Tofacitinib with methotrexate in third-line treatment of patients with active rheumatoid arthritis: patient-reported outcomes from a phase III trial

Abstract

Objective: To assess patient-reported outcomes (PROs) for tofacitinib, an oral JAK inhibitor for the treatment of rheumatoid arthritis (RA), in a 6-month, phase III, randomized controlled trial.

Methods: Patients ages ≥18 years with active RA with an inadequate response to ≥1 tumor necrosis factor inhibitor (TNFi) and receiving stable background methotrexate were randomized 2:2:1:1 to tofacitinib 5 mg or 10 mg twice daily, or placebo advanced to tofacitinib 5 mg or 10 mg twice daily at month 3. PROs measured at month 3 included patient global assessment of disease activity (PtGA), pain, Health Assessment Questionnaire (HAQ) disability index (DI), Medical Outcomes Study (MOS) Short Form 36 Health Survey version 2 (SF-36v2; acute), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), and MOS Sleep Scale.

Results: Patients received tofacitinib 5 mg (n = 133) or 10 mg (n = 134) or placebo advanced to tofacitinib 5 mg (n = 66) or 10 mg (n = 66). HAQ DI (reported previously), PtGA (P < 0.0001), and SF-36v2 physical and mental component summary (P < 0.05) scores were improved for both tofacitinib doses versus placebo. Furthermore, improvements greater than or equal to the minimum clinically important difference were more frequently reported by tofacitinib-treated patients versus placebo for PtGA (P < 0.05), pain (P < 0.0001), HAQ DI (P < 0.05), SF-36v2 physical and mental component summary scores (P < 0.05), and FACIT-F (P < 0.001 for 5 mg twice daily). No statistical differences were observed in the MOS Sleep Scale.

Conclusion: Tofacitinib treatment resulted in significant, clinically meaningful improvements in multiple PROs versus placebo over 3 months of treatment in patients with active RA and a previous inadequate response to TNFi.

Trial registration: ClinicalTrials.gov NCT00960440.