A Phase 4 interventional study of CP-690,550 and Methotrexate in Rheumatoid Arthritis, sponsored by Pfizer. Completed at 136 sites in 16 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2019-12-04.
Sponsored by Pfizer · Phase 4, Interventional, and Treatment
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.
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Key Inclusion Criteria
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.
Key Exclusion Criteria
Open-label tofacitinib tablet and blinded methotrexate capsule
Drug: CP-690,550 · Drug: Methotrexate
open-label tofacitinib tablet and blinded matching placebo for methotrexate capsule
Drug: Placebo
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.
Also known as: tofacitinib
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.
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.
Double Blind Phase: Change From Randomization in Disease Activity Score in 28 Joints Using 4 Variables (DAS28-4) (Erythrocyte Sedimentation Rate [ESR]) at Week 48
DAS28 is a measure of disease activity in participants with rheumatoid arthritis. DAS28-4 (ESR) was calculated from swollen joint count (SJC) and tender/painful joint count (TJC) using 28 joints count, ESR (millimeters per hour \[mm/hr\]) and participant global assessment of arthritis (PtGA) on a 100 millimeter (mm) visual analog scale (VAS: scores ranging from 0 mm \[very well\] to 100 mm \[worst\], higher scores indicate worse health condition). Total DAS28-4 (ESR) score range: 0 (none) to 9.4 (extreme disease activity), higher score indicated more disease activity. DAS28-4 (ESR) less than or equal to (\<=) 3.2 implied low disease activity and greater than (\>) 3.2 to \<=5.1 implied moderate disease activity, \>5.1 implied high disease activity, and DAS28-4 (ESR) less than (\<) 2.6 implied remission. DAS28-4 (ESR) = 0.56\*sqrt(TJC28) + 0.28\*sqrt(SJC28) + 0.70\*In(ESR in mm/hour) + 0.014\*PtGA in mm; ln = natural logarithm, sqrt = square root of.
Time frame: Randomization (last non-missing measurement on or prior to the first dosing date in DB phase at Week 24), Week 48
Double Blind Phase: Change From Randomization in DAS28-4 ESR at Week 36
DAS28 is a measure of disease activity in participants with rheumatoid arthritis. DAS28-4 (ESR) was calculated from SJC and TJC using 28 joints count, ESR (mm/hr) and PtGA on a 100 millimeter (mm) VAS (VAS: scores ranging from 0 mm \[very well\] to 100 mm \[worst\], higher scores indicate worse health condition). Total DAS28-4 (ESR) score range: 0 (none) to 9.4 (extreme disease activity), higher score indicated more disease activity. DAS28-4 (ESR) less than or equal to (\<=) 3.2 implied low disease activity and greater than (\>) 3.2 to \<=5.1 implied moderate disease activity, \>5.1 implied high disease activity, and DAS28-4 (ESR) less than (\<) 2.6 implied remission. DAS28-4 (ESR) = 0.56\*sqrt(TJC28) + 0.28\*sqrt(SJC28) + 0.70\*In(ESR in mm/hour) + 0.014\*PtGA in mm; ln = natural logarithm, sqrt = square root of.
Time frame: Randomization (last non-missing measurement on or prior to the first dosing date in DB phase at Week 24), Week 36
Double Blind Phase: Change From Randomization in DAS28-4 (C-reactive Protein [CRP]) at Weeks 36 and 48
DAS28 is a measure of disease activity in participants with rheumatoid arthritis. DAS28-4 (CRP) was calculated from SJC and TJC using 28 joints count, CRP (milligrams per liter \[mg/L\]) and PtGA on a 100 mm VAS (VAS: scores ranging from 0 mm \[very well\] to 100 mm \[worst\], higher scores indicate worse health condition). Total DAS28-4 (CRP) score range: 0 (none) to 9.4 (extreme disease activity), higher score indicated more disease activity. DAS28-4 (CRP) \<= 3.2 implied low disease activity and \> 3.2 to \<=5.1 implied moderate disease activity, \>5.1 implied high disease activity, and DAS28-4 (CRP) \< 2.6 implied remission. DAS28-4 (CRP) = 0.56\*sqrt(TJC28) + 0.28\*sqrt(SJC28) + 0.36\*ln(CRP in mg/L +1) + 0.014\*PtGA in mm+ 0.96; ln = natural logarithm, sqrt = square root of.
Time frame: Randomization (last non-missing measurement on or prior to the first dosing date in DB phase at Week 24), Weeks 36 and 48
Double Blind Phase: Change From Randomization in Clinical Disease Activity Index (CDAI) at Weeks 36 and 48
CDAI was calculated from tender and swollen joints using 28 joint count, PtGA and physician global assessment of arthritis (PhyGA). PtGA and PhyGA both were assessed on 0-10 centimeter (cm) VAS scale (VAS: scores ranging from 0 cm \[very well\] to 10 cm \[worst\]), where higher scores indicated greater affliction due to disease activity). CDAI total score ranged from 0 to 76, where higher scores indicated higher disease activity. CDAI score of \<=10 indicated low disease activity and a score of \<= 2.8 indicated remission. CDAI = (28TJC) + (28SJC) + (PhyGA in cm) + (PtGA in cm).
