Patient-reported outcomes for tofacitinib with and without methotrexate, or adalimumab with methotrexate, in rheumatoid arthritis: A phase IIIB/IV trial

© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. Objective To provide the first direct comparison of patient-reported outcomes (PROs) following treatment with tofacitinib monotherapy versus tofacitinib or adalimumab (ADA) in combination with methotrexate (MTX) in patients with rheumatoid arthritis (RA) with inadequate response to MTX (MTX-IR). Methods ORAL Strategy (NCT02187055), a phase IIIB/IV, head-to-head, randomised controlled trial, assessed non-inferiority between tofacitinib 5 mg two times per day monotherapy, tofacitinib 5 mg two times per day+MTX and ADA 40 mg every other week+MTX. PROs assessed included the following: Patient Global Assessment of disease activity (PtGA), Pain, Health Assessment Questionnaire-Disability Index, Functional Assessment of Chronic Illness Therapy-Fatigue and 36-Item Short-Form Health Survey (SF-36) summary and domain scores. Results Substantial improvements from baseline were reported across all PROs in all treatment arms, which, in the majority, met or exceeded minimum clinically important differences. Compared with tofacitinib monotherapy, tofacitinib+MTX combination treatment conferred significantly greater improvements in PtGA, Pain and SF-36 physical component summary scores at month 6. Statistically or numerically greater improvements were often, but not uniformly, reported for combination treatments compared with tofacitinib monotherapy at other time points. Conclusion Treatment with tofacitinib+MTX, ADA+MTX and tofacitinib monotherapy resulted in clinically meaningful improvements in PROs in MTX-IR patients with RA. These were comparatively greater with combination treatments versus tofacitinib monotherapy, although differences between treatment arms were small, limiting our ability to confer clinical meaning. Trial registration number NCT02187055

Tofacitinib versus methotrexate in rheumatoid arthritis

Background : Methotrexate is the most frequently used first-line antirheumatic drug. We report the findings of a phase 3 study of monotherapy with tofacitinib, an oral Janus kinase inhibitor, as compared with methotrexate monotherapy in patients with rheumatoid arthritis who had not previously received methotrexate or therapeutic doses of methotrexate. Methods : We randomly assigned 958 patients to receive 5 mg or 10 mg of tofacitinib twice daily or methotrexate at a dose that was incrementally increased to 20 mg per week over 8 weeks; 956 patients received a study drug. The coprimary end points at month 6 were the mean change from baseline in the van der Heijde modified total Sharp score (which ranges from 0 to 448, with higher scores indicating greater structural joint damage) and the proportion of patients with an American College of Rheumatology (ACR) 70 response (>= 70% reduction in the number of both tender and swollen joints and >= 70% improvement in three of five other criteria: the patient's assessment of pain, level of disability, C-reactive protein level or erythrocyte sedimentation rate, global assessment of disease by the patient, and global assessment of disease by the physician). Results : Mean changes in the modified total Sharp score from baseline to month 6 were significantly smaller in the tofacitinib groups than in the methotrexate group, but changes were modest in all three groups (0.2 points in the 5-mg tofacitinib group and <0.1 point in the 10-mg tofacitinib group, as compared with 0.8 points in the methotrexate group [ P<0.001 for both comparisons]). Among the patients receiving tofacitinib, 25.5% in the 5-mg group and 37.7% in the 10-mg group had an ACR 70 response at month 6, as compared with 12.0% of patients in the methotrexate group (P<0.001 for both comparisons). Herpes zoster developed in 31 of 770 patients who received tofacitinib (4.0%) and in 2 of 186 patients who received methotrexate (1.1%). Confirmed cases of cancer (including three cases of lymphoma) developed in 5 patients who received tofacitinib and in 1 patient who received methotrexate. Tofacitinib was associated with increases in creatinine levels and in low-density and high-density lipoprotein cholesterol levels. Conclusions : In patients who had not previously received methotrexate or therapeutic doses of methotrexate, tofacitinib monotherapy was superior to methotrexate in reducing signs and symptoms of rheumatoid arthritis and inhibiting the progression of structural joint damage. The benefits of tofacitinib need to be considered in the context of the risks of adverse events

ORAL SCAN: Effects Of The Oral JAK Inhibitor Tofacitinib In Combination With Methotrexate On Patient Reported Outcomes In a 24-Month Phase 3 Trial Of Active Rheumatoid Arthritis

Pathophysiology and treatment of rheumatic disease