Head-to-head comparison of biological drugs for inflammatory bowel disease: from randomized controlled trials to real-world experience

Abstract

During past years, the increasing knowledge of molecular mechanisms of inflammatory bowel disease (IBD) have led to the development of several targeted biological therapies. This great expansion of available medical options has prompted the need for comparative data between drugs. For years, given that most randomized controlled trials (RCTs) were performed only versus placebo, this demand has clashed with the absence of head-to-head trials comparing two or more treatments. The quality of evidence coming from real-world experience was low overall, so it was extremely difficult to clarify the correct positioning of the biologicals inside the therapeutic algorithms for IBD. Fortunately, times are changing: head-to-head comparative RCTs have been conducted or are ongoing, and the methodological quality of real-world studies is gradually increasing, mainly thanks to a higher rate of application of statistical methods capable of reducing the selection bias, such as the propensity score. In this evolving scenario, the increasing number of comparative RCTs is providing high-quality data for a correct drug positioning in IBD. In parallel, real-world observational studies are supporting the data coming from RCTs, and covering those comparisons not performed in the RCT setting. We believe that there is moderate evidence already available to support clinicians in the correct choice between different biologicals, and data will certainly be more robust in the near future.

A review of the therapeutic management of ulcerative colitis

“…Real-world studies are available; however, currently there is insufficient evidence available to determine superiority of one therapy over another. 115 …”

Real‐world effectiveness of vedolizumab compared to anti‐TNF agents in biologic‐naïve patients with ulcerative colitis: A two‐year propensity‐score‐adjusted analysis from the prospective, observational VEDOIBD‐study

“…Moreover, special patient groups, such as the elderly, patients with complications or extraintestinal manifestations, and patients with surgical resections, are often excluded from RCTs. Thus, in addition to RCTs, 14,15 more real‐world comparative studies 16,17 focusing, for example, on VEDO versus anti‐TNF therapies are needed 18 …”

“…Thus, in addition to RCTs, 14,15 more real-world comparative studies 16,17 focusing, for example, on VEDO versus anti-TNF therapies are needed. 18 The results of the VARSITY trial-the first head-to-head RCT comparing the efficacy of VEDO and ADA in patients with UCwere published in 2019. 10 These showed that the clinical remission rate for VEDO was superior to that for ADA after one year (31.3% vs. 22.5%, p = 0.006).…”

Effectiveness and Safety Profiles of Biological Therapies in Inflammatory Bowel Disease: Real Life Data from an Active Pharmacovigilance Project

“…The introduction of different treatment options makes it difficult to manage IBD patients, especially for the choice of the best biological therapy. In this context, real-world comparative data that analyzes the effectiveness of biologics could lead the physician to choose the most effective therapy in patients affected by IBD [ 14 ]. Nonetheless, the increased use of these drugs has been associated with the onset of some emerging safety issues, such as hypersensitivity and immunogenicity reactions, infections, vasculitis, and some types of malignancies, for which an adequate selection of patients eligible for treatment and post-marketing monitoring, especially in long-term use, is required [ 15 , 16 , 17 ].…”