Time frame: Randomization (last non-missing measurement on or prior to the first dosing date in DB phase at Week 24), Weeks 36 and 48
Double Blind Phase: Change From Randomization in Simplified Disease Activity Index (SDAI) at Weeks 36 and 48
SDAI was calculated from tender and swollen joints using 28 joint count, PtGA, PhyGA and CRP (in mg/dL). PtGA and PhyGA both were assessed on 0-10 cm VAS scale (VAS: scores ranging from 0 cm \[very well\] to 10 cm \[worst\]), where higher scores indicated greater affliction due to disease activity). SDAI total score ranged from 0 to 86, where higher scores indicated higher disease activity. SDAI score of \<=11 indicates low disease activity and a score of \<=3.3 indicates remission. SDAI = (28TJC) + (28SJC) + (PhyGA in cm) + (PtGA in cm) + (CRP in mg/dL).
Time frame: Randomization (last non-missing measurement on or prior to the first dosing date in DB phase at Week 24), Weeks 36 and 48
Double Blind Phase: Percentage of Participants With Low Disease Activity (LDA) Assessed by DAS28-4 (ESR) Less Than or Equal to (<=) 3.2 at Weeks 36 and 48
DAS28 is a measure of disease activity in participants with rheumatoid arthritis. DAS28-4 (ESR) was calculated from SJC and TJC using 28 joints count, ESR (mm/hr) and PtGA on a 100 mm VAS (VAS: scores ranging from 0 mm \[very well\] to 100 mm \[worst\], higher scores indicated worse health condition). Total DAS28-4 (ESR) score range: 0 (none) to 9.4 (extreme disease activity), higher score indicated more disease activity. DAS28-4 (ESR) \<=3.2 implied low disease activity and \>3.2 to \<=5.1 implied moderate disease activity, \>5.1 implied high disease activity, and DAS28-4 (ESR) \<2.6 implied remission. DAS28-4 (ESR) = 0.56\*sqrt(TJC28) + 0.28\*sqrt(SJC28) + 0.70\*In(ESR in mm/hour) + 0.014\*PtGA in mm; ln = natural logarithm, sqrt = square root of.
Time frame: Weeks 36 and 48
Double Blind Phase: Percentage of Participants With LDA Assessed by DAS28-4 (CRP) <=3.2 at Weeks 36 and 48
DAS28 is a measure of disease activity in participants with rheumatoid arthritis. DAS28-4 (CRP) was calculated from SJC and TJC using 28 joints count, CRP (mg/L) and PtGA on a 100 mm VAS (VAS: scores ranging from 0 mm \[very well\] to 100 mm \[worst\], higher scores indicate worse health condition). Total DAS28-4 (CRP) score range: 0 (none) to 9.4 (extreme disease activity), higher score indicated more disease activity. DAS28-4 (CRP) \<=3.2 implied low disease activity and \>3.2 to \<=5.1 implied moderate disease activity, \>5.1 implied high disease activity, and DAS28-4 (CRP) \<2.6 implied remission. DAS28-4 (CRP) = 0.56\*sqrt(TJC28) + 0.28\*sqrt(SJC28) + 0.36\*ln(CRP in mg/L +1) + 0.014\*PtGA in mm+ 0.96; ln = natural logarithm, sqrt = square root of.
Time frame: Weeks 36 and 48
Double Blind Phase: Percentage of Participants With LDA Assessed by CDAI <=10 at Weeks 36 and 48
CDAI was calculated from tender and swollen joints using 28 joint count, PtGA and PhyGA. PtGA and PhyGA both were assessed on 0-10 cm VAS scale (VAS: scores ranging from 0 cm \[very well\] to 10 cm \[worst\]), where higher scores indicated greater affliction due to disease activity). CDAI total score ranged from 0 to 76, where higher scores indicated higher disease activity. CDAI score of \<=10 indicated low disease activity and a score of \<= 2.8 indicated remission. Percentage of participants with CDAI \<=10 were reported. CDAI = (28TJC) + (28SJC) + (PhyGA in cm) + (PtGA in cm).
Time frame: Weeks 36 and 48
Double Blind Phase: Percentage of Participants With LDA Assessed by SDAI <=11 at Weeks 36 and 48
SDAI was calculated from tender and swollen joints using 28 joint count, PtGA, PhyGA and CRP (in mg/dL). PtGA and PhyGA both were assessed on 0-10 cm VAS scale (VAS: scores ranging from 0 cm \[very well\] to 10 cm \[worst\]), where higher scores indicated greater affliction due to disease activity). SDAI total score ranged from 0 to 86, where higher scores indicated higher disease activity. SDAI score of \<=11 indicated low disease activity and a score of \<=3.3 indicated remission. SDAI = (28TJC) + (28SJC) + (PhyGA in cm) + (PtGA in cm) + (CRP in mg/dL).
