ABSTRACT: 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Sequel were randomized to receive continuous (tofacitinib monotherapy/with methotrexate) or interrupted (tofacitinib withdrawn for 2 weeks post-randomization then reinitiated as monotherapy/with methotrexate) treatment.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 Key Points • In this sub-study of the long-term extension (LTE) study, ORAL Sequel, the efficacy of tofacitinib was re-established after temporary withdrawal (2 weeks) and reinitation of treatment in patients with RA. • Patients with RA who temporarily discontinued tofacitinib had similar safety events to those reported in previous LTE studies. • The results of this sub-study were consistent with a post-hoc analysis of pooled data from two LTE studies, ORAL Sequel and A3921041, which assessed the efficacy of tofacitinib following a treatment discontinuation period of 14-30 days.
