Tofacitinib for Maintenance Therapy in Patients With Active Ulcerative Colitis in the Phase 3 OCTAVE Sustain Trial: 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). A Phase 3, randomized, double-blind, placebo-controlled maintenance study (OCTAVE Sustain, NCT01458574) demonstrated the efficacy of tofacitinib 5 and 10 mg twice daily (BID) vs placebo (PBO) in patients (pts) with moderate to severe UC.1 Methods: We describe clinical efficacy endpoints assessed by local endoscopy readings and previously reported results assessed by central readings, to compare local vs central readings in the assessment of tofacitinib efficacy. Pts who completed OCTAVE Induction 1 (NCT01465763) or OCTAVE Induction 2 (NCT01458951) studies and achieved clinical response (decrease of baseline Mayo score ≥3 points and ≥30%, with decrease in rectal bleeding subscore ≥1 or absolute rectal bleeding subscore ≤1) were eligible to participate in OCTAVE Sustain. 593 pts were randomized (1:1:1) to PBO, tofacitinib 5 or 10 mg BID for 53 weeks (wks). Pts' eligibility was assessed based on central endoscopic reading. Pts were permitted concomitant treatment with oral corticosteroids; tapering was mandatory from baseline. Concomitant treatment with immunosuppressants and biologics was prohibited. Efficacy endpoints at Wk 52 included remission (primary endpoint: Mayo score ≤2, no subscore >1 and rectal bleeding subscore of 0), mucosal healing (Mayo endoscopic subscore ≤1) and clinical response. Results: At Wk 52, remission was achieved by significantly more pts with both tofacitinib doses vs PBO, as demonstrated by both central and local endoscopic readings, and similar results were observed with mucosal healing, clinical response and sustained steroid-free remission among pts in remission at baseline. Efficacy assessed by local endoscopic readings was numerically greater than central readings, except for clinical response. There was good agreement between locally and centrally read endoscopic subscores (kappa=0.6 [95% CI 0.5, 0.6]). Conclusion: Efficacy assessed by local endoscopic readings was numerically greater than efficacy assessed by central readings for tofacitinib 5 and 10 mg BID vs PBO. Overall, local endoscopic readings were consistent with central readings. Both methods demonstrated that both tofacitinib doses were more effective than PBO for maintenance therapy in pts with moderately to severely active UC. Funded by Pfizer Inc.Table: Table. Summary of efficacy endpoints at Wk 52, determined by local and central reading