Time frame: Weeks 36 and 48
Double Blind Phase: Percentage of Participants With Remission Assessed by American College of Rheumatology-European League Against Rheumatism (ACR-EULAR) Boolean at Weeks 36 and 48
ACR-EULAR Boolean remission was when a participant satisfied all of the following: tender joint count, swollen joint count (both based on a 28-joint assessment), CRP (in mg/dL), and PtGA (VAS: 0 cm \[very well\] to 10 cm \[worst\], higher scores indicated worse health condition) and all scores were \<=1.
Time frame: Weeks 36 and 48
Double Blind Phase: Percentage of Participants With Remission Assessed by DAS28-4 (ESR) Less Than [<] 2.6 at Weeks 36 and 48
DAS28 is a measure of disease activity in participants with rheumatoid arthritis. DAS28-4 (ESR) was calculated from SJC and TJC using 28 joints count, ESR (mm/hr) and PtGA on a 100 mm VAS (VAS: scores ranging from 0 mm \[very well\] to 100 mm \[worst\], higher scores indicate worse health condition). Total DAS28-4 (ESR) score range: 0 (none) to 9.4 (extreme disease activity), higher score indicated more disease activity. DAS28-4 (ESR) \<= 3.2 implied low disease activity and \>3.2 to \<=5.1 implied moderate disease activity, \>5.1 implied high disease activity, and DAS28-4 (ESR) \<2.6 implied remission. DAS28-4 (ESR) = 0.56\*sqrt(TJC28) + 0.28\*sqrt(SJC28) + 0.70\*In(ESR in mm/hour) + 0.014\*PtGA in mm. Percentage of participants with DAS remission (DAS28-4-ESR\<2.6) were reported in this outcome measure.
Time frame: Weeks 36 and 48
Double Blind Phase: Percentage of Participants With Remission Assessed by DAS28-4 (CRP) <2.6 at Weeks 36 and 48
DAS28 is a measure of disease activity in participants with rheumatoid arthritis. DAS28-4 (CRP) was calculated from SJC and TJC using 28 joints count, CRP (mg/L) and PtGA on a 100 mm VAS (VAS: scores ranging from 0 mm \[very well\] to 100 mm \[worst\], higher scores indicate worse health condition). Total DAS28-4 (CRP) score range: 0 (none) to 9.4 (extreme disease activity), higher score indicated more disease activity. DAS28-4 (CRP) \<=3.2 implied low disease activity and \>3.2 to \<=5.1 implied moderate disease activity, \>5.1 implied high disease activity, and DAS28-4 (CRP) \<2.6 implied remission. DAS28-4 (CRP) = 0.56\*sqrt(TJC28) + 0.28\*sqrt(SJC28) + 0.36\*ln(CRP in mg/l +1) + 0.014\*PtGA in mm+ 0.96. Percentage of participants with DAS remission (DAS28-4-CRP\<2.6) were reported in this outcome measure.
Time frame: Weeks 36 and 48
Double Blind Phase: Percentage of Participants With Remission Assessed by CDAI <=2.8 at Weeks 36 and 48
CDAI was calculated from tender and swollen joints using 28 joint count, PtGA and PhyGA. PtGA and PhyGA both were assessed on 0-10 cm VAS scale (VAS: scores ranging from 0 cm \[very well\] to 10 cm \[worst\]), where higher scores indicated greater affliction due to disease activity). CDAI total score ranged from 0 to 76, where higher scores indicated higher disease activity. CDAI score of \<=10 indicated low disease activity and a score of \<= 2.8 indicated remission. CDAI = (28TJC) + (28SJC) + (PhyGA in cm) + (PtGA in cm).
Time frame: Weeks 36 and 48
Double Blind Phase: Percentage of Participants With Remission Assessed by SDAI <=3.3 at Weeks 36 and 48
SDAI was calculated from tender and swollen joints using 28 joint count, PtGA, PhyGA and CRP (in mg/dL). PtGA and PhyGA both were assessed on 0-10 cm VAS scale (VAS: scores ranging from 0 cm \[very well\] to 10 cm \[worst\]), where higher scores indicated greater affliction due to disease activity). SDAI total score ranged from 0 to 86, where higher scores indicated higher disease activity. SDAI score of \<=11 indicates low disease activity and a score of \<=3.3 indicates remission. SDAI = (28TJC) + (28SJC) + (PhyGA in cm) + (PtGA in cm) + (CRP in mg/dL).
