Efficacy Of Vedolizumab (Vdz) By Disease Extension In Ulcerative Colitis (Uc)

Disease extension in ulcerative colitis (UC) is one of the major factors determining long-term prognosis. Patients with extensive colitis have more frequent complications, extraintestinal manifestations and systemic symptoms, need more immunosuppressive and surgical therapies, and have a greater cancer risk. It is, therefore, important to determine whether the efficacy of available treatments is affected by disease extension. Results of the pivotal GEMINI 1 trial suggested that VDZ, a humanised monoclonal α4β7 antibody approved for UC, is efficacious regardless of disease extension. A post hoc analysis was conducted on the maintenance phase intent-to-treat (mITT) population of the GEMINI 1 trial to further examine VDZ efficacy by disease extension and any potential confounding factors. The following efficacy outcomes were assessed at Week 52 by disease extension (proctosigmoiditis, left-sided colitis, extensive colitis, pancolitis): clinical response (reduction in complete Mayo score ≥3 points and ≥30% reduction from baseline with a decrease in rectal bleeding subscore ≥1 point, or absolute rectal bleeding score of ≤1 point); clinical remission (Mayo score ≤2 points and no individual subscore >1); corticosteroid (CS)-free remission in patients receiving CSs at baseline; and mucosal healing (Mayo endoscopic subscore ≤1). Logistic regression assessed the impact of disease extension (extensive colitis vs. pancolitis, left-sided colitis vs. pancolitis, proctosigmoiditis vs. pancolitis), prior anti-TNFα therapy, prior CS exposure, concomitant immunomodulator use and baseline calprotectin on clinical response, clinical remission and mucosal healing at Week 52. The mITT population comprised 373 patients (proctosigmoiditis: 41; left-sided colitis: 149; extensive colitis: 45; pancolitis: 138). VDZ improved all four efficacy measures vs. placebo at both study dose regimens (every 4 weeks or every 8 weeks) across all disease extension subgroups. Efficacy outcomes by disease extension. None of the potential confounding factors included in the logistic regression analysis were found to be significant. VDZ (both dosing regimens) was more efficacious than placebo at improving disease activity in patients with UC. Disease extension, prior and/or concomitant therapy, and calprotectin levels did not impact this result. A limitation of this analysis was the small patient number in each subgroup; larger studies are required to identify any statistically significant differences.