P501 Effects of continued vedolizumab therapy for ulcerative colitis in week 6 induction therapy nonresponders

Abstract

Background: Vedolizumab (VDZ), a gut-selective, humanized, anti-α4β7 integrin monoclonal antibody, was evaluated for the treatment of ulcerative colitis (UC) in the 52-week GEMINI 1 trial. In this study, 47.1% of patients had a clinical response to VDZ induction therapy at week 6. Here the efficacy of continuing VDZ therapy is evaluated in week 6 nonresponders to VDZ induction therapy. Methods: GEMINI 1 participants were randomly assigned to receive placebo (PBO) or VDZ 300 mg (cohort 1) or assigned to receive open-label VDZ (cohort 2) intravenously at weeks 0 and 2. Patients who did not respond to VDZ induction therapy at week 6 received open-label VDZ every 4 weeks (Q4W) during maintenance, whereas all PBO patients continued on PBO. Clinical response (reduction in partial Mayo Clinic score [MCS] of ≥2 points and decrease of ≥25% from the baseline score, with an accompanying reduction in rectal bleeding subscore of ≥1 point or a rectal bleeding subscore of 0 or 1) and clinical remission (partial MCS of ≤2 points and no subscore >1 point) were assessed in week 6 nonresponders at weeks 10 and 14 (prespecified) and at week 52 (post hoc). Week 52 post hoc analyses were also performed for mucosal healing (Mayo Clinic scale endoscopic subscore of 0 or 1) in week 6 nonresponders and for efficacy end points in week 6 nonresponders who had clinical response at week 10 or 14. Results: At baseline, the median duration of UC in VDZ week 6 nonresponders (4.6 years) was comparable to week 6 responders. Baseline UC activity (ie, complete MCS) was higher in VDZ week 6 nonresponders (median, 9.0) than inweek 6 responders (median, 8.0), whichwas attributable mainly to a greater proportion of patients withMCS of 9 to 12 (56% of week 6 nonresponders, 42% of week 6 responders). Rate of previous tumor necrosis factor antagonist failure was higher among week 6 nonresponders (51%) than among week 6 responders (32%). Proportions of week 6 nonresponders who had clinical response, clinical remission, or mucosal healing at weeks 10, 14, and 52 were numerically greater with VDZ than with PBO (Table). These differences were most pronounced at week 52. For both VDZ and PBO, the proportions of week 6 nonresponders who had clinical response, clinical remission, or mucosal healing at week 52 were similar between those who responded at week 10 and those who responded at week 14; the small numbers of PBO-treated patients in these subgroups are a limitation of this analysis. Conclusions: Patients with UC who did not have a clinical response to VDZ induction therapy at week 6 and continued VDZ Q4W had higher rates of clinical response and remission at weeks 10, 14, and 52 and of mucosal healing at week 52 than did those who received PBO.