Symptomatic Improvement Within 3 Days With Tofacitinib Induction Therapy in Patients With Ulcerative Colitis: Results From OCTAVE Induction 1 and 2

Abstract

Introduction: Tofacitinib is an oral, small molecule JAK inhibitor that is being investigated for ulcerative colitis (UC). Two Phase (P) 3 UC induction trials demonstrated the efficacy of tofacitinib 10 mg twice daily (BID) at Week 2 in partial Mayo score (PMS).1 We evaluated the onset of symptomatic improvement in a post-hoc analysis of diary data. Methods: OCTAVE Induction 1 (NCT01465763) & 2 (NCT01458951) were identical, randomized, placebo-controlled P3 trials in adult patients (pts) with moderately to severely active UC who had failed or were intolerant to steroids, immunomodulators, or tumor necrosis factor inhibitors. Pts received placebo (N=234) or tofacitinib 10 mg BID (N=905) for 8 weeks. Pooled data for OCTAVE Induction 1 & 2 are presented. At screening, pts electronically recorded their normal number of stools per day. During the study, pts continued a daily diary recording their number of bowel movements per day and the presence and description of any blood in the stools. Daily Mayo stool frequency (SF) and rectal bleeding (RB) subscores were calculated for each pt (subscore range of 0-3) based on that day's diary data for the first 15 days of therapy. Least squares mean (LSM) changes from baseline in SF and RB subscores were compared using a linear mixed-effects model. Binary endpoints were compared using stratified Cochran-Mantel-Haenszel chi-square test based on observed data. Results: At baseline for both the placebo and tofacitinib groups, mean SF Mayo subscore was 2.5 and mean RB Mayo subscore was 1.6. Significant improvements from baseline were observed with tofacitinib vs placebo at Day 3 for SF and RB subscores, and were maintained through to Day 15 (Figure). At Day 15, LSM changes from baseline for SF and RB subscores with tofacitinib were -0.74 and -0.76, respectively, vs -0.35 and -0.44, respectively, with placebo (P < 0.0001). At Day 15, 14.6% of tofacitinib-treated pts had an SF score of 0 vs 8.0% with placebo (P < 0.01), and 41.2% of tofacitinib-treated pts had an RB subscore of 0 vs 21.1% with placebo (P < 0.0001).FigureConclusion: In these two P3 induction studies of tofacitinib for pts with moderately to severely active UC, significant symptomatic improvements were observed with tofacitinib vs placebo as early as Day 3. These results support rapid onset of tofacitinib efficacy previously reported based on improvement in PMS.1 Funded by Pfizer Inc.