Time frame: Weeks 36 and 48
Double Blind Phase: Percentage of Participants Achieving an American College of Rheumatology 20 Percent (%) (ACR20) Response at Weeks 36 and 48
Participants with 20% improvement in tender and swollen joint counts and 20% improvement in at least 3 of the 5 measures: PtGA, PhyGA, participant's assessment of arthritis pain, Health Assessment Questionnaire-Disability Index (HAQ-DI) and CRP. PtGA: participant assessed health on VAS, 0 mm (very well) to 100 mm (worst health condition), higher scores = worse condition. PhyGA: physician judged participants' pain on VAS, 0 (no pain) to 100 mm (extreme pain), higher scores = more pain. Participant's assessment of arthritis pain: participant assessed pain on VAS, 0 mm (no pain) to 100 mm (most severe pain), higher score = more pain. HAQ-DI: functional disability evaluation, score: 0 (no difficulty) to 3 (extreme difficulty), higher score implied more disability. The improvement was relative to baseline (Day 1).
Time frame: Baseline (Day 1), Weeks 36 and 48
Double Blind Phase: Percentage of Participants Achieving an American College of Rheumatology 50% (ACR50) Response at Weeks 36 and 48
Participants with 50% improvement in tender and swollen joint counts and 50% improvement in at least 3 of the 5 measures: PtGA, PhyGA, participant's assessment of arthritis pain, HAQ-DI and CRP. PtGA: participant assessed health on VAS, 0 mm (very well) to 100 mm (worst health condition), higher scores = worse condition. PhyGA: physician judged participants' pain on VAS, 0 (no pain) to 100 mm (extreme pain), higher scores = more pain. Participant's assessment of arthritis pain: participant assessed pain on VAS, 0 mm (no pain) to 100 mm (most severe pain), higher score = more pain. HAQ-DI: functional disability evaluation, score: 0 (no difficulty) to 3 (extreme difficulty), higher score implied more disability. The improvement was relative to baseline (Day 1).
Time frame: Baseline (Day 1), Weeks 36 and 48
Double Blind Phase: Percentage of Participants Achieving an American College of Rheumatology 70% (ACR70) Response at Weeks 36 and 48
Participants with 70% improvement in tender and swollen joint counts and 70% improvement in at least 3 of the 5 measures: PtGA, PhyGA, participant's assessment of arthritis pain, HAQ-DI and CRP. PtGA: participant assessed health on VAS, 0 mm (very well) to 100 mm (worst health condition), higher scores = worse condition. PhyGA: physician judged participants' pain on VAS, 0 (no pain) to 100 mm (extreme pain), higher scores = more pain. Participant's assessment of arthritis pain: participant assessed pain on VAS, 0 mm (no pain) to 100 mm (most severe pain), higher score = more pain. HAQ-DI: functional disability evaluation, score: 0 (no difficulty) to 3 (extreme difficulty), higher score implied more disability. The improvement was relative to baseline (Day 1).
Time frame: Baseline (Day 1), Weeks 36 and 48
Double Blind Phase: Change From Randomization in Health Assessment Questionnaire-Disability Index (HAQ-DI) at Weeks 36 and 48
HAQ-DI assesses the degree of difficulty a participant has experienced during the past week in 8 domains of daily living activities: dressing/grooming; arising; eating; walking; reach; grip; hygiene; and other activities.. There were total of 30 items distributed in these 8 domains. Each item was scored on a 4-point scale from 0 to 3: 0= no difficulty; 1= some difficulty; 2= much difficulty; 3= unable to do. Overall score was computed as the sum of domain scores and divided by the number of domains answered. Total possible score range 0 (least difficulty) and 3 (extreme difficulty), where higher scores indicate more difficulty while performing daily living activities.
Time frame: Randomization (last non-missing measurement on or prior to the first dosing date in DB phase at Week 24), Weeks 36 and 48
Double Blind Phase: Change From Randomization in the Short Form 36 (SF-36) Health Survey 8 Domain Scores at Weeks 36 and 48
SF-36 is a participant reported standardized survey designed to assess generic health related quality of life. It consisted of 36 items evaluating 8 aspects of functional health and well-being: physical functioning, role physical, bodily pain, social functioning, mental health, role emotional, vitality, and general health perception. The score range for each of the 8 health aspects was from 0 (poor health) to 100 (better health), higher scores indicating good health condition. Scores of 8 health aspects were summarized to derive the 2 component scores (physical component scores \[PCS\], mental component scores \[MCS\]) ranging from 0 (worst) to 100 (best), where higher PCS/MCS indicated good health condition.
Time frame: Randomization (last non-missing measurement on or prior to the first dosing date in DB phase at Week 24), Weeks 36 and 48
Double Blind Phase: Change From Randomization in the SF-36 Health Survey Component Scores at Weeks 36 and 48
SF-36 is a participant reported standardized survey designed to assess generic health related quality of life. It consisted of 36 items evaluating 8 aspects of functional health and well-being: physical functioning, role physical, bodily pain, social functioning, mental health, role emotional, vitality, and general health perception. The score range for each of the 8 health aspects was from 0 (poor health) to 100 (better health), higher scores indicating good health condition. Scores of 8 health aspects were summarized aggregated to derive the two 2 component scores PCS and MCS ranging from 0 (worst) to 100 (best), where higher PCS/MCS indicated good health condition.
