Outcomes of Tofacitinib Dose Reduction in Patients with Ulcerative Colitis in Stable Remission from the Randomised RIVETING Trial

Abstract

Abstract Background and Aims Tofacitinib is an oral, small molecule Janus kinase inhibitor for the treatment of ulcerative colitis. We present primary completion analysis from RIVETING, an ongoing, double-blind, randomised, parallel-group trial evaluating efficacy and safety of tofacitinib dose reduction to 5 mg twice daily [BID] versus remaining on 10 mg BID in patients in stable remission on tofacitinib 10 mg BID maintenance therapy. Methods Patients had received tofacitinib 10 mg BID for ≥ 2 consecutive years and been in stable remission for ≥ 6 months before enrolment. The primary endpoint was modified Mayo score remission at Month 6. Safety was assessed up to February 20, 2020 [data cut-off]. Results In all, 140 patients were randomised [1:1] to tofacitinib 5 or 10 mg BID; 77.1% and 90.0% of patients in the 5 and 10 mg BID groups, respectively, were in modified Mayo score remission at Month 6 (adjusted difference 12.9%; 95% confidence interval [CI] 0.5–25.0). Smaller differences between treatment groups were seen in patients with baseline endoscopic subscore of 0 versus 1 [9.8%; –3.0–22.6, and 21.1%; –6.1–48.2, respectively], and in patients without versus with prior tumour necrosis factor inhibitor [TNFi] failure [9.5%; –6.6–25.6, and 17.4%; –1.6–36.3, respectively]. Adverse events [AE] and serious AE rates were similar across treatment groups; no deaths were reported. Conclusions Most patients in stable remission on 10 mg BID maintenance therapy maintained remission following dose de-escalation. For patients who dose de-escalated, those in deep endoscopic remission and those without prior TNFi failure were more likely to maintain remission. Efficacy data were limited to the first 6 months; a longer duration of follow-up during RIVETING will further characterise the impact of dose reduction on maintenance of remission. Safety findings were consistent with the established safety profile of tofacitinib.