: Tofacitinib 11 mg + Methotrexate Placebo | Double Blind: Tofacitinib 11mg + Methotrexate |
|---|---|---|
| Arm/Group Description | Participants with low disease activity (LDA) at the end of open label phase were randomized to receive Tofacitinib MR 11 mg tablet once daily with matching placebo to blinded methotrexate at their previously stabilized dose for 24 weeks in double blind phase. | Participants with LDA at the end of open label phase were randomized to receive Tofacitinib MR 11 mg tablet once daily with blinded methotrexate at their previously stabilized dose for 24 weeks in double blind phase. |
| Measure Participants | 264 | 266 |
| Week 36 |
15.53
2.2%
|
24.06
NaN
|
| Week 48 |
22.35
3.2%
|
23.68
NaN
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Double Blind: Tofacitinib 11 mg + Methotrexate Placebo, Double Blind: Tofacitinib 11mg + Methotrexate |
|---|---|---|
| Comments | Week 36 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in percentage of participants |
| Estimated Value | -8.52 | |
| Confidence Interval |
(2-Sided) 95% -15.27 to -1.78 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Double Blind: Tofacitinib 11 mg + Methotrexate Placebo, Double Blind: Tofacitinib 11mg + Methotrexate |
|---|---|---|
| Comments | Week 48 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in percentage of participants |
| Estimated Value | -1.33 | |
| Confidence Interval |
(2-Sided) 95% -8.50 to 5.83 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Double Blind Phase: Percentage of Participants With Remission Assessed by DAS28-4 (ESR) Less Than [<] 2.6 at Weeks 36 and 48 |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Double Blind: Tofacitinib 11 mg + Methotrexate Placebo | Double Blind: Tofacitinib 11mg + Methotrexate |
|---|---|---|
| Arm/Group Description | Participants with low disease activity (LDA) at the end of open label phase were randomized to receive Tofacitinib MR 11 mg tablet once daily with matching placebo to blinded methotrexate at their previously stabilized dose for 24 weeks in double blind phase. | Participants with LDA at the end of open label phase were randomized to receive Tofacitinib MR 11 mg tablet once daily with blinded methotrexate at their previously stabilized dose for 24 weeks in double blind phase. |
| Measure Participants | 264 | 266 |
| Week 36 |
20.45
2.9%
|
28.57
NaN
|
| Week 48 |
23.86
3.4%
|
30.08
NaN
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Double Blind: Tofacitinib 11 mg + Methotrexate Placebo, Double Blind: Tofacitinib 11mg + Methotrexate |
|---|---|---|
| Comments | Week 36 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in percentage of participants |
| Estimated Value | -8.11 | |
| Confidence Interval |
(2-Sided) 95% -15.40 to -0.82 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Double Blind: Tofacitinib 11 mg + Methotrexate Placebo, Double Blind: Tofacitinib 11mg + Methotrexate |
|---|---|---|
| Comments | Week 48 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in percentage of participants |
| Estimated Value | -6.21 | |
| Confidence Interval |
(2-Sided) 95% -13.74 to 1.32 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Double Blind Phase: Percentage of Participants With Remission Assessed by DAS28-4 (CRP) <2.6 at Weeks 36 and 48 |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Double Blind: Tofacitinib 11 mg + Methotrexate Placebo | Double Blind: Tofacitinib 11mg + Methotrexate |
|---|---|---|
| Arm/Group Description | Participants with low disease activity (LDA) at the end of open label phase were randomized to receive Tofacitinib MR 11 mg tablet once daily with matching placebo to blinded methotrexate at their previously stabilized dose for 24 weeks in double blind phase. | Participants with LDA at the end of open label phase were randomized to receive Tofacitinib MR 11 mg tablet once daily with blinded methotrexate at their previously stabilized dose for 24 weeks in double blind phase. |
| Measure Participants | 264 | 266 |
| Week 36 |
50.00
7.2%
|
55.64
NaN
|
| Week 48 |
50.38
7.3%
|
54.51
NaN
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Double Blind: Tofacitinib 11 mg + Methotrexate Placebo, Double Blind: Tofacitinib 11mg + Methotrexate |
|---|---|---|
| Comments | Week 36 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in percentage of participants |
| Estimated Value | -5.63 | |
| Confidence Interval |
(2-Sided) 95% -14.12 to 2.84 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Double Blind: Tofacitinib 11 mg + Methotrexate Placebo, Double Blind: Tofacitinib 11mg + Methotrexate |
|---|---|---|
| Comments | Week 48 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in percentage of participants |
| Estimated Value | -4.13 | |
| Confidence Interval |
(2-Sided) 95% -12.62 to 4.36 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Double Blind Phase: Percentage of Participants With Remission Assessed by CDAI <=2.8 at Weeks 36 and 48 |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Double Blind: Tofacitinib 11 mg + Methotrexate Placebo | Double Blind: Tofacitinib 11mg + Methotrexate |
|---|---|---|
| Arm/Group Description | Participants with low disease activity (LDA) at the end of open label phase were randomized to receive Tofacitinib MR 11 mg tablet once daily with matching placebo to blinded methotrexate at their previously stabilized dose for 24 weeks in double blind phase. | Participants with LDA at the end of open label phase were randomized to receive Tofacitinib MR 11 mg tablet once daily with blinded methotrexate at their previously stabilized dose for 24 weeks in double blind phase. |
| Measure Participants | 264 | 266 |
| Week 36 |
23.48
3.4%
|
32.33
NaN
|
| Week 48 |
28.41
4.1%
|
30.83
NaN
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Double Blind: Tofacitinib 11 mg + Methotrexate Placebo, Double Blind: Tofacitinib 11mg + Methotrexate |
