Tofacitinib for induction therapy in patients with active ulcerative colitis in two phase 3 clinical trials: results by local and central endoscopic assessments

Introduction: Tofacitinib is an oral, small molecule JAK inhibitor that is being investigated for ulcerative colitis (UC). Two Phase 3 randomised placebo‐controlled studies (OCTAVE Induction 1, NCT01465763; OCTAVE Induction 2, NCT01458951) demonstrated efficacy of tofacitinib 10 mg twice daily (BID) vs placebo as induction therapy for patients with moderately to severely active UC.1. Aims & Methods: We describe here the clinical efficacy endpoints assessed by local endoscopy readings along with the previously reported results assessed by central readings. Patients in OCTAVE Induction 1 and 2 were randomised (4:1) to receive treatment with tofacitinib 10 mg BID or placebo for up to 9 weeks (wks). Patients were ≥18 years old with moderately to severely active UC (baseline Mayo score ≥6, rectal bleeding subscore ≥1 and endoscopic subscore ≥2). Patient eligibility was assessed based on central endoscopic reading. Patients had previous failure or intolerance to treatment with ≥1 of corticosteroids, thiopurines, or tumour necrosis factor inhibitors. The following efficacy endpoints were assessed at Wk 8: mucosal healing (defined as Mayo endoscopic subscore ≥1), remission (study primary endpoint, defined as Mayo score ≤2, no subscore 41 and rectal bleeding subscore of 0) 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. Results: At Wk 8, significantly more patients receiving tofacitinib 10mg BID achieved mucosal healing in both studies vs placebo as demonstrated by both central and local endoscopic readings (Table). Similar results were observed with remission 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 patients with moderately to severely active UC, who were qualified for both Phase 3 studies on central reading, treatment effects observed with local endoscopic readings were similar or slightly higher and, overall, consistent with central readings. Both methods demonstrated the significant effect of tofacitinib vs placebo for induction therapy.