Tofacitinib in Combination With Conventional Disease-Modifying Antirheumatic Drugs in Patients With Active Rheumatoid Arthritis: Patient-Reported Outcomes From a Phase III Randomized Controlled Trial

Abstract

Objective: Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). We compared patient-reported outcomes (PROs) in patients with RA treated with tofacitinib or placebo in combination with conventional disease-modifying antirheumatic drugs (DMARDs).

Methods: In a 12-month, phase III randomized controlled trial (ORAL Sync), patients (n = 795) with active RA and previous inadequate response to therapy with ≥1 conventional or biologic DMARD were randomized 4:4:1:1 to tofacitinib 5 mg twice daily (BID), tofacitinib 10 mg BID, placebo advanced to 5 mg BID, or placebo to 10 mg BID, in combination with stable background DMARD therapy. PROs included patient global assessment of arthritis (PtGA), patient assessment of arthritis pain (Pain), physical function (Health Assessment Questionnaire disability index [HAQ DI]), health-related quality of life (Short Form 36 health survey [SF-36]), fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue [FACIT-F]), and sleep (Medical Outcomes Study Sleep [MOS Sleep]).

Results: At month 3, statistically significant improvements from baseline versus placebo were reported in PtGA, Pain, HAQ DI, all 8 SF-36 domains, FACIT-F, and MOS Sleep with tofacitinib 10 mg BID, and in PtGA, Pain, HAQ DI, 7 SF-36 domains, FACIT-F, and MOS Sleep with tofacitinib 5 mg BID. Improvements were sustained to month 12. Significantly more tofacitinib-treated patients reported improvements of greater than or equal to the minimum clinically important differences at month 3 versus placebo in all PROs, except the SF-36 role-emotional domain (significant for tofacitinib 10 mg BID).

Conclusion: Patients with active RA treated with tofacitinib combined with background conventional DMARD therapy reported sustained, significant, and clinically meaningful improvements in PROs versus placebo.

Trial registration: ClinicalTrials.gov NCT00856544.

Figure 1

Least squares mean (LSM) change from baseline over time for: A, patient global assessment of arthritis (PtGA), B, patient assessment of arthritis pain (Pain), C, Short Form 36 health survey (SF‐36) physical component summary (PCS) score, and D, SF‐36 mental component summary (MCS) score (full analysis set, no imputation). Horizontal dotted lines represent the minimum clinically important differences (MCIDs). Arrow and vertical dotted line denote completion of advancement to tofacitinib for patients randomized to placebo. Advancement to tofacitinib was at month 3 for placebo nonresponders and at month 6 for all remaining placebo‐treated patients. BID = twice daily; * = P < 0.05; ** = P < 0.01; *** = P < 0.0001 versus placebo.

Figure 2

Spydergram representing mean overall Short Form 36 health survey domain scores at month 3 (full analysis set, no imputation). Baseline values (orange) were pooled (with weighting) across all 3 treatment groups. BID = twice daily.