|---|---|---|
| Comments | Week 36 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in percentage of participants |
| Estimated Value | -8.84 | |
| Confidence Interval |
(2-Sided) 95% -16.44 to -1.24 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Double Blind: Tofacitinib 11 mg + Methotrexate Placebo, Double Blind: Tofacitinib 11mg + Methotrexate |
|---|---|---|
| Comments | Week 48 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in percentage of participants |
| Estimated Value | -2.41 | |
| Confidence Interval |
(2-Sided) 95% -10.18 to 5.35 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Double Blind Phase: Percentage of Participants With Remission Assessed by SDAI <=3.3 at Weeks 36 and 48 |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Double Blind: Tofacitinib 11 mg + Methotrexate Placebo | Double Blind: Tofacitinib 11mg + Methotrexate |
|---|---|---|
| Arm/Group Description | Participants with low disease activity (LDA) at the end of open label phase were randomized to receive Tofacitinib MR 11 mg tablet once daily with matching placebo to blinded methotrexate at their previously stabilized dose for 24 weeks in double blind phase. | Participants with LDA at the end of open label phase were randomized to receive Tofacitinib MR 11 mg tablet once daily with blinded methotrexate at their previously stabilized dose for 24 weeks in double blind phase. |
| Measure Participants | 264 | 266 |
| Week 36 |
22.73
3.3%
|
31.58
NaN
|
| Week 48 |
28.79
4.1%
|
31.95
NaN
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Double Blind: Tofacitinib 11 mg + Methotrexate Placebo, Double Blind: Tofacitinib 11mg + Methotrexate |
|---|---|---|
| Comments | Week 36 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in percentage of participants |
| Estimated Value | -8.85 | |
| Confidence Interval |
(2-Sided) 95% -16.38 to -1.31 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Double Blind: Tofacitinib 11 mg + Methotrexate Placebo, Double Blind: Tofacitinib 11mg + Methotrexate |
|---|---|---|
| Comments | Week 48 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in percentage of participants |
| Estimated Value | -3.16 | |
| Confidence Interval |
(2-Sided) 95% -10.99 to 4.65 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Double Blind Phase: Percentage of Participants Achieving an American College of Rheumatology 20 Percent (%) (ACR20) Response at Weeks 36 and 48 |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Double Blind: Tofacitinib 11 mg + Methotrexate Placebo | Double Blind: Tofacitinib 11mg + Methotrexate |
|---|---|---|
| Arm/Group Description | Participants with low disease activity (LDA) at the end of open label phase were randomized to receive Tofacitinib MR 11 mg tablet once daily with matching placebo to blinded methotrexate at their previously stabilized dose for 24 weeks in double blind phase. | Participants with LDA at the end of open label phase were randomized to receive Tofacitinib MR 11 mg tablet once daily with blinded methotrexate at their previously stabilized dose for 24 weeks in double blind phase. |
| Measure Participants | 264 | 266 |
| Week 36 |
73.86
10.6%
|
80.83
NaN
|
| Week 48 |
73.11
10.5%
|
79.70
NaN
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Double Blind: Tofacitinib 11 mg + Methotrexate Placebo, Double Blind: Tofacitinib 11mg + Methotrexate |
|---|---|---|
| Comments | Week 36 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in percentage of participants |
| Estimated Value | -6.96 | |
| Confidence Interval |
(2-Sided) 95% -14.06 to 0.14 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Double Blind: Tofacitinib 11 mg + Methotrexate Placebo, Double Blind: Tofacitinib 11mg + Methotrexate |
|---|---|---|
| Comments | Week 48 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in percentage of participants |
| Estimated Value | -6.59 | |
| Confidence Interval |
(2-Sided) 95% -13.80 to 0.61 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Double Blind Phase: Percentage of Participants Achieving an American College of Rheumatology 50% (ACR50) Response at Weeks 36 and 48 |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Double Blind: Tofacitinib 11 mg + Methotrexate Placebo | Double Blind: Tofacitinib 11mg + Methotrexate |
|---|---|---|
| Arm/Group Description | Participants with low disease activity (LDA) at the end of open label phase were randomized to receive Tofacitinib MR 11 mg tablet once daily with matching placebo to blinded methotrexate at their previously stabilized dose for 24 weeks in double blind phase. | Participants with LDA at the end of open label phase were randomized to receive Tofacitinib MR 11 mg tablet once daily with blinded methotrexate at their previously stabilized dose for 24 weeks in double blind phase. |
| Measure Participants | 264 | 266 |
| Week 36 |
53.79
7.8%
|
66.54
NaN
|
| Week 48 |
55.30
8%
|
67.29
NaN
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Double Blind: Tofacitinib 11 mg + Methotrexate Placebo, Double Blind: Tofacitinib 11mg + Methotrexate |
|---|---|---|
| Comments | Week 36 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in percentage of participants |
| Estimated Value | -12.75 | |
| Confidence Interval |
(2-Sided) 95% -21.01 to -4.48 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Double Blind: Tofacitinib 11 mg + Methotrexate Placebo, Double Blind: Tofacitinib 11mg + Methotrexate |
|---|---|---|
| Comments | Week 48 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in percentage of participants |
| Estimated Value | -11.99 | |
| Confidence Interval |
(2-Sided) 95% -20.22 to -3.75 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Double Blind Phase: Percentage of Participants Achieving an American College of Rheumatology 70% (ACR70) Response at Weeks 36 and 48 |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Double Blind: Tofacitinib 11 mg + Methotrexate Placebo | Double Blind: Tofacitinib 11mg + Methotrexate |
