An Indirect Comparisons Analysis of Biologic Medications in the Maintenance of Response and Remission in Crohn’s Disease

Abstract

Introduction: Five biologic medications are approved to treat Crohn’s disease (CD), 3 tumor necrosis factor inhibitors (infliximab, adalimumab, and certolizumab pegol) and 2 selective adhesion molecule (SAM) inhibitors (natalizumab and vedolizumab). The vast majority of evidence supporting their individual efficacies is based on randomized controlled trials (RCTs) with placebo as the comparator arm. We performed a network meta-analysis (NMA) to determine the comparative efficacy of these biologic medications in maintaining a clinical response (defined by a decrease in Crohn’s disease activity index by more than 70 points) and remission (defined by a decrease in Crohn’s disease activity index by more than 150 points) at weeks 20 and 24. Methods: Studies were extracted from a electronic literature search of PubMed, MEDLINE and EMBASE of all relevant RCT’s. Twelve RCT’s, including 3,519 patients, were identified. There were 2 outcomes of interest: efficacy in maintaining response and remission at 20 and 24 weeks. There were several outcomes of interest for safety, such as serious infections, abdominal abscess and death. For each outcome, a fixed-effects meta-analysis was used. A mixed-treatment comparisons analysis was then utilized 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: In terms of maintenance of response at 20 weeks, patients taking natalizumab had a 90% (RR 0.10; 95% confidence interval [CI] 0.02-0.59) reduced likelihood of maintaining response when compared to adalimumab. In terms of maintenance of remission at 20 weeks vedolizumab had a 66% reduced likelihood of maintenance of remission when compared to adalimumab (RR 0.34; 95% CI 0.13-0.70). Regarding maintenance of response and remission at 24 weeks, similar outcomes of superiority of adalimumab over certolizumab and vedolizumab were noted although not statistically significant. In terms of rank probability adalimumab had a 71% chance of being the option most likely to maintain response and 72% chance of maintaining remission at 24 weeks. No statistical significance was noted comparing one drug to another in terms of safety. The degree of incoherence was low for all outcomes. Conclusion: This NMA was the first comparison to include all approved biologic medications, including SAM inhibitors-natalizumab and vedolizumab to compare maintenance of response and remission with different efficacy outcomes. Based on the above statistical analysis, adalimumab may be considered a superior option to other biologic medications for maintaining response and remission at 20 weeks.