Sa1795 An Indirect Comparisons Analysis of TNF Inhibitors vs. Selective Adhesion Molecule Inhibitors in the Induction of Response in Ulcerative Colitis

Abstract

Introduction: Five biologic medications have been proven to be efficacious to treat Ulcerative Colitis (UC), three tumor necrosis factor inhibitors (infliximab, adalimumab, and golimumab) and two Selective Adhesion Molecule (SAM) inhibitors (vedolizumab and etrolizumab). The vast majority of evidence supporting their individual efficacy is based on randomized controlled trials (RCTs) with placebo as the comparator arm. We performed a network metaanalysis (NMA) to determine the comparative efficacy of these biologic medications for the induction of clinical response in the treatment of ulcerative colitis Methods: Studies were extracted from an electronic literature search of PubMed, MEDLINE and EMBASE of all relevant RCTs. 9 RCTs, including 3,265 patients, were identified. The main outcome of interest for efficacy: induction of response, defined as a decrease from baseline in the total Mayo score by at least 3 points and a relative decrease by at least 30% with an accompanying decrease in the rectal bleeding subscore of at least 1 point or an absolute rectal bleeding subscore of 0 or 1. There were several outcomes of interest for safety, primarily serious infections, serious adverse events and adverse events causing discontinuation of the drug. For each outcome, a fixed-effects meta-analysis was employed to compare each drug to placebo. A mixed-treatment comparisons analysis was then used to compare each of these drugs to one another indirectly. Calculation of the probability that each treatment is best was implemented using the Bayesian Markov chain Monte Carlo method. Results: Patients taking Adalimumab had a 67% reduced likelihood of inducing response compared to Infliximab (RR 0.43 95% CI 0.27-0.72). In terms of rank probability, Infliximab had the highest probability of inducing response compared to Adalimumab and Vedolizumab. Overall, TNF inhibitors had a higher rank probability of inducing response compared to SAM inhibitors. In terms of adverse events, SAM inhibitors had a higher rank probability of causing adverse events when compared to TNF inhibitors. The degree of incoherence was low for all outcomes. Conclusion: This NMA to date is the first to compare the two groups of biologics, TNF inhibitors and SAM inhibitors including the new SAM inhibitoretrolizumab in the induction of response with different efficacy outcomes. The results of the study showed that TNF inhibitors seem to be more efficacious in inducing response in ulcerative colitis when compared to SAM inhibitors.