|---|---|---|
| Arm/Group Description | Participants with low disease activity (LDA) at the end of open label phase were randomized to receive Tofacitinib MR 11 mg tablet once daily with matching placebo to blinded methotrexate at their previously stabilized dose for 24 weeks in double blind phase. | Participants with LDA at the end of open label phase were randomized to receive Tofacitinib MR 11 mg tablet once daily with blinded methotrexate at their previously stabilized dose for 24 weeks in double blind phase. |
| Measure Participants | 264 | 266 |
| Week 36 |
35.61
5.1%
|
40.98
NaN
|
| Week 48 |
37.88
5.5%
|
42.86
NaN
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Double Blind: Tofacitinib 11 mg + Methotrexate Placebo, Double Blind: Tofacitinib 11mg + Methotrexate |
|---|---|---|
| Comments | Week 36 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in percentage of participants |
| Estimated Value | -5.37 | |
| Confidence Interval |
(2-Sided) 95% -13.63 to 2.89 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Double Blind: Tofacitinib 11 mg + Methotrexate Placebo, Double Blind: Tofacitinib 11mg + Methotrexate |
|---|---|---|
| Comments | Week 48 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in percentage of participants |
| Estimated Value | -4.97 | |
| Confidence Interval |
(2-Sided) 95% -13.32 to 3.36 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Double Blind Phase: Change From Randomization in Health Assessment Questionnaire-Disability Index (HAQ-DI) at Weeks 36 and 48 |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS-DB was analyzed. Here, 'Number analyzed' = Participants evaluable for this outcome measure at specified time points. |
| Arm/Group Title | Double Blind: Tofacitinib 11 mg + Methotrexate Placebo | Double Blind: Tofacitinib 11mg + Methotrexate |
|---|---|---|
| Arm/Group Description | Participants with low disease activity (LDA) at the end of open label phase were randomized to receive Tofacitinib MR 11 mg tablet once daily with matching placebo to blinded methotrexate at their previously stabilized dose for 24 weeks in double blind phase. | Participants with LDA at the end of open label phase were randomized to receive Tofacitinib MR 11 mg tablet once daily with blinded methotrexate at their previously stabilized dose for 24 weeks in double blind phase. |
| Measure Participants | 264 | 266 |
| Change at Week 36 |
0.10
(0.03)
|
0.01
(0.03)
|
| Change at Week 48 |
0.01
(0.03)
|
0.00
(0.03)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Double Blind: Tofacitinib 11 mg + Methotrexate Placebo, Double Blind: Tofacitinib 11mg + Methotrexate |
|---|---|---|
| Comments | 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. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | 0.09 | |
| Confidence Interval |
(2-Sided) 95% 0.02 to 0.16 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.04 |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Double Blind: Tofacitinib 11 mg + Methotrexate Placebo, Double Blind: Tofacitinib 11mg + Methotrexate |
|---|---|---|
| Comments | 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. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | 0.02 | |
| Confidence Interval |
(2-Sided) 95% -0.06 to 0.09 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.04 |
|
| Estimation Comments | ||
| Title | Double Blind Phase: Change From Randomization in the Short Form 36 (SF-36) Health Survey 8 Domain Scores at Weeks 36 and 48 |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS-DB was analyzed. Here, 'Number analyzed' = Participants evaluable for this outcome measure at specified time points. |
| Arm/Group Title | Double Blind: Tofacitinib 11 mg + Methotrexate Placebo | Double Blind: Tofacitinib 11mg + Methotrexate |
|---|---|---|
| Arm/Group Description | Participants with low disease activity (LDA) at the end of open label phase were randomized to receive Tofacitinib MR 11 mg tablet once daily with matching placebo to blinded methotrexate at their previously stabilized dose for 24 weeks in double blind phase. | Participants with LDA at the end of open label phase were randomized to receive Tofacitinib MR 11 mg tablet once daily with blinded methotrexate at their previously stabilized dose for 24 weeks in double blind phase. |
| Measure Participants | 264 | 266 |
| Change at Week 36: Physical Functioning |
-1.32
(0.50)
|
-0.88
(0.49)
|
| Change at Week 36: Role Physical Score |
-1.69
(0.48)
|
-0.02
(0.47)
|
| Change at Week 36: Social Functioning |
-0.98
(0.50)
|
-0.84
(0.49)
|
| Change at Week 36: Bodily Pain Score |
-2.03
(0.53)
|
-0.58
(0.52)
|
| Change at Week 36: Mental Health Score |
-1.22
(0.51)
|
-0.32
(0.50)
|
| Change at Week 36: Role Emotional Score |
-1.80
(0.56)
|
-0.69
(0.55)
|
| Change at Week 36: Vitality Score |
-1.30
(0.50)
|
-0.15
(0.50)
|
| Change at Week 36: General Health Perception Score |
-0.98
(0.44)
|
-0.87
(0.43)
|
| Change at Week 48: Physical Functioning |
-0.46
(0.49)
|
-0.97
(0.48)
|
| Change at Week 48: Role Physical Score |
-0.88
(0.51)
|
-0.15
(0.50)
|
| Change at Week 48: Social Functioning |
-1.06
(0.53)
|
-0.55
(0.52)
|
| Change at Week 48: Bodily Pain Score |
-1.46
(0.54)
|
-0.71
(0.54)
|
| Change at Week 48: Mental Health Score |
-0.34
(0.54)
|
0.12
(0.54)
|
| Change at Week 48: Role Emotional Score |
-0.83
(0.54)
|
-0.36
(0.54)
|
| Change at Week 48: Vitality Score |
-0.77
(0.52)
|
-0.25
(0.52)
|
| Change at Week 48: General Health Perception Score |
-0.43
(0.45)
|
-1.05
(0.44)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Double Blind: Tofacitinib 11 mg + Methotrexate Placebo, Double Blind: Tofacitinib 11mg + Methotrexate |
|---|---|---|
