Phase 4
Completed N=694
Methotrexate Withdrawal Study of Tofacitinib Modified Release Formulation in Subjects With Rheumatoid Arthritis
Source: ClinicalTrials.gov NCT02831855 ↗Enrolled (actual)
694
Serious AEs
2.9%
Results posted
Dec 2019
Primary outcomePrimary: 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; 0.03 units on a scale — p=0.0005
◆ Published Evidence
Highly cited
162citations · ~54 / year
Malignancy risk with tofacitinib versus TNF inhibitors in rheumatoid arthritis: results from the open-label, randomised controlled ORAL Surveillance trial.
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.
Linked Publications (5)
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Malignancy risk with tofacitinib versus TNF inhibitors in rheumatoid arthritis: results from the open-label, randomised controlled ORAL Surveillance trial.
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Identification of two tofacitinib subpopulations with different relative risk versus TNF inhibitors: an analysis of the open label, randomised controlled study ORAL Surveillance.
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Methotrexate withdrawal in patients with rheumatoid arthritis who achieve low disease activity with tofacitinib modified-release 11 mg once daily plus methotrexate (ORAL Shift): a randomised, phase 3b/4, non-inferiority trial.
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Fracture in clinical studies of tofacitinib in rheumatoid arthritis.
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Machine learning prediction and explanatory models of serious infections in patients with rheumatoid arthritis treated with tofacitinib.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Double Blind Phase: Change From Randomization in Disease Activity Score in 28 Joints Using 4 Variables (DAS28-4) (Erythrocyte Sedimentation Rate [ESR]) at Week 48 |
0.33; 0.03 | 0.0005 sig |
| SECONDARY Double Blind Phase: Change From Randomization in DAS28-4 ESR at Week 36 |
0.40; 0.18 | — |
| SECONDARY Double Blind Phase: Change From Randomization in DAS28-4 (C-reactive Protein [CRP]) at Weeks 36 and 48 |
0.38; 0.13; 0.29; 0.01 | — |
| SECONDARY Double Blind Phase: Change From Randomization in Clinical Disease Activity Index (CDAI) at Weeks 36 and 48 |
3.58; 1.84; 2.97; 0.84 | — |
| SECONDARY Double Blind Phase: Change From Randomization in Simplified Disease Activity Index (SDAI) at Weeks 36 and 48 |
3.83; 1.88; 3.16; 0.94 | — |
| SECONDARY Double Blind Phase: Percentage of Participants With Low Disease Activity (LDA) Assessed by DAS28-4 (ESR) Less Than or Equal to (<=) 3.2 at Weeks 36 and 48 |
42.42; 48.12; 45.08; 49.62 | — |
| SECONDARY Double Blind Phase: Percentage of Participants With LDA Assessed by DAS28-4 (CRP) <=3.2 at Weeks 36 and 48 |
65.53; 70.68; 65.91; 74.44 | — |
| SECONDARY Double Blind Phase: Percentage of Participants With LDA Assessed by CDAI <=10 at Weeks 36 and 48 |
66.29; 73.68; 65.15; 77.07 | — |
| SECONDARY Double Blind Phase: Percentage of Participants With LDA Assessed by SDAI <=11 at Weeks 36 and 48 |
66.29; 73.31; 66.29; 76.32 | — |
| SECONDARY Double Blind Phase: Percentage of Participants With Remission Assessed by American College of Rheumatology-European League Against Rheumatism (ACR-EULAR) Boolean at Weeks 36 and 48 |
15.53; 24.06; 22.35; 23.68 | — |
| SECONDARY Double Blind Phase: Percentage of Participants With Remission Assessed by DAS28-4 (ESR) Less Than [<] 2.6 at Weeks 36 and 48 |
20.45; 28.57; 23.86; 30.08 | — |
| SECONDARY Double Blind Phase: Percentage of Participants With Remission Assessed by DAS28-4 (CRP) <2.6 at Weeks 36 and 48 |
50.00; 55.64; 50.38; 54.51 | — |
| SECONDARY Double Blind Phase: Percentage of Participants With Remission Assessed by CDAI <=2.8 at Weeks 36 and 48 |
23.48; 32.33; 28.41; 30.83 | — |
| SECONDARY Double Blind Phase: Percentage of Participants With Remission Assessed by SDAI <=3.3 at Weeks 36 and 48 |
22.73; 31.58; 28.79; 31.95 | — |
| SECONDARY Double Blind Phase: Percentage of Participants Achieving an American College of Rheumatology 20 Percent (%) (ACR20) Response at Weeks 36 and 48 |
73.86; 80.83; 73.11; 79.70 | — |
| SECONDARY Double Blind Phase: Percentage of Participants Achieving an American College of Rheumatology 50% (ACR50) Response at Weeks 36 and 48 |
53.79; 66.54; 55.30; 67.29 | — |
| SECONDARY Double Blind Phase: Percentage of Participants Achieving an American College of Rheumatology 70% (ACR70) Response at Weeks 36 and 48 |
35.61; 40.98; 37.88; 42.86 | — |
| SECONDARY Double Blind Phase: Change From Randomization in Health Assessment Questionnaire-Disability Index (HAQ-DI) at Weeks 36 and 48 |
0.10; 0.01; 0.01; 0.00 | — |
| SECONDARY Double Blind Phase: Change From Randomization in the Short Form 36 (SF-36) Health Survey 8 Domain Scores at Weeks 36 and 48 |
-1.32; -0.88; -1.69; -0.02; -0.98; -0.84 | — |
| SECONDARY Double Blind Phase: Change From Randomization in the SF-36 Health Survey Component Scores at Weeks 36 and 48 |
-1.42; -0.60; -1.25; -0.43; -0.83; -0.92 | — |
| SECONDARY Double Blind Phase: Change From Randomization in the Work Productivity and Activity Impairment (WPAI) Scores at Week 36 and 48 |
-1.39; -3.00; 4.00; 0.81; 3.68; 0.67 | — |
| SECONDARY Double Blind Phase: Change From Randomization in the European Quality of Life - 5 Dimensions Questionnaire (EQ-5D) Scores at Weeks 36 and 48 |
-0.05; -0.01; -0.02; 0.00 | — |
| SECONDARY Double Blind Phase: Change From Randomization in the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scale Scores at Weeks 36 and 48 |
-0.99; -0.80; -0.34; -0.52 | — |
| SECONDARY Double Blind Phase: Percentage of Participants Achieving an Improvement of at Least 0.22 Units in HAQ-DI at Weeks 36 and 48 |
67.05; 77.07; 68.56; 75.19 | — |
Eligibility 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.
Data sourced from ClinicalTrials.gov (NCT02831855) and the linked publication. Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.