Tofacitinib as Induction and Maintenance Therapy in Japanese Patients with Active Ulcerative Colitis

Background: Tofacitinibis an oral, small molecule Janus kinase inhibitorapproved in Japan for the treatment of ulcerative colitis (UC). Differences in the safety profile of tofacitinibin Japanese patients versus the global population, such as a higher risk of herpes zoster, have been reported. Objectives: We conducted post hoc analyses of tofacitinibtreatment in Japanese patients with moderate-to-severe UC in two global phase III studies. Methods: In OCTAVEInduction 1 (NCT01465763), 62 patients were randomized to placebo or tofacitinib10 mg twice daily (b.i.d.). In OCTAVESustain (NCT01458574), 39 patients with clinical response in OCTAVEInduction 1 were re-randomized to placebo, tofacitinib5 mg, or 10 mg b.i.d. Efficacy endpoints included: remission (primary endpoint; total Mayo score ≤2; no individual subscore >1; rectal bleeding subscore 0); mucosal healing (Mayo endoscopic subscore ≤1); clinical response (≥30% and ≥3-point decrease from induction study baseline total Mayo score; decrease in rectal bleeding subscore ≥1 or absolute subscore ≤1). Adverse events (AEs) and clinical laboratory parameters were recorded. Results: At week 8 of OCTAVEInduction 1, 22.4% of patients achieved remission with tofacitinib(placebo, 7.7%). At week 52 of OCTAVESustain, 31.3% and 66.7% of patients receiving tofacitinib5 and 10 mg b.i.d., respectively, achieved remission (placebo, 9.1%). The occurrence of AEs or serious AEs in Japanese patients was generally similar to that in the global studypopulation, with no new or unexpected safety risks observed. Conclusions: Although patient numbers were small, tofacitinibdemonstrated numerically greater efficacy versus placebo among Japanese patients in OCTAVEInduction 1 and OCTAVESustain, with a safety profile consistent with that of the global studypopulation.