| Comments | 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. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | -0.44 | |
| Confidence Interval |
(2-Sided) 95% -1.79 to 0.92 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.69 |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Double Blind: Tofacitinib 11 mg + Methotrexate Placebo, Double Blind: Tofacitinib 11mg + Methotrexate |
|---|---|---|
| Comments | 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. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | 0.52 | |
| Confidence Interval |
(2-Sided) 95% -0.82 to 1.85 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.68 |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Double Blind: Tofacitinib 11 mg + Methotrexate Placebo, Double Blind: Tofacitinib 11mg + Methotrexate |
|---|---|---|
| Comments | 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. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | -1.67 | |
| Confidence Interval |
(2-Sided) 95% -2.97 to -0.37 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.66 |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Double Blind: Tofacitinib 11 mg + Methotrexate Placebo, Double Blind: Tofacitinib 11mg + Methotrexate |
|---|---|---|
| Comments | 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. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | -0.73 | |
| Confidence Interval |
(2-Sided) 95% -2.13 to 0.66 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.66 |
|
| Estimation Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Double Blind: Tofacitinib 11 mg + Methotrexate Placebo, Double Blind: Tofacitinib 11mg + Methotrexate |
|---|---|---|
| Comments | 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. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | -0.14 | |
| Confidence Interval |
(2-Sided) 95% -1.50 to 1.21 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.69 |
|
| Estimation Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Double Blind: Tofacitinib 11 mg + Methotrexate Placebo, Double Blind: Tofacitinib 11mg + Methotrexate |
|---|---|---|
| Comments | 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. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | -0.51 | |
| Confidence Interval |
(2-Sided) 95% -1.95 to 0.93 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.73 |
|
| Estimation Comments | ||
Statistical Analysis 7
| Statistical Analysis Overview | Comparison Group Selection | Double Blind: Tofacitinib 11 mg + Methotrexate Placebo, Double Blind: Tofacitinib 11mg + Methotrexate |
|---|---|---|
| Comments | 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. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | -1.45 | |
| Confidence Interval |
(2-Sided) 95% -2.90 to -0.01 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.74 |
|
| Estimation Comments | ||
Statistical Analysis 8
| Statistical Analysis Overview | Comparison Group Selection | Double Blind: Tofacitinib 11 mg + Methotrexate Placebo, Double Blind: Tofacitinib 11mg + Methotrexate |
|---|---|---|
| Comments | 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. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | -0.75 | |
| Confidence Interval |
(2-Sided) 95% -2.23 to 0.73 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.75 |
|
| Estimation Comments | ||
Statistical Analysis 9
| Statistical Analysis Overview | Comparison Group Selection | Double Blind: Tofacitinib 11 mg + Methotrexate Placebo, Double Blind: Tofacitinib 11mg + Methotrexate |
|---|---|---|
| Comments | 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. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | -0.90 | |
| Confidence Interval |
(2-Sided) 95% -2.29 to 0.49 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.71 |
|
| Estimation Comments | ||
Statistical Analysis 10
| Statistical Analysis Overview | Comparison Group Selection | Double Blind: Tofacitinib 11 mg + Methotrexate Placebo, Double Blind: Tofacitinib 11mg + Methotrexate |
|---|---|---|
| Comments | 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. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | -0.46 | |
| Confidence Interval |
(2-Sided) 95% -1.94 to 1.02 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.75 |
|
| Estimation Comments | ||
Statistical Analysis 11
| Statistical Analysis Overview | Comparison Group Selection | Double Blind: Tofacitinib 11 mg + Methotrexate Placebo, Double Blind: Tofacitinib 11mg + Methotrexate |
|---|---|---|
| Comments | 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. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | -1.11 | |
| Confidence Interval |
(2-Sided) 95% -2.64 to 0.43 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.78 |
|
| Estimation Comments | ||
Statistical Analysis 12
| Statistical Analysis Overview | Comparison Group Selection | Double Blind: Tofacitinib 11 mg + Methotrexate Placebo, Double Blind: Tofacitinib 11mg + Methotrexate |
|---|---|---|
| Comments | 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. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | -0.47 | |
| Confidence Interval |
(2-Sided) 95% -1.95 to 1.01 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.75 |
|
| Estimation Comments | ||
Statistical Analysis 13
| Statistical Analysis Overview | Comparison Group Selection | Double Blind: Tofacitinib 11 mg + Methotrexate Placebo, Double Blind: Tofacitinib 11mg + Methotrexate |
|---|---|---|
| Comments | 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. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | -1.15 | |
| Confidence Interval |
(2-Sided) 95% -2.52 to 0.22 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.70 |
|
| Estimation Comments | ||
Statistical Analysis 14
| Statistical Analysis Overview | Comparison Group Selection | Double Blind: Tofacitinib 11 mg + Methotrexate Placebo, Double Blind: Tofacitinib 11mg + Methotrexate |
|---|---|---|