Time frame: Randomization (last non-missing measurement on or prior to the first dosing date in DB phase at Week 24), Weeks 36 and 48
Double Blind Phase: Change From Randomization in the Work Productivity and Activity Impairment (WPAI) Scores at Week 36 and 48
WPAI is 6-question participant rated questionnaire to determine the impact of rheumatoid arthritis and yields 4 types of outcomes: absenteeism (work time missed), presenteeism (impairment while working), work productivity loss (overall work impairment), and daily activity impairment (activity impairment) for a period of 7 days prior to a visit. These 4 outcomes are expressed as an impairment percentage (range from 0 to 100), with higher numbers indicating greater impairment and less productivity.
Time frame: Randomization (last non-missing measurement on or prior to the first dosing date in DB phase at Week 24), Week 36 and 48
Double Blind Phase: Change From Randomization in the European Quality of Life - 5 Dimensions Questionnaire (EQ-5D) Scores at Weeks 36 and 48
EQ-5D was a participant completed instrument designed to assess impact on quality of life in terms of a single utility score in 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression. 3 possible answers for mobility: 1=no problem in walking, 2=moderate problems in walking, 3= confined to bed; self-care: 1=no problem, 2=moderate problems, 3= unable to wash/dress; usual activities: 1=no problem, 2=moderate problems, 3= unable to do usual activities; pain and discomfort: 1=no pain or discomfort, 2=moderate pain or discomfort, 3= extreme pain or discomfort; anxiety and depression: 1=not anxious or depressed, 2=moderately anxious or depressed, 3= extremely anxious or depressed. The 5-dimensional systems are converted into a single index utility score between 0 and 1, where higher score indicated a better health state.
Time frame: Randomization (last non-missing measurement on or prior to the first dosing date in DB phase at Week 24), Weeks 36 and 48
Double Blind Phase: Change From Randomization in the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scale Scores at Weeks 36 and 48
The FACIT-Fatigue scale was a participant completed questionnaire consisted of 13 items that assessed fatigue. Each item was scored on a scale of 0 (maximum fatigue) to 4 (no fatigue), higher scores indicate less fatigue. Total FACIT-fatigue score was obtained by addition of scores from 13 items, giving a possible overall range from 0 (maximum fatigue) to 52 (no fatigue). Higher FACIT-fatigue scores indicated lower level of fatigue, better participant status.
Time frame: Randomization (last non-missing measurement on or prior to the first dosing date in DB phase at Week 24), Weeks 36 and 48
Double Blind Phase: Percentage of Participants Achieving an Improvement of at Least 0.22 Units in HAQ-DI at Weeks 36 and 48
HAQ-DI assesses the degree of difficulty a participant has experienced during the past week in 8 domains of daily living activities: dressing/grooming; arising; eating; walking; reach; grip; hygiene; and other activities.. There were total of 30 items distributed in these 8 domains. Each item was scored on a 4-point scale from 0 to 3: 0= no difficulty; 1= some difficulty; 2= much difficulty; 3= unable to do. Overall score was computed as the sum of domain scores and divided by the number of domains answered. Total possible score range 0 (least difficulty) and 3 (extreme difficulty), where higher scores indicate more difficulty while performing daily living activities. Percentage of participants with an improvement of at least 0.22 units in HAQ scores from baseline (Day 1) to Weeks 36 and 48 were reported in this outcome measure.
Time frame: Baseline (Day 1), Weeks 36 and 48
Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious AEs
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent were events between first dose of study drug and up to Week 52 (up to 28 days after last dose) that were absent before treatment or that worsened relative to pretreatment state. AEs included both serious and non-serious AEs.
Time frame: For OL Phase: Baseline up to Week 24; For DB Phase: Week 24 up to Week 52 (up to 28 days after last dose)
Number of Participants With Abnormal Laboratory Parameters
Abnormality criteria: Hemoglobin (Hb),Hematocrit,Erythrocytes(Ery): \<0.8\*LLN;Ery. Mean corpuscular volume \<0.9\*lower limit of normal (LLN), \>1.1\*upper limit of normal (ULN); Platelets:\<0.5\*LLN,\>1.75\*ULN;WBCs:\<0.6\*LLN,\>1.5\*ULN; Lymphocytes/WBCs, Neutrophils/WBCs:\<0.8\*LLN,\>1.2\* ULN;Basophils,Basophils/WBCs,Eosinophils,Eosinophils/WBCs,Monocytes, Monocytes/WBCs: \>1.2\*ULN;Prothrombin Time, Prothrombin Intl. Normalized Ratio:\>1.1\*ULN; ESR:\>1.5\*ULN; Bilirubin,Direct Bilirubin,Indirect Bilirubin: \>1.5\*ULN; Aspartate Aminotransferase (AT),Alanine AT,Gamma Glutamyl Transferase,Alkaline Phosphatase:\>3.0\*ULN; Protein, Albumin: \<0.8\*LLN, \>1.2x ULN; Blood Urea Nitrogen, Creatinine, Triglycerides: \>1.3\*ULN;HDL Cholesterol:\<0.8\*LLN;Sodium \<0.95\*LLN, \>1.05\*ULN;Potassium, Chloride, Calcium, Bicarbonate: \<0.9\*LLN, \>1.1\*ULN; Glucose: \<0.6\*LLN, \>1.5\*ULN; Creatine Kinase: \>2.0\*ULN; Cholesterol:\>1.3\*ULN;Specific Gravity:\<1.003;pH:\<4.5; urine glucose,Ketones,urine protein,urine Hb,WBCs Esterase: \>=1.
