Background/Purpose: Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). We compared patient-reported outcomes (PROs) among patients receiving tofacitinib monotherapy, tofacitinib + methotrexate (MTX), and adalimumab (ADA) + MTX, in a head-to-head trial of patients with RA and inadequate responses to MTX (MTX-IR).

Methods: ORAL Strategy (NCT02187055) was a Phase 3b/4, 1-year, triple dummy, active randomized controlled trial (RCT). Patients were randomized 1:1:1 to receive tofacitinib 5 mg twice daily (BID; tofa mono), tofacitinib 5 mg BID + MTX (tofa+MTX) or subcutaneous ADA 40 mg every other week + MTX (ADA+MTX); MTX doses were
15–25 mg/wk. PROs (secondary endpoints in this RCT) assessed at Months (Mos) 6 and 12 included mean changes from baseline in: patient global assessment of disease activity (visual analog scale [VAS]); arthritis pain (VAS); Health Assessment Questionnaire‑Disability Index (HAQ-DI); Short Form-36 Health Survey; EuroQol 5-dimensions Questionnaire; Work Productivity and Activity Impairment Questionnaire; Functional Assessment of Chronic Illness Therapy-Fatigue; and the proportion of patients reporting improvements in HAQ-DI ≥minimum clinically important difference (MCID; -0.22). Nominal p values were calculated with no adjustment for multiple comparisons.

Results: Among 1146 patients treated (tofa mono: n=384; tofa+MTX: n=376; ADA+MTX: n=386), baseline demographics and disease characteristics were comparable. At Mos 6 and 12, improvements in all PROs were similar for tofa+MTX and ADA+MTX (there were essentially no differences based on nominal p values) and numerically greater than with tofacitinib monotherapy (Table). Mean changes from baseline in HAQ-DI scores were similar in each treatment group at Mos 6 and 12; similar proportions reported improvements ≥MCID.

Conclusion: MTX-IR patients with RA reported PRO improvements with all 3 treatment regimens that were clinically meaningful, comparable for tofacitinib + MTX and adalimumab + MTX, and numerically higher with combination therapy than with tofacitinib monotherapy. Nominal p values should be interpreted with caution as they were not controlled for Type 1 error.