| Comments | 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. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | -0.52 | |
| Confidence Interval |
(2-Sided) 95% -1.94 to 0.91 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.73 |
|
| Estimation Comments | ||
Statistical Analysis 15
| Statistical Analysis Overview | Comparison Group Selection | Double Blind: Tofacitinib 11 mg + Methotrexate Placebo, Double Blind: Tofacitinib 11mg + Methotrexate |
|---|---|---|
| Comments | 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. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | -0.11 | |
| Confidence Interval |
(2-Sided) 95% -1.30 to 1.08 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.61 |
|
| Estimation Comments | ||
Statistical Analysis 16
| Statistical Analysis Overview | Comparison Group Selection | Double Blind: Tofacitinib 11 mg + Methotrexate Placebo, Double Blind: Tofacitinib 11mg + Methotrexate |
|---|---|---|
| Comments | 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. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | 0.62 | |
| Confidence Interval |
(2-Sided) 95% -0.60 to 1.83 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.62 |
|
| Estimation Comments | ||
| Title | Double Blind Phase: Change From Randomization in the SF-36 Health Survey Component Scores at Weeks 36 and 48 |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS-DB was analyzed. Here, 'Number analyzed' = Participants evaluable for this outcome measure at specified time points. |
| Arm/Group Title | Double Blind: Tofacitinib 11 mg + Methotrexate Placebo | Double Blind: Tofacitinib 11mg + Methotrexate |
|---|---|---|
| Arm/Group Description | Participants with low disease activity (LDA) at the end of open label phase were randomized to receive Tofacitinib MR 11 mg tablet once daily with matching placebo to blinded methotrexate at their previously stabilized dose for 24 weeks in double blind phase. | Participants with LDA at the end of open label phase were randomized to receive Tofacitinib MR 11 mg tablet once daily with blinded methotrexate at their previously stabilized dose for 24 weeks in double blind phase. |
| Measure Participants | 264 | 266 |
| Change at Week 36: Physical Component Score |
-1.42
(0.44)
|
-0.60
(0.43)
|
| Change at Week 36: Mental Component Score |
-1.25
(0.48)
|
-0.43
(0.47)
|
| Change at Week 48: Physical Component Score |
-0.83
(0.44)
|
-0.92
(0.43)
|
| Change at Week 48: Mental Component Score |
-0.65
(0.51)
|
0.03
(0.50)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Double Blind: Tofacitinib 11 mg + Methotrexate Placebo, Double Blind: Tofacitinib 11mg + Methotrexate |
|---|---|---|
| Comments | 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. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | -0.82 | |
| Confidence Interval |
(2-Sided) 95% -2.01 to 0.37 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.61 |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Double Blind: Tofacitinib 11 mg + Methotrexate Placebo, Double Blind: Tofacitinib 11mg + Methotrexate |
|---|---|---|
| Comments | 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. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | 0.09 | |
| Confidence Interval |
(2-Sided) 95% -1.11 to 1.29 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.61 |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Double Blind: Tofacitinib 11 mg + Methotrexate Placebo, Double Blind: Tofacitinib 11mg + Methotrexate |
|---|---|---|
| Comments | 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. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | -0.82 | |
| Confidence Interval |
(2-Sided) 95% -2.13 to 0.49 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.67 |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Double Blind: Tofacitinib 11 mg + Methotrexate Placebo, Double Blind: Tofacitinib 11mg + Methotrexate |
|---|---|---|
| Comments | 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. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | -0.68 | |
| Confidence Interval |
(2-Sided) 95% -2.06 to 0.70 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.70 |
|
| Estimation Comments | ||
| Title | Double Blind Phase: Change From Randomization in the Work Productivity and Activity Impairment (WPAI) Scores at Week 36 and 48 |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS-DB was analyzed. Here, 'Number analyzed' = Participants evaluable for this outcome measure at specified time point. |
| Arm/Group Title | Double Blind: Tofacitinib 11 mg + Methotrexate Placebo | Double Blind: Tofacitinib 11mg + Methotrexate |
|---|---|---|
| Arm/Group Description | Participants with low disease activity (LDA) at the end of open label phase were randomized to receive Tofacitinib MR 11 mg tablet once daily with matching placebo to blinded methotrexate at their previously stabilized dose for 24 weeks in double blind phase. | Participants with LDA at the end of open label phase were randomized to receive Tofacitinib MR 11 mg tablet once daily with blinded methotrexate at their previously stabilized dose for 24 weeks in double blind phase. |
| Measure Participants | 264 | 266 |
| Change at Week 36: Absenteeism |
-1.39
(1.79)
|
-3.00
(1.69)
|
| Change at Week 36: Daily activity impairment |
4.00
(1.35)
|
0.81
(1.34)
|
| Change at Week 36: Presenteeism |
3.68
(2.20)
|
0.67
(2.07)
|
| Change at Week 36: Work productivity loss |
3.03
(2.57)
|
0.19
(2.41)
|
| Change at Week 48: Absenteeism |
-2.21
(1.70)
|
-1.69
(1.61)
|
| Change at Week 48: Daily activity impairment |
2.86
(1.47)
|
1.25
(1.46)
|
| Change at Week 48: Presenteeism |
2.82
(2.78)
|
3.72
(2.61)
|
| Change at Week 48: Work productivity loss |
2.98
(3.09)
|
5.45
(2.91)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Double Blind: Tofacitinib 11 mg + Methotrexate Placebo, Double Blind: Tofacitinib 11mg + Methotrexate |
