Exploration of Post-market Evidence of Effectiveness and Safety of TNF-alpha Inhibitors in Crohn’s and Colitis

Abstract

The objectives of this thesis were to synthesize existing RCT evidence and post-market observational evidence of TNF-α inhibitors in IBD. Two separate systematic reviews were performed: an overview of systematic reviews of RCTs, and a systematic review of post-market observational studies of TNF-α inhibitors in Crohn’s disease and ulcerative colitis. The overview of systematic reviews included 37 studies. RCT evidence demonstrated superiority of all agents to placebo in Crohn’s disease and ulcerative colitis, with no increased risk of malignancy or serious adverse events. Network meta-analyses have not shown superiority of any agent compared to another. The second systematic review included 255 studies. Included studies were deemed to be unamenable to pooling with substantial methodological and clinical diversity. Available evidence is insufficient to determine whether real-world effectiveness and safety is consistent with RCTs, but suggests no increased risk of malignancy and no difference in efficacy between adalimumab and infliximab.