P475 Association between disease duration and degree of endoscopic improvement in patients with ulcerative colitis treated with tofacitinib

Abstract

Abstract Background Tofacitinib is an oral, small-molecule JAK inhibitor for the treatment of ulcerative colitis (UC). Efficacy and safety of tofacitinib in patients with UC were evaluated in two Phase 3 induction studies (OCTAVE Induction 1 and 2; NCT01465763, NCT01458951), a 52-week, Phase 3 maintenance study (OCTAVE Sustain, NCT01458574), and an ongoing, open-label, long-term extension study (NCT01470612) [1,2]. Here, we evaluate the association between disease duration and the likelihood of achieving an endoscopic subscore of either 0 or 1 in OCTAVE Induction 1 and 2 and OCTAVE Sustain. Methods The degree of mucosal healing (Mayo endoscopic subscore of 0 or 1) achieved at Week 8 of OCTAVE Induction 1 and 2 (tofacitinib 10 mg twice daily [BID] or placebo) and at Week 52 of OCTAVE Sustain (responders from OCTAVE Induction 1 and 2; tofacitinib 5 or 10 mg BID or placebo) was evaluated in relation to UC disease duration at OCTAVE Induction 1 and 2 baseline (ie prior to study treatment). The association between disease duration category (<3, 3–6 and >6 years) and endoscopic subscore (centrally read) was assessed using the Cochran–Mantel–Haenszel chi-square test. Patients who did not achieve mucosal healing (as observed) were excluded. Results A total of 303/1139 (26.6%) patients achieved mucosal healing at Week 8 of OCTAVE Induction 1 and 2, and 190/593 (32.0%) at Week 52 of OCTAVE Sustain. Of patients who achieved mucosal healing at Week 8 of OCTAVE Induction 1 and 2 (with tofacitinib or placebo), 89 (29.4%), 76 (25.1%) and 138 (45.5%) had baseline disease durations of <3 years, 3–6 years and >6 years, respectively. Overall (among patients who achieved mucosal healing, treated with tofacitinib or placebo), no statistically significant association between disease duration and endoscopic subscore was observed, either at Week 8 of OCTAVE Induction 1 and 2 or at Week 52 of OCTAVE Sustain (chi-squared p = 0.13 and p = 0.23, respectively). In both OCTAVE Induction 1 and 2 and OCTAVE sustain, a numerically higher proportion of patients with shorter disease duration (<3 years) had complete mucosal healing (endoscopic subscore of 0) with tofacitinib vs. patients with longer disease duration (tofacitinib 10 mg BID and/or tofacitinib all groups) (Table). Conclusion Among patients with endoscopic improvement after induction and maintenance therapy with tofacitinib, rates of complete mucosal healing were numerically higher among those with UC for <3 years before starting treatment than among those with a longer disease duration. These analyses are post hoc and limited by the small sample size. References