|---|---|---|
| Comments | 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. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | 1.61 | |
| Confidence Interval |
(2-Sided) 95% -3.14 to 6.37 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 2.41 |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Double Blind: Tofacitinib 11 mg + Methotrexate Placebo, Double Blind: Tofacitinib 11mg + Methotrexate |
|---|---|---|
| Comments | 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. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | -0.51 | |
| Confidence Interval |
(2-Sided) 95% -5.01 to 3.99 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 2.28 |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Double Blind: Tofacitinib 11 mg + Methotrexate Placebo, Double Blind: Tofacitinib 11mg + Methotrexate |
|---|---|---|
| Comments | 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. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | 3.19 | |
| Confidence Interval |
(2-Sided) 95% -0.51 to 6.89 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.88 |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Double Blind: Tofacitinib 11 mg + Methotrexate Placebo, Double Blind: Tofacitinib 11mg + Methotrexate |
|---|---|---|
| Comments | 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. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | 1.60 | |
| Confidence Interval |
(2-Sided) 95% -2.41 to 5.61 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 2.04 |
|
| Estimation Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Double Blind: Tofacitinib 11 mg + Methotrexate Placebo, Double Blind: Tofacitinib 11mg + Methotrexate |
|---|---|---|
| Comments | 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. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | 3.01 | |
| Confidence Interval |
(2-Sided) 95% -2.84 to 8.87 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 2.97 |
|
| Estimation Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Double Blind: Tofacitinib 11 mg + Methotrexate Placebo, Double Blind: Tofacitinib 11mg + Methotrexate |
|---|---|---|
| Comments | 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. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | -0.90 | |
| Confidence Interval |
(2-Sided) 95% -8.34 to 6.54 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 3.77 |
|
| Estimation Comments | ||
Statistical Analysis 7
| Statistical Analysis Overview | Comparison Group Selection | Double Blind: Tofacitinib 11 mg + Methotrexate Placebo, Double Blind: Tofacitinib 11mg + Methotrexate |
|---|---|---|
| Comments | 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. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | 2.84 | |
| Confidence Interval |
(2-Sided) 95% -3.97 to 9.65 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 3.45 |
|
| Estimation Comments | ||
Statistical Analysis 8
| Statistical Analysis Overview | Comparison Group Selection | Double Blind: Tofacitinib 11 mg + Methotrexate Placebo, Double Blind: Tofacitinib 11mg + Methotrexate |
|---|---|---|
| Comments | 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. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | -2.46 | |
| Confidence Interval |
(2-Sided) 95% -10.72 to 5.80 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 4.19 |
|
| Estimation Comments | ||
| Title | Double Blind Phase: Change From Randomization in the European Quality of Life - 5 Dimensions Questionnaire (EQ-5D) Scores at Weeks 36 and 48 |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS-DB population was analyzed. Here, 'Number analyzed' = Participants evaluable for this outcome measure for specified time points. |
| Arm/Group Title | Double Blind: Tofacitinib 11 mg + Methotrexate Placebo | Double Blind: Tofacitinib 11mg + Methotrexate |
|---|---|---|
| Arm/Group Description | Participants with low disease activity (LDA) at the end of open label phase were randomized to receive Tofacitinib MR 11 mg tablet once daily with matching placebo to blinded methotrexate at their previously stabilized dose for 24 weeks in double blind phase. | Participants with LDA at the end of open label phase were randomized to receive Tofacitinib MR 11 mg tablet once daily with blinded methotrexate at their previously stabilized dose for 24 weeks in double blind phase. |
| Measure Participants | 264 | 266 |
| Change at Week 36 |
-0.05
(0.01)
|
-0.01
(0.01)
|
| Change at Week 48 |
-0.02
(0.01)
|
0.00
(0.01)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Double Blind: Tofacitinib 11 mg + Methotrexate Placebo, Double Blind: Tofacitinib 11mg + Methotrexate |
|---|---|---|
| Comments | 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. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | -0.04 | |
| Confidence Interval |
(2-Sided) 95% -0.07 to -0.01 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.02 |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Double Blind: Tofacitinib 11 mg + Methotrexate Placebo, Double Blind: Tofacitinib 11mg + Methotrexate |
|---|---|---|
| Comments | 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. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | -0.03 | |
| Confidence Interval |
(2-Sided) 95% -0.06 to 0.01 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.02 |
|
| Estimation Comments | ||
| Title | Double Blind Phase: Change From Randomization in the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scale Scores at Weeks 36 and 48 |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS-DB population was analyzed. Here, 'Number analyzed' = Participants evaluable for this outcome measure for specified time points. |
| Arm/Group Title | Double Blind: Tofacitinib 11 mg + Methotrexate Placebo | Double Blind: Tofacitinib 11mg + Methotrexate |
|---|---|---|
