Tofacitinib for Induction Therapy in Patients with Active Ulcerative Colitis in Two Phase 3 Clinical Trials: Results by Local and Central Endoscopic Assessments

Abstract

Introduction: Tofacitinib is an oral, small molecule JAK inhibitor that is being investigated for ulcerative colitis (UC). Two Phase 3 randomized placebo-controlled studies (OCTAVE Induction 1 and 2: NCT01465763, NCT01458951) demonstrated efficacy of tofacitinib 10 mg twice daily (BID) vs placebo as induction therapy for patients (pts) with moderately to severely active UC.1 Here, we describe clinical efficacy endpoints assessed by local endoscopy readings along with the previously reported results assessed by central readings. Methods: Pts in both studies were randomized (4:1) to receive tofacitinib 10 mg BID or placebo for up to 9 weeks (wks). Pts were ≥18 years old with moderately to severely active UC (baseline Mayo score ≥6, rectal bleeding subscore ≥1 and endoscopic subscore ≥2). Pt eligibility was assessed based on central endoscopic reading. Pts had previous failure or intolerance to treatment with ≥1 of corticosteroids, thiopurines, or tumor necrosis factor inhibitors. The following efficacy endpoints were assessed at Wk 8: remission (primary endpoint; Mayo score ≤2, no subscore >1 and rectal bleeding subscore of 0), mucosal healing (Mayo endoscopic subscore ≤1) and clinical response (decrease from baseline Mayo score of ≥3 points and ≥30%, plus decrease in rectal bleeding subscore ≥1 or absolute subscore ≤1). Clinical outcomes were measured using both local (ie site) and central endoscopic readings at baseline and Wk 8.Table 1: Summary of efficacy endpoints at Wk 8 determined by local and central readingResults: At Wk 8, significantly more pts receiving tofacitinib 10 mg BID achieved remission in both studies vs placebo as demonstrated by both central and local endoscopic readings (Table). Similar results were observed with mucosal healing and clinical response at Wk 8. The observed rates as well as the magnitude of treatment differences based on local endoscopic reading were generally higher than those assessed by central reading. There was good agreement between locally and centrally read endoscopic subscores (kappa = 0.63 (95% CI 0.58, 0.67) and 0.62 (95% CI 0.57, 0.67) in OCTAVE Induction 1 and 2, respectively). Conclusion: In pts with moderately to severely active UC, who were qualified for both studies on central reading, treatment effects observed with local endoscopic readings were similar or slightly higher, and consistent with central readings. Both methods demonstrated the significant effect of tofacitinib vs placebo for induction therapy. Funded by Pfizer Inc. 1. Sandborn WJ et al. J Crohns Colitis 2016;10(S1):S15.