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

<jats:title>Abstract</jats:title><jats:sec> <jats:title>Introduction/objective</jats:title> <jats:p>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).</jats:p> </jats:sec><jats:sec> <jats:title>Methods</jats:title> <jats:p>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Sequel were randomized to receive continuous (tofacitinib monotherapy/with methotrexate) or interrupted (tofacitinib withdrawn for 2 weeks post-randomization then reinitiated as monotherapy/with methotrexate) treatment.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.</jats:p> </jats:sec><jats:sec> <jats:title>Results</jats:title> <jats:p>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%).</jats:p> </jats:sec><jats:sec> <jats:title>Conclusions</jats:title> <jats:p>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.</jats:p> </jats:sec><jats:sec> <jats:title>Clinical trial registration number</jats:title> <jats:p><jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="https://clinicaltrials.gov/ct2/show/NCT00413699">NCT00413699</jats:ext-link><jats:table-wrap><jats:table><jats:tbody> <jats:tr> <jats:td colspan="2"><jats:bold>Key Points</jats:bold>• <jats:italic>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.</jats:italic>• <jats:italic>Patients with RA who temporarily discontinued tofacitinib had similar safety events to those reported in previous LTE studies.</jats:italic>• <jats:italic>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.</jats:italic></jats:td> </jats:tr> </jats:tbody></jats:table></jats:table-wrap></jats:p> </jats:sec>