P305 Indirect comparison of two novel biologics for the treatment of Crohn's disease : network-meta analysis of ustekinumab vs vedolizumab

Abstract

Background: Long-term remission is an important treatment goal for patients with Crohn's disease (CD). While anti-TNF inhibitors are effective at inducing and maintaining remission in patients with moderate to severe CD, a considerable proportion of patients do not respond or lose response to these therapies over time. Therapies with new MOAs are emerging to address this unmet need but clinical trials often do not include direct comparison of these agents. Better understanding of relative clinical efficacy and safety is needed to determine optimal positioning of biologic therapies in the treatment algorithm. The aim of this analysis was to conduct an indirect comparison of efficacy of two novel MOA biologics: vedolizumab (VDZ), an anti-alpha4beta7 integrin, and ustekinumab (UST), an antibody directed against the p40 subunit of IL-12 and IL-23, as therapy for patients with moderately to severely active CD. Method(s): Induction and maintenance data from Phase 3, randomized, double-blind, placebo-controlled studies were used in the analysis: GEMINI II [1] for VDZ and UNIT-1, UNIT-2, and IM-UNITI [2] for UST. Bayesian Network Meta Analysis comparing VDZ and UST was performed with OpenBUGS v3.2.2. A binomial likelihood and a logit link function in a fixed effect model were used to account for variability in the placebo (PLA) effect across trials. Week 6 induction data were extracted for PLA, VDZ 300mg, UST 6mg/kg. Week 52 maintenance data were extracted for PLA, VDZ 300mg Q8W and Q4W, UST 90mg Q12W and Q8W. Results were stratified by prior exposure to anti-TNFs (induction: non-anti-TNF refractory, anti-TNF refractory; maintenance: anti-TNF naive, anti-TNF refrac-tory). Clinical remission was defined as CDAI