| Arm/Group Description | Participants with low disease activity (LDA) at the end of open label phase were randomized to receive Tofacitinib MR 11 mg tablet once daily with matching placebo to blinded methotrexate at their previously stabilized dose for 24 weeks in double blind phase. | Participants with LDA at the end of open label phase were randomized to receive Tofacitinib MR 11 mg tablet once daily with blinded methotrexate at their previously stabilized dose for 24 weeks in double blind phase. |
| Measure Participants | 264 | 266 |
| Change at Week 36 |
-0.99
(0.43)
|
-0.80
(0.43)
|
| Change at Week 48 |
-0.34
(0.46)
|
-0.52
(0.45)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Double Blind: Tofacitinib 11 mg + Methotrexate Placebo, Double Blind: Tofacitinib 11mg + Methotrexate |
|---|---|---|
| Comments | 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. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | -0.19 | |
| Confidence Interval |
(2-Sided) 95% -1.37 to 1.00 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.60 |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Double Blind: Tofacitinib 11 mg + Methotrexate Placebo, Double Blind: Tofacitinib 11mg + Methotrexate |
|---|---|---|
| Comments | 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. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | 0.18 | |
| Confidence Interval |
(2-Sided) 95% -1.07 to 1.44 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.64 |
|
| Estimation Comments | ||
| Title | Double Blind Phase: Percentage of Participants Achieving an Improvement of at Least 0.22 Units in HAQ-DI at Weeks 36 and 48 |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Double Blind: Tofacitinib 11 mg + Methotrexate Placebo | Double Blind: Tofacitinib 11mg + Methotrexate |
|---|---|---|
| Arm/Group Description | Participants with low disease activity (LDA) at the end of open label phase were randomized to receive Tofacitinib MR 11 mg tablet once daily with matching placebo to blinded methotrexate at their previously stabilized dose for 24 weeks in double blind phase. | Participants with LDA at the end of open label phase were randomized to receive Tofacitinib MR 11 mg tablet once daily with blinded methotrexate at their previously stabilized dose for 24 weeks in double blind phase. |
| Measure Participants | 264 | 266 |
| Week 36 |
67.05
9.7%
|
77.07
NaN
|
| Week 48 |
68.56
9.9%
|
75.19
NaN
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Double Blind: Tofacitinib 11 mg + Methotrexate Placebo, Double Blind: Tofacitinib 11mg + Methotrexate |
|---|---|---|
| Comments | Week 36 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in percentage of participants |
| Estimated Value | -10.02 | |
| Confidence Interval |
(2-Sided) 95% -17.61 to -2.42 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 3.87 |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Double Blind: Tofacitinib 11 mg + Methotrexate Placebo, Double Blind: Tofacitinib 11mg + Methotrexate |
|---|---|---|
| Comments | Week 48 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in percentage of participants |
| Estimated Value | -6.62 | |
| Confidence Interval |
(2-Sided) 95% -14.26 to 1.00 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 3.89 |
|
| Estimation Comments | ||
| Title | Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious AEs |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Overall study safety analysis set included all participants who received at least one dose of study drug during the study. |
| Arm/Group Title | Open Label: Tofacitinib 11 mg + Methotrexate | Double Blind: Tofacitinib 11 mg + Methotrexate Placebo | Double Blind: Tofacitinib 11mg + Methotrexate |
|---|---|---|---|
| Arm/Group Description | 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). | Participants with low disease activity (LDA) at the end of open label phase were randomized to receive Tofacitinib MR 11 mg tablet once daily with matching placebo to blinded methotrexate at their previously stabilized dose for 24 weeks in double blind phase. | Participants with LDA at the end of open label phase were randomized to receive Tofacitinib MR 11 mg tablet once daily with blinded methotrexate at their previously stabilized dose for 24 weeks in double blind phase. |
| Measure Participants | 694 | 264 | 266 |
| AEs |
362
52.2%
|
107
NaN
|
109
NaN
|
| SAEs |
20
2.9%
|
10
NaN
|
5
NaN
|
| Title | Number of Participants With Abnormal Laboratory Parameters |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Open Label: Tofacitinib 11 mg + Methotrexate | Double Blind: Tofacitinib 11 mg + Methotrexate Placebo | Double Blind: Tofacitinib 11mg + Methotrexate |
|---|---|---|---|
| Arm/Group Description | 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). | Participants with low disease activity (LDA) at the end of open label phase were randomized to receive Tofacitinib MR 11 mg tablet once daily with matching placebo to blinded methotrexate at their previously stabilized dose for 24 weeks in double blind phase. | Participants with LDA at the end of open label phase were randomized to receive Tofacitinib MR 11 mg tablet once daily with blinded methotrexate at their previously stabilized dose for 24 weeks in double blind phase. |
| Measure Participants | 688 | 263 | 263 |
| Count of Participants [Participants] |
682
98.3%
|
263
NaN
|
263
NaN
|
Adverse Events
| Time Frame | Baseline (Day 1) up to Week 52 | |||||
|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. AEs were evaluated for participants with at least 1 dose of the study drug during the study. | |||||
| Arm/Group Title | Open Label: Tofacitinib 11 mg + Methotrexate | Double Blind: Tofacitinib 11 mg + Methotrexate Placebo | Double Blind: Tofacitinib 11mg + Methotrexate | |||