Time frame: For OL Phase: Baseline up to Week 24; For DB Phase: Week 24 up to Week 48
| Milestone | Open Label: Tofacitinib 11 mg + Methotrexate | Double Blind: Tofacitinib 11 mg + Methotrexate Placebo | Double Blind: Tofacitinib 11mg + Methotrexate |
|---|---|---|---|
| Started | 694 | 0 | 0 |
| Completed | 623 | 0 | 0 |
| Not completed | 71 | 0 | 0 |
| Withdrew: Adverse event | 39 | 0 | 0 |
| Withdrew: Lost to follow-up | 8 | 0 | 0 |
| Withdrew: Insufficient clinical response | 7 | 0 | 0 |
| Withdrew: Medication error,no linked adverse event | 2 | 0 | 0 |
| Withdrew: Protocol violation | 5 | 0 | 0 |
| Withdrew: Withdrawal by subject | 6 | 0 | 0 |
| Withdrew: Other | 4 | 0 | 0 |
| Milestone | Open Label: Tofacitinib 11 mg + Methotrexate | Double Blind: Tofacitinib 11 mg + Methotrexate Placebo | Double Blind: Tofacitinib 11mg + Methotrexate |
|---|---|---|---|
| Started | 0 | 267 | 266 |
| Treated | 0 | 264 | 266 |
| Completed | 0 | 238 | 247 |
| Not completed | 0 | 29 | 19 |
| Withdrew: Adverse event | 0 | 6 | 6 |
| Withdrew: Death | 0 | 0 | 2 |
| Withdrew: Lost to follow-up | 0 | 1 | 1 |
| Withdrew: Screen failure | 0 | 1 | 0 |
| Withdrew: Withdrawal by subject | 0 | 5 | 2 |
| Withdrew: Other | 0 | 2 | 5 |
| Withdrew: Insufficient clinical response | 0 | 6 | 1 |
| Withdrew: Protocol violation | 0 | 5 | 2 |
| Withdrew: Randomized but not treated | 0 | 3 | 0 |
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.
| units on a scale | Double Blind: Tofacitinib 11 mg + Methotrexate Placebo | Double Blind: Tofacitinib 11mg + Methotrexate |
|---|---|---|
| Double Blind Phase: Change From Randomization in Disease Activity Score in 28 Joints Using 4 Variables (DAS28-4) (Erythrocyte Sedimentation Rate [ESR]) at Week 48 | 0.33 ± 0.07 | 0.03 ± 0.07 |
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.
| units on a scale | Double Blind: Tofacitinib 11 mg + Methotrexate Placebo | Double Blind: Tofacitinib 11mg + Methotrexate |
|---|---|---|
| Double Blind Phase: Change From Randomization in DAS28-4 ESR at Week 36 | 0.40 ± 0.07 | 0.18 ± 0.07 |
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.
| units on a scale | Double Blind: Tofacitinib 11 mg + Methotrexate Placebo | Double Blind: Tofacitinib 11mg + Methotrexate |
|---|---|---|
| Change at Week 36 | 0.38 ± 0.06 | 0.13 ± 0.06 |
| Change at Week 48 | 0.29 ± 0.06 | 0.01 ± 0.06 |
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).
| units on a scale | Double Blind: Tofacitinib 11 mg + Methotrexate Placebo | Double Blind: Tofacitinib 11mg + Methotrexate |
|---|---|---|
| Change at Week 36 | 3.58 ± 0.49 | 1.84 ± 0.48 |
| Change at Week 48 | 2.97 ± 0.48 | 0.84 ± 0.47 |
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).
| units on a scale | Double Blind: Tofacitinib 11 mg + Methotrexate Placebo | Double Blind: Tofacitinib 11mg + Methotrexate |
|---|---|---|
| Change at Week 36 | 3.83 ± 0.52 | 1.88 ± 0.51 |
| Change at Week 48 | 3.16 ± 0.50 | 0.94 ± 0.49 |
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.
| percentage of participants | Double Blind: Tofacitinib 11 mg + Methotrexate Placebo | Double Blind: Tofacitinib 11mg + Methotrexate |
|---|---|---|
| Week 36 | 42.42 | 48.12 |
| Week 48 | 45.08 | 49.62 |
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.
| percentage of participants | Double Blind: Tofacitinib 11 mg + Methotrexate Placebo | Double Blind: Tofacitinib 11mg + Methotrexate |
|---|---|---|
| Week 36 | 65.53 | 70.68 |
| Week 48 | 65.91 | 74.44 |
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).
