Re-establishment of efficacy of tofacitinib, an oral JAK inhibitor, after temporary discontinuation in patients with rheumatoid arthritis

INTRODUCTION/OBJECTIVE: Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). This post-hoc analysis evaluated the effect of temporary discontinuation and reinitiation of tofacitinib on disease control in patients with RA in the vaccine sub-study of the long-term extension (LTE) study ORAL Sequel (NCT00413699). METHODS: The sub-study of ORAL Sequel was a randomized, parallel-group, open-label study. Patients who received tofacitinib 10 mg twice daily for ≥ 3 months in ORAL Sequel were randomized to receive continuous (tofacitinib monotherapy/with methotrexate) or interrupted (tofacitinib withdrawn for 2 weeks post-randomization then reinitiated as monotherapy/with methotrexate) treatment. Efficacy assessments included ACR20/50/70 response rates, change from baseline (∆) in C-reactive protein (CRP), Health Assessment Questionnaire-Disability Index (HAQ-DI), Disease Activity Score in 28 joints, erythrocyte sedimentation rate (DAS28-4 [ESR]), Clinical Disease Activity Index (CDAI), Patient Global Assessment of arthritis (PtGA), Pain (Visual Analog Scale [VAS]), and Physician Global Assessment of arthritis (PGA). Safety was assessed throughout. RESULTS: The sub-study included 99 patients each in the continuous and interrupted treatment groups. ACR20/50 response rates, ∆CRP, ∆HAQ-DI (day 15), ∆DAS28-4 (ESR), ∆CDAI, ∆PtGA, ∆Pain (VAS), and ∆PGA were significantly worse in interrupted vs continuous patients during dose interruption, but were generally similar to pre-interruption/continuous treatment levels 28 days post-reinitiation. A numerically higher proportion of interrupted patients reported adverse events (49.5%) vs continuous patients (35.4%). CONCLUSIONS: Tofacitinib efficacy can be re-established after temporary withdrawal and reinitiation. The safety profile of patients who temporarily discontinued tofacitinib in the sub-study was consistent with previous tofacitinib LTE studies over 9 years. CLINICAL TRIAL REGISTRATION NUMBER: NCT00413699