| Arm/Group Description | 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). | Participants with low disease activity (LDA) at the end of open label phase were randomized to receive Tofacitinib MR 11 mg tablet once daily with matching placebo to blinded methotrexate at their previously stabilized dose for 24 weeks in double blind phase. | Participants with LDA at the end of open label phase were randomized to receive Tofacitinib MR 11 mg tablet once daily with blinded methotrexate at their previously stabilized dose for 24 weeks in double blind phase. | |||
All Cause Mortality |
||||||
| Open Label: Tofacitinib 11 mg + Methotrexate | Double Blind: Tofacitinib 11 mg + Methotrexate Placebo | Double Blind: Tofacitinib 11mg + Methotrexate | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/694 (0%) | 0/264 (0%) | 2/266 (0.8%) | |||
Serious Adverse Events |
||||||
| Open Label: Tofacitinib 11 mg + Methotrexate | Double Blind: Tofacitinib 11 mg + Methotrexate Placebo | Double Blind: Tofacitinib 11mg + Methotrexate | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 20/694 (2.9%) | 10/264 (3.8%) | 5/266 (1.9%) | |||
| Cardiac disorders | ||||||
| Angina unstable | 1/694 (0.1%) | 0/264 (0%) | 0/266 (0%) | |||
| Atrial fibrillation | 1/694 (0.1%) | 0/264 (0%) | 0/266 (0%) | |||
| Gastrointestinal disorders | ||||||
| Umbilical hernia | 0/694 (0%) | 1/264 (0.4%) | 0/266 (0%) | |||
| Hiatus hernia | 1/694 (0.1%) | 0/264 (0%) | 0/266 (0%) | |||
| Pancreatitis acute | 1/694 (0.1%) | 0/264 (0%) | 0/266 (0%) | |||
| Peritoneal disorder | 1/694 (0.1%) | 0/264 (0%) | 0/266 (0%) | |||
| Hepatobiliary disorders | ||||||
| Bile duct stone | 1/694 (0.1%) | 0/264 (0%) | 0/266 (0%) | |||
| Gallbladder disorder | 1/694 (0.1%) | 0/264 (0%) | 0/266 (0%) | |||
| Infections and infestations | ||||||
| Encephalitis viral | 0/694 (0%) | 0/264 (0%) | 1/266 (0.4%) | |||
| Infective exacerbation of chronic obstructive airways disease | 0/694 (0%) | 0/264 (0%) | 1/266 (0.4%) | |||
| Osteomyelitis | 0/694 (0%) | 1/264 (0.4%) | 0/266 (0%) | |||
| Pneumonia | 3/694 (0.4%) | 1/264 (0.4%) | 0/266 (0%) | |||
| Influenza | 1/694 (0.1%) | 0/264 (0%) | 0/266 (0%) | |||
| Respiratory tract infection | 1/694 (0.1%) | 0/264 (0%) | 0/266 (0%) | |||
| Injury, poisoning and procedural complications | ||||||
| Femur fracture | 1/694 (0.1%) | 1/264 (0.4%) | 0/266 (0%) | |||
| Spinal compression fracture | 0/694 (0%) | 1/264 (0.4%) | 0/266 (0%) | |||
| Fall | 1/694 (0.1%) | 0/264 (0%) | 0/266 (0%) | |||
| Hip fracture | 1/694 (0.1%) | 0/264 (0%) | 0/266 (0%) | |||
| Patella fracture | 1/694 (0.1%) | 0/264 (0%) | 0/266 (0%) | |||
| Tibia fracture | 1/694 (0.1%) | 0/264 (0%) | 0/266 (0%) | |||
| Investigations | ||||||
| Blood pressure increased | 1/694 (0.1%) | 0/264 (0%) | 0/266 (0%) | |||
| Metabolism and nutrition disorders | ||||||
| Dehydration | 1/694 (0.1%) | 0/264 (0%) | 0/266 (0%) | |||
| Musculoskeletal and connective tissue disorders | ||||||
| Mobility decreased | 0/694 (0%) | 1/264 (0.4%) | 0/266 (0%) | |||
| Osteoarthritis | 0/694 (0%) | 0/264 (0%) | 1/266 (0.4%) | |||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||
| Adrenal adenoma | 0/694 (0%) | 1/264 (0.4%) | 0/266 (0%) | |||
| Glioblastoma | 0/694 (0%) | 1/264 (0.4%) | 0/266 (0%) | |||
| Papillary thyroid cancer | 1/694 (0.1%) | 0/264 (0%) | 0/266 (0%) | |||
| Prostate cancer | 1/694 (0.1%) | 0/264 (0%) | 0/266 (0%) | |||
| Thyroid cancer metastatic | 1/694 (0.1%) | 0/264 (0%) | 0/266 (0%) | |||
| Nervous system disorders | ||||||
| Nerve root compression | 0/694 (0%) | 1/264 (0.4%) | 0/266 (0%) | |||
| Renal and urinary disorders | ||||||
| Renal colic | 0/694 (0%) | 1/264 (0.4%) | 0/266 (0%) | |||
| Nephrolithiasis | 1/694 (0.1%) | 0/264 (0%) | 0/266 (0%) | |||
| Reproductive system and breast disorders | ||||||
| Cervical dysplasia | 1/694 (0.1%) | 0/264 (0%) | 0/266 (0%) | |||
| Respiratory, thoracic and mediastinal disorders | ||||||
| Asthma | 1/694 (0.1%) | 1/264 (0.4%) | 0/266 (0%) | |||
| Pulmonary embolism | 0/694 (0%) | 1/264 (0.4%) | 2/266 (0.8%) | |||
| Bronchitis chronic | 1/694 (0.1%) | 0/264 (0%) | 0/266 (0%) | |||
| Interstitial lung disease | 1/694 (0.1%) | 0/264 (0%) | 0/266 (0%) | |||
Other (Not Including Serious) Adverse Events |
||||||
| Open Label: Tofacitinib 11 mg + Methotrexate | Double Blind: Tofacitinib 11 mg + Methotrexate Placebo | Double Blind: Tofacitinib 11mg + Methotrexate | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 158/694 (22.8%) | 24/264 (9.1%) | 31/266 (11.7%) | |||
| Gastrointestinal disorders | ||||||
| Diarrhoea | 16/694 (2.3%) | 0/264 (0%) | 0/266 (0%) | |||
| Nausea | 20/694 (2.9%) | 0/264 (0%) | 0/266 (0%) | |||
| Infections and infestations | ||||||
| Bronchitis | 0/694 (0%) | 3/264 (1.1%) | 7/266 (2.6%) | |||
| Nasopharyngitis | 35/694 (5%) | 5/264 (1.9%) | 7/266 (2.6%) | |||
| Upper respiratory tract infection | 33/694 (4.8%) | 4/264 (1.5%) | 6/266 (2.3%) | |||
| Urinary tract infection | 19/694 (2.7%) | 0/264 (0%) | 0/266 (0%) | |||
| Investigations | ||||||
| Alanine aminotransferase increased | 16/694 (2.3%) | 5/264 (1.9%) | 10/266 (3.8%) | |||
| Aspartate aminotransferase increased | 0/694 (0%) | 5/264 (1.9%) | 6/266 (2.3%) | |||
| Musculoskeletal and connective tissue disorders | ||||||
| Arthralgia | 0/694 (0%) | 7/264 (2.7%) | 2/266 (0.8%) | |||
| Nervous system disorders | ||||||
| Headache | 17/694 (2.4%) | 0/264 (0%) | 0/266 (0%) | |||
| Dizziness | 15/694 (2.2%) | 0/264 (0%) | 0/266 (0%) | |||
| Vascular disorders | ||||||
| Hypertension | 17/694 (2.4%) | 0/264 (0%) | 0/266 (0%) | |||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
Results Point of Contact
| Name/Title | Pfizer ClinicalTrials.gov Call Center |
|---|---|
| Organization | Pfizer Inc. |
| Phone | 1-800-718-1021 |
| ClinicalTrials.gov_Inquiries@pfizer.com |
Responsible Party:
Pfizer
ClinicalTrials.gov Identifier:
NCT02831855
Other Study ID Numbers:
- A3921192
- 2016-001825-15
First Posted:
Jul 13, 2016
Last Update Posted:
Dec 4, 2019
Last Verified:
Nov 1, 2019