| percentage of participants | Double Blind: Tofacitinib 11 mg + Methotrexate Placebo | Double Blind: Tofacitinib 11mg + Methotrexate |
|---|---|---|
| Week 36 | 66.29 | 73.68 |
| Week 48 | 65.15 | 77.07 |
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).
| percentage of participants | Double Blind: Tofacitinib 11 mg + Methotrexate Placebo | Double Blind: Tofacitinib 11mg + Methotrexate |
|---|---|---|
| Week 36 | 66.29 | 73.31 |
| Week 48 | 66.29 | 76.32 |
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.
| percentage of participants | Double Blind: Tofacitinib 11 mg + Methotrexate Placebo | Double Blind: Tofacitinib 11mg + Methotrexate |
|---|---|---|
| Week 36 | 15.53 | 24.06 |
| Week 48 | 22.35 | 23.68 |
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.
| percentage of participants | Double Blind: Tofacitinib 11 mg + Methotrexate Placebo | Double Blind: Tofacitinib 11mg + Methotrexate |
|---|---|---|
| Week 36 | 20.45 | 28.57 |
| Week 48 | 23.86 | 30.08 |
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.
| percentage of participants | Double Blind: Tofacitinib 11 mg + Methotrexate Placebo | Double Blind: Tofacitinib 11mg + Methotrexate |
|---|---|---|
| Week 36 | 50.00 | 55.64 |
| Week 48 | 50.38 | 54.51 |
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).
| percentage of participants | Double Blind: Tofacitinib 11 mg + Methotrexate Placebo | Double Blind: Tofacitinib 11mg + Methotrexate |
|---|---|---|
| Week 36 | 23.48 | 32.33 |
| Week 48 | 28.41 | 30.83 |
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).
| percentage of participants | Double Blind: Tofacitinib 11 mg + Methotrexate Placebo | Double Blind: Tofacitinib 11mg + Methotrexate |
|---|---|---|
| Week 36 | 22.73 | 31.58 |
| Week 48 | 28.79 | 31.95 |
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).
| percentage of participants | Double Blind: Tofacitinib 11 mg + Methotrexate Placebo | Double Blind: Tofacitinib 11mg + Methotrexate |
|---|---|---|
| Week 36 | 73.86 | 80.83 |
| Week 48 | 73.11 | 79.70 |
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).
| percentage of participants | Double Blind: Tofacitinib 11 mg + Methotrexate Placebo | Double Blind: Tofacitinib 11mg + Methotrexate |
|---|---|---|
| Week 36 | 53.79 | 66.54 |
| Week 48 | 55.30 | 67.29 |
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).
| percentage of participants | Double Blind: Tofacitinib 11 mg + Methotrexate Placebo | Double Blind: Tofacitinib 11mg + Methotrexate |
|---|---|---|
| Week 36 | 35.61 | 40.98 |
| Week 48 | 37.88 | 42.86 |
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.
| units on a scale | Double Blind: Tofacitinib 11 mg + Methotrexate Placebo | Double Blind: Tofacitinib 11mg + Methotrexate |
|---|---|---|
| Change at Week 36 | 0.10 ± 0.03 | 0.01 ± 0.03 |
| Change at Week 48 | 0.01 ± 0.03 | 0.00 ± 0.03 |
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.
| units on a scale | Double Blind: Tofacitinib 11 mg + Methotrexate Placebo | Double Blind: Tofacitinib 11mg + Methotrexate |
|---|---|---|
| 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 |
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.
| units on a scale | Double Blind: Tofacitinib 11 mg + Methotrexate Placebo | Double Blind: Tofacitinib 11mg + Methotrexate |
|---|---|---|
| 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 |
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.
| percentage impairment | Double Blind: Tofacitinib 11 mg + Methotrexate Placebo | Double Blind: Tofacitinib 11mg + Methotrexate |
|---|---|---|
| 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 |
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.
| units on a scale | Double Blind: Tofacitinib 11 mg + Methotrexate Placebo | Double Blind: Tofacitinib 11mg + Methotrexate |
|---|---|---|
| Change at Week 36 | -0.05 ± 0.01 | -0.01 ± 0.01 |
| Change at Week 48 | -0.02 ± 0.01 | 0.00 ± 0.01 |
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.
| units on a scale | Double Blind: Tofacitinib 11 mg + Methotrexate Placebo | Double Blind: Tofacitinib 11mg + Methotrexate |
|---|---|---|
| Change at Week 36 | -0.99 ± 0.43 | -0.80 ± 0.43 |
| Change at Week 48 | -0.34 ± 0.46 | -0.52 ± 0.45 |
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.
| percentage of participants | Double Blind: Tofacitinib 11 mg + Methotrexate Placebo | Double Blind: Tofacitinib 11mg + Methotrexate |
|---|---|---|
| Week 36 | 67.05 | 77.07 |
| Week 48 | 68.56 | 75.19 |
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.
