BACKGROUND: Decisions regarding the treatment of ulcerative colitis (UC) should be based on appropriate, high quality evidence. In the absence of head-to-head trials, network meta-analysis (NMA) can be used to compare the efficacy and safety of several treatments. We conducted an NMA to compare the efficacy of ontamalimab (anti-MAdCAM-1) using its phase 2 data, with all other biologics and novel small molecules for which induction study data on response and remission in patients with UC were available.
METHODS: A systematic literature review was conducted in November 2017 to identify published randomized controlled trials of induction treatment in patients with moderate-to-severe UC. An NMA of the identified studies was performed using random-effects models and methods based on NICE guidance. Odds ratios and 95% credible intervals were calculated to describe the relative differences between all treatments and placebo in terms of efficacy in inducing response and remission. Results were generated for anti-TNF-naïve and experienced populations.
RESULTS: A total of 14 phase 2 and phase 3 induction studies of the following agents were included: adalimumab (160/80mg), etrolizumab (100mg and300 mg), golimumab (200/100mg), infliximab (5mg), ontamalimab (22.5mg and 75mg), ozanimod (0.5mg and 1mg), tofacitinib (10mg) and vedolizumab (300mg). The definitions of response and remission used across trials were consistent. Between-study homogeneity was good and enabled pooling of results. Figure 1 shows odds ratