Methotrexate Withdrawal Study of Tofacitinib Modified Release Formulation in Subjects With Rheumatoid Arthritis

• ClinicalTrials.gov Identifier: NCT02831855
• Recruitment Status: Completed
• First Posted: July 13, 2016
• Results First Posted: December 4, 2019
• Last Update Posted: December 4, 2019
• Sponsor: Pfizer
• Information provided by (Responsible Party): Pfizer

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
Rheumatoid Arthritis	Drug: CP-690,550; Drug: Methotrexate; Drug: Placebo	Phase 4

Study Design

• Study Type: Interventional (Clinical Trial)
• 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: September 1, 2016
• Actual Primary Completion Date: November 19, 2018
• Actual Study Completion Date: December 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 Name: tofacitinib; 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 :

1. 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 [ Time Frame: 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 :

1. Double Blind Phase: Change From Randomization in DAS28-4 ESR at Week 36 [ Time Frame: 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.
2. Double Blind Phase: Change From Randomization in DAS28-4 (C-reactive Protein [CRP]) at Weeks 36 and 48 [ 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 ]
   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.
3. Double Blind Phase: Change From Randomization in Clinical Disease Activity Index (CDAI) at Weeks 36 and 48 [ 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 ]
   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).
4. Double Blind Phase: Change From Randomization in Simplified Disease Activity Index (SDAI) at Weeks 36 and 48 [ 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 ]
   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).
5. 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 [ Time Frame: 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.
6. Double Blind Phase: Percentage of Participants With LDA Assessed by DAS28-4 (CRP) <=3.2 at Weeks 36 and 48 [ Time Frame: 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.
7. Double Blind Phase: Percentage of Participants With LDA Assessed by CDAI <=10 at Weeks 36 and 48 [ Time Frame: 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).
8. Double Blind Phase: Percentage of Participants With LDA Assessed by SDAI <=11 at Weeks 36 and 48 [ Time Frame: 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).
9. 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 [ Time Frame: 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.
10. Double Blind Phase: Percentage of Participants With Remission Assessed by DAS28-4 (ESR) Less Than [<] 2.6 at Weeks 36 and 48 [ Time Frame: 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.
11. Double Blind Phase: Percentage of Participants With Remission Assessed by DAS28-4 (CRP) <2.6 at Weeks 36 and 48 [ Time Frame: 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.
12. Double Blind Phase: Percentage of Participants With Remission Assessed by CDAI <=2.8 at Weeks 36 and 48 [ Time Frame: 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).
13. Double Blind Phase: Percentage of Participants With Remission Assessed by SDAI <=3.3 at Weeks 36 and 48 [ Time Frame: 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).
14. Double Blind Phase: Percentage of Participants Achieving an American College of Rheumatology 20 Percent (%) (ACR20) Response at Weeks 36 and 48 [ Time Frame: 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).
15. Double Blind Phase: Percentage of Participants Achieving an American College of Rheumatology 50% (ACR50) Response at Weeks 36 and 48 [ Time Frame: 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).
16. Double Blind Phase: Percentage of Participants Achieving an American College of Rheumatology 70% (ACR70) Response at Weeks 36 and 48 [ Time Frame: 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).
17. Double Blind Phase: Change From Randomization in Health Assessment Questionnaire-Disability Index (HAQ-DI) at Weeks 36 and 48 [ 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 ]
    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.
18. Double Blind Phase: Change From Randomization in the Short Form 36 (SF-36) Health Survey 8 Domain Scores at Weeks 36 and 48 [ 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 ]
    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.
19. Double Blind Phase: Change From Randomization in the SF-36 Health Survey Component Scores at Weeks 36 and 48 [ 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 ]
    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.
20. Double Blind Phase: Change From Randomization in the Work Productivity and Activity Impairment (WPAI) Scores at Week 36 and 48 [ 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 ]
    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.
21. Double Blind Phase: Change From Randomization in the European Quality of Life - 5 Dimensions Questionnaire (EQ-5D) Scores at Weeks 36 and 48 [ 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 ]
    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.
22. Double Blind Phase: Change From Randomization in the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scale Scores at Weeks 36 and 48 [ 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 ]
    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.
23. Double Blind Phase: Percentage of Participants Achieving an Improvement of at Least 0.22 Units in HAQ-DI at Weeks 36 and 48 [ Time Frame: 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:

1. Number of Participants With Treatment Emergent Adverse Events (AEs) and 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) ]
   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.
2. Number of Participants With Abnormal Laboratory Parameters [ Time Frame: 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

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Key Inclusion Criteria

- Must be 18 years of age or older.

Have a score of 6 or greater on the 2010 American College of Rheumatology/European League Against Rheumatism Classification Criteria for Rheumatoid Arthritis at and/or prior to Screening Visit.

• Have ≥4 tender/painful joints on motion and ≥4 swollen joints (28 joint counts) at both Screening Visit and Baseline Visit (Visit 1).
• Have moderate to severe disease activity as defined by CDAI>10 and DAS28-4(ESR) ≥3.2 at Baseline Visit.
• Have taken an oral MTX treatment regimen (15-25mg/week) continuously for at least 4 months prior to the screening visit and has taken a stable weekly dose of oral MTX with supplemental folic acid or folinic acid for at least 4 weeks prior to the baseline visit (conversion from parenteral MTX to oral MTX will require stabilization of the treatment regimen for at least 1 month).
• Subjects must screen negative for active tuberculosis or inadequately treated tuberculosis infection (active or latent).

Key Exclusion Criteria

• Pregnant female subjects; breastfeeding female subjects; male subjects with partners currently pregnant; male subjects able to father children and female subjects of childbearing potential who are unwilling or unable to use 2 highly effective methods of contraception as outlined in this protocol for the duration of the study and for at least 3 months after the last dose of investigational product.
• Subjects with infection or infection history; subjects with any current malignancy or a history of malignancy (except adequately treated or excised non-metastatic basal cell or squamous cell cancer of the skin or cervical carcinoma in situ); subjects with history of, or current evidence for, severe gastrointestinal narrowing (pathologic or iatrogenic); and subjects with history of documented diverticulitis.
• Subjects with a history of insufficient response to ≥2 biologics, regardless of the class.

Contacts and Locations

Locations

United States, Alabama

Rheumatology Associates of North Alabama, PC

Huntsville, Alabama, United States, 35801-4418

United States, Arizona

Arthrocare, Arthritiscare & Research, PC

Gilbert, Arizona, United States, 85234

SunValley Arthritis Center, Ltd.

Peoria, Arizona, United States, 85381

United States, Arkansas

CHI St. Vincent Medical Group Hot Springs

Hot Springs, Arkansas, United States, 71913

United States, California

Med Investigations, Inc

Fair Oaks, California, United States, 95628

HCP Clinical Research, LLC

Huntington Beach, California, United States, 92646

Sierra Rheumatology

Roseville, California, United States, 95661

Pacific Arthritis Center Medical Group

Santa Maria, California, United States, 93454

Robin K. Dore, MD, Inc.

Tustin, California, United States, 92780

Inland Rheumatology and Osteoporosis Medical Group

Upland, California, United States, 91786

Inland Rheumatology Clinical Trials, Inc.

Upland, California, United States, 91786

Desert Valley Medical Group

Victorville, California, United States, 92395

United States, Florida

AARDS Research Inc

Aventura, Florida, United States, 33180

RASF-Clinical Research Inc

Boca Raton, Florida, United States, 33486

Omega Research Consultants

DeBary, Florida, United States, 32713

University of Florida College of Medicine - Jacksonville - Rheumatology Research

Jacksonville, Florida, United States, 32207

University of Florida, Rheumatology at ACC

Jacksonville, Florida, United States, 32209

Center for Arthritis and Rheumatic Diseases

Miami, Florida, United States, 33173

Jeffrey Alper, MD

Naples, Florida, United States, 34102

Medallion Clinical Research Institute, LLC

Naples, Florida, United States, 34102

Suncoast Clinical Research, Inc.

New Port Richey, Florida, United States, 34652

Florida Arthritis & Osteoporosis Center

Port Richey, Florida, United States, 34668

Gulf Coast Medical Center

Port Richey, Florida, United States, 34668

West Broward Rheumatology Associates, Inc.

Tamarac, Florida, United States, 33321

USF Health Morsani Center for Advanced Healthcare

Tampa, Florida, United States, 33612

BayCare Medical Group, Inc

Tampa, Florida, United States, 33614

United States, Idaho

Institute of Arthritis Research

Idaho Falls, Idaho, United States, 83404

United States, Illinois

Quincy Medical Group

Quincy, Illinois, United States, 62301

United States, Indiana

Beacon Medical Group Rheumatology Main Street

Granger, Indiana, United States, 46530

Diagnostic Rheumatology and Research, PC

Indianapolis, Indiana, United States, 46227

United States, Louisiana

Ochsner Clinic Baton Rouge

Baton Rouge, Louisiana, United States, 70836

United States, Massachusetts

Phase III Clinical Research

Fall River, Massachusetts, United States, 02720

Clinical Pharmacology Study Group

Worcester, Massachusetts, United States, 01605

United States, Michigan

Bronson Internal Medicine and Rheumatology

Battle Creek, Michigan, United States, 49015

Western Michigan University Homer Stryker MD

Kalamazoo, Michigan, United States, 49007

United States, Mississippi

North Mississippi Medical Clinics, Inc. - Clinical Research

Tupelo, Mississippi, United States, 38801

United States, New Jersey

Arthritis & Osteoporosis Associates

Freehold, New Jersey, United States, 07728

Radnet

Marlton, New Jersey, United States, 08053

Arthritis, Rheumatic & Back Disease Associates, P.A.

Voorhees, New Jersey, United States, 08043

Open MRI & Diagnostic Imaging of Wall

Wall, New Jersey, United States, 07719

United States, New York

AAIR Research Center

Rochester, New York, United States, 14618

United States, North Carolina

Physicians East, PA

Greenville, North Carolina, United States, 27834

PMG Research of Salisbury

Salisbury, North Carolina, United States, 28144

United States, North Dakota

Trinity Health Center-Medical Arts

Minot, North Dakota, United States, 58701

United States, Ohio

Group Health Associates

Cincinnati, Ohio, United States, 45236

Cincinnati Rheumatic Disease Study Group, Inc.

Cincinnati, Ohio, United States, 45242

STAT Research, Inc.

Dayton, Ohio, United States, 45417

United States, Oklahoma

Health Research of Oklahoma

Oklahoma City, Oklahoma, United States, 73103

Oklahoma Medical Research Foundation (OMRF)

Oklahoma City, Oklahoma, United States, 73104

Lynn Health Science Institute

Oklahoma City, Oklahoma, United States, 73112

United States, Pennsylvania

East Penn Rheumatology Associates, P.C.

Bethlehem, Pennsylvania, United States, 18015

Altoona Center for Clinical Research

Duncansville, Pennsylvania, United States, 16635

United States, South Carolina

Piedmont Arthritis Clinic

Greenville, South Carolina, United States, 29601

Articularis Healthcare Group dba ACME Research

Orangeburg, South Carolina, United States, 29118

Articularis Healthcare Group d/b/a Low Country Rheumatology

Summerville, South Carolina, United States, 29486

United States, Texas

Pioneer Research Solutions, Inc.

Cypress, Texas, United States, 77429

Metroplex Clinical Research Center

Dallas, Texas, United States, 75231

United States, Virginia

Center for Arthritis and Rheumatic Diseases

Chesapeake, Virginia, United States, 23320

Center for Arthritis and Rheumatic Diseases

Suffolk, Virginia, United States, 23435

Australia, New South Wales

Genesis Research Services Pty Ltd

Broadmeadow, New South Wales, Australia, 2292

Optimus Clinical Research Pty Ltd

Kogarah, New South Wales, Australia, 2217

Australia, Queensland

Rheumatology Research Unit

Maroochydore, Queensland, Australia, 4558

Australia, Victoria

Emeritus Research

Melbourne, Victoria, Australia, 3124

Belgium

ReumaClinic

Genk, Belgium, 3600

AZ Delta

Roeselare, Belgium, 8800

Bulgaria

University Multiprofile Hospital for Active Treatment Dr. G. Stranski EAD

Pleven, Bulgaria, 5800

Multiprofile Hospital for Active Treatment - Plovdiv AD, Rheumatology Department

Plovdiv, Bulgaria, 4000

Multiprofile Hospital for Active Treatment Trimontium OOD

Plovdiv, Bulgaria, 4000

University Multiprofile Hospital for Active Treatment - Kaspela EOOD

Plovdiv, Bulgaria, 4001

National Multiprofile Transport Hospital Tsar Boris III

Sofia, Bulgaria, 1233

Medical Centre Synexus Sofia EOOD

Sofia, Bulgaria, 1784

Czechia

CCBR Czech Brno, s.r.o.

Brno, Czech Republic, Czechia, 602 00

LEKARNA LANCIER s.r.o.

Brno, Czechia, 602 00

Lekarna Na Lidicke

Brno, Czechia, 602 00

Revmacentrum MUDr. Mostera, s.r.o., Revmatologie a interna

Brno, Czechia, 615 00

CCBR Ostrava, s.r.o.

Ostrava, Czechia, 702 00

Lekarna Rezidence Nova Karolina

Ostrava, Czechia, 702 00

Revmatologicky ustav, Lekrna

Praha 2, Czechia, 128 50

Revmatologicky ustav

Praha 2, Czechia, 128 50

Lekarna Hradebni s.r.o.

Uherske Hradiste, Czechia, 686 01

MEDICAL PLUS, s.r.o. Revmatologicka a osteologicka ambulance

Uherske Hradiste, Czechia, 686 01

PV - MEDICAL s.r.o., Revmatologicka ambulance

Zlin, Czechia, 760 01

Revmavita s.r.o, Lekarna

Zlin, Czechia, 760 01

Germany

Hamburger Rheuma Forschungszentrum I

Hamburg, Germany, 22391

Hungary

DRC Gyogyszervizsgalo Kozpont Kft.

Balatonfured, Hungary, 8230

Revita Rendelo

Budapest, Hungary, 1027

Qualiclinic Kft.

Budapest, Hungary, 1036

CRU Hungary Kft.

Miskolc, Hungary, 3529

Korea, Republic of

Clinical Trial Pharmacy, KyungHee University Hospital

Seoul, Korea, Republic of, 02447

KyungHee University Hospital

Seoul, Korea, Republic of, 02447

CTC Pharmacy, Seoul National University Hospital

Seoul, Korea, Republic of, 03080

Seoul National University Hospital

Seoul, Korea, Republic of, 03080

Konkuk University Medical Center

Seoul, Korea, Republic of, 05030

Clinical Trial Pharmacy, The Catholic University of Korea, Seoul St. Mary's Hospital

Seoul, Korea, Republic of, 06591

The Catholic University of Korea Seoul, St. Mary's Hospital

Seoul, Korea, Republic of, 06591

Mexico

Centro de Investigacion y Tratamiento Reumatologico SC Consultorio Medico de Reumatologia (CINTRE)

Mexico, Ciudad DE Mexico, Mexico, 11850

Morales Vargas Centro de Investigacion SC (Consultorio Anexo)

Leon, Guanajuato, Mexico, 37000

Philippines

Mary Mediatrix Medical Center

Lipa City, Batangas, Philippines, 4217

Far Eastern University - Nicanor Reyes Medical Foundation, Marian Medical Arts Bldg

Quezon City, Metro Manila, Philippines, 1118

Poland

Zdrowie OSTEO-MEDIC s.c. L i A. Racewicz, A i J. Supronik

Bialystok, Poland, 15-351

ClinicMed Daniluk, Nowak. Sp. j.

Bialystok, Poland, 15-879

Nzoz Bif - Med

Bytom, Poland, 41-902

Centrum Medyczne Pratia Krakow

Krakow, Poland, 30-002

Malopolskie Centrum Medyczne S.C.

Krakow, Poland, 30-510

NZOZ Lecznica MAK-MED. S.C.

Nadarzyn, Poland, 05-830

MTZ Clinical Research Sp. z o.o.

Warszawa, Poland, 02-106

Russian Federation

Federal State Budgetary Scientific Institution "Research Institute of Rheumatology

Moscow, Russian Federation, 115522

FSBEI HE "Orenburg State Medical University" of MoH RF

Orenburg, Russian Federation, 460000

FSBEI HE "Orenburg State Medical University" of MoH RF

Orenburg, Russian Federation, 460018

SPb SBIH "Consultative-Diagnostic Centre #85"

Saint Petersburg, Russian Federation, 198260

FSBIH "Clinical Hospital #122 n.a. L.G. Sokolov" of FMBA of Russia

Saint-Petersburg, Russian Federation, 194291

SBIH "Samara Regional Clinical Hospital n.a. V.D. Seredavin"

Samara, Russian Federation, 443095

NSHI "Departmental Hospital at Smolensk station OJSC "Russian Railways"

Smolensk, Russian Federation, 214025

SAHI YR Clinical Hospital of Emergency Medical Care n.a. N.V. Soloviev

Yaroslavl, Russian Federation, 150003

State Budgetary Institution of Healthcare of Yaroslavl Region "Regional Clinical Hospital"

Yaroslavl, Russian Federation, 150062

Slovakia

AAGS s.r.o.

Dunajska Streda, Slovakia, 929 01

MEDMAN s.r.o.

Martin, Slovakia, 03601

REUMACENTRUM s.r.o.

Partizanske, Slovakia, 958 01

MUDr. Zuzana Cizmarikova, s.r.o.

Poprad, Slovakia, 05801

Reumex s.r.o

Rimavska Sobota, Slovakia, 979 01

South Africa

St. Augustine's Hospital

Durban, Kwazulu Natal, South Africa, 4001

Spain

Complejo Hospitalario Universitario de Santiago

Santiago de Compostela, A Coruna, Spain, 15706

Hospital Universitario de Cruces

Baracaldo, Vizcaya, Spain, 48903

Hospital Infanta Luisa

Sevilla, Spain, 41010

United Kingdom

Countess of Chester Hospital NHS Foundation Trust

Chester, Cheshire, United Kingdom, CH2 1UL

Pharmacy (dispensary)

Chester, Cheshire, United Kingdom, CH2 1UL

Countess of Chester Hospital NHS Foundation Trust

Ellesmere Port, Cheshire, United Kingdom, CH65 6SG

Hampshire Hospitals NHS Foundation Trust

Basingstoke, Hampshire, United Kingdom, RG24 9NA

Pharmacy, Hampshire Hospitals NHS Foundation Trust

Basingstoke, Hampshire, United Kingdom, RG24 9NA

Department of Rheumatology, Wirral University Teaching Hospital NHS Foundation Trust

Wirral, Merseyside, United Kingdom, CH49 5PE

Pharmacy Department, Wirral University Teaching Hospital NHS Foundation Trust

Wirral, Merseyside, United Kingdom, CH49 5PE

Wirral University Teaching Hospital NHS Foundation Trust

Wirral, Merseyside, United Kingdom, CH49 5PE

Pharmacy Department

Dudley, WEST Midlands, United Kingdom, DY1 2HQ

The Dudley Group NHS Foundation Trust

Dudley, WEST Midlands, United Kingdom, DY1 2HQ

Pharmacy

Manchester, United Kingdom, M23 9LT

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)

Documents provided by Pfizer:

Study Protocol  [PDF] December 4, 2017

Statistical Analysis Plan  [PDF] November 9, 2018

More Information

Additional Information:

To obtain contact information for a study center near you, click here. 

Publications:

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.

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. doi: 10.4049/jimmunol.178.5.2623.

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. doi: 10.1016/j.molimm.2006.11.025. Epub 2007 Jan 17.

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.

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.

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.

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. No abstract available.

van Vollenhoven RF, Fleischmann R, Cohen S, Lee EB, Garcia 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.

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, Landewe 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.

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. No abstract available.

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.

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. doi: 10.1093/rheumatology/36.5.551.

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. doi: 10.2165/00019053-199304050-00006.

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. doi: 10.1002/cncr.10245.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Cohen SB, Haraoui B, Curtis JR, Smith TW, Woolcott J, Gruben D, Murray CW. Impact of Methotrexate Discontinuation, Interruption, or Persistence in US Patients with Rheumatoid Arthritis Initiating Tofacitinib + Oral Methotrexate Combination. Clin Ther. 2022 Jul;44(7):982-997.e2. doi: 10.1016/j.clinthera.2022.05.002. Epub 2022 Jun 4.

Cohen SB, Pope J, Haraoui B, Mysler E, Diehl A, Lukic T, Liu S, Stockert L, Germino R, Menon S, Shi H, Keystone EC. Efficacy and safety of tofacitinib modified-release 11 mg once daily plus methotrexate in adult patients with rheumatoid arthritis: 24-week open-label phase results from a phase 3b/4 methotrexate withdrawal non-inferiority study (ORAL Shift). RMD Open. 2021 Jun;7(2):e001673. doi: 10.1136/rmdopen-2021-001673.

• Responsible Party: Pfizer
• ClinicalTrials.gov Identifier: NCT02831855
• Other Study ID Numbers: A3921192; 2016-001825-15 ( EudraCT Number )
• First Posted: July 13, 2016
• Results First Posted: December 4, 2019
• Last Update Posted: December 4, 2019
• Last Verified: November 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: 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.
• URL: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests

Keywords provided by Pfizer:

Rheumatoid Arthritis; Tofacitinib; CP-690,550; Xeljanz; methotrexate withdrawal; withdrawal study

Additional relevant MeSH terms:

Arthritis; Arthritis, Rheumatoid; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Methotrexate; Tofacitinib; Abortifacient Agents, Nonsteroidal; Abortifacient Agents; Reproductive Control Agents; Physiological Effects of Drugs; Antimetabolites, Antineoplastic; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Dermatologic Agents; Enzyme Inhibitors; Folic Acid Antagonists; Immunosuppressive Agents; Immunologic Factors; Antirheumatic Agents; Nucleic Acid Synthesis Inhibitors; Janus Kinase Inhibitors; Protein Kinase Inhibitors