| Participants | Open Label: Tofacitinib 11 mg + Methotrexate | Double Blind: Tofacitinib 11 mg + Methotrexate Placebo | Double Blind: Tofacitinib 11mg + Methotrexate |
|---|---|---|---|
| AEs | 362 | 107 | 109 |
| SAEs | 20 | 10 | 5 |
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.
| Participants | Open Label: Tofacitinib 11 mg + Methotrexate | Double Blind: Tofacitinib 11 mg + Methotrexate Placebo | Double Blind: Tofacitinib 11mg + Methotrexate |
|---|---|---|---|
| Number of Participants With Abnormal Laboratory Parameters | 682 | 263 | 263 |
Collected over Baseline (Day 1) up to Week 52. Non-serious events are listed at a 2% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Open Label: Tofacitinib 11 mg + Methotrexate | 0/694 (0%) | 20/694 (2.9%) | 158/694 (22.8%) |
| Double Blind: Tofacitinib 11 mg + Methotrexate Placebo | 0/264 (0%) | 10/264 (3.8%) | 24/264 (9.1%) |
| Double Blind: Tofacitinib 11mg + Methotrexate | 2/266 (0.8%) | 5/266 (1.9%) | 31/266 (11.7%) |
| Event | Open Label: Tofacitinib 11 mg + Methotrexate | Double Blind: Tofacitinib 11 mg + Methotrexate Placebo | Double Blind: Tofacitinib 11mg + Methotrexate |
|---|---|---|---|
| Pulmonary embolismRespiratory, thoracic and mediastinal disorders | 0/694 | 1/264 | 2/266 |
| PneumoniaInfections and infestations | 3/694 | 1/264 | 0/266 |
| Umbilical herniaGastrointestinal disorders | 0/694 | 1/264 | 0/266 |
| OsteomyelitisInfections and infestations | 0/694 | 1/264 | 0/266 |
| Femur fractureInjury, poisoning and procedural complications | 1/694 | 1/264 | 0/266 |
| Spinal compression fractureInjury, poisoning and procedural complications | 0/694 | 1/264 | 0/266 |
| Mobility decreasedMusculoskeletal and connective tissue disorders | 0/694 | 1/264 | 0/266 |
| Adrenal adenomaNeoplasms benign, malignant and unspecified (incl cysts and polyps) | 0/694 | 1/264 | 0/266 |
| GlioblastomaNeoplasms benign, malignant and unspecified (incl cysts and polyps) | 0/694 | 1/264 | 0/266 |
| Nerve root compressionNervous system disorders | 0/694 | 1/264 | 0/266 |
| Event | Open Label: Tofacitinib 11 mg + Methotrexate | Double Blind: Tofacitinib 11 mg + Methotrexate Placebo | Double Blind: Tofacitinib 11mg + Methotrexate |
|---|---|---|---|
| NasopharyngitisInfections and infestations | 35/694 | 5/264 | 7/266 |
| Upper respiratory tract infectionInfections and infestations | 33/694 | 4/264 | 6/266 |
| Alanine aminotransferase increasedInvestigations | 16/694 | 5/264 | 10/266 |
| NauseaGastrointestinal disorders | 20/694 | 0/264 | 0/266 |
| Urinary tract infectionInfections and infestations | 19/694 | 0/264 | 0/266 |
| ArthralgiaMusculoskeletal and connective tissue disorders | 0/694 | 7/264 | 2/266 |
| BronchitisInfections and infestations | 0/694 | 3/264 | 7/266 |
| HeadacheNervous system disorders | 17/694 | 0/264 | 0/266 |
| HypertensionVascular disorders | 17/694 | 0/264 | 0/266 |
| DiarrhoeaGastrointestinal disorders | 16/694 | 0/264 | 0/266 |
Open-label phase safety analysis set (Safety-OL) included all participants who received at least 1 dose of Tofacitinib MR 11 mg plus Methotrexate during open-label phase.
| Age, Continuous(Years) | Open Label: Tofacitinib 11 mg + Methotrexate |
|---|---|
| Mean | 56.77 ± 11.83 |
| Sex: Female, Male(Participants) | Open Label: Tofacitinib 11 mg + Methotrexate |
|---|---|
| Female | 532 |
| Male | 162 |
| Ethnicity (NIH/OMB)(Participants) | Open Label: Tofacitinib 11 mg + Methotrexate |
|---|---|
| Hispanic or Latino | 59 |
| Not Hispanic or Latino | 635 |
| Unknown or Not Reported | 0 |
| Race/Ethnicity, Customized(Participants) | Open Label: Tofacitinib 11 mg + Methotrexate |
|---|---|
| Asian | 37 |
| Black or African American | 33 |
| White | 594 |
| Others | 30 |
Showing the first 100 of 136 sites across 16 countries.
Documents are hosted by the registry — open the source record to download them.
Plan to share: Yes — Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.
This study is completed, as verified in Nov 2019. You cannot join it, but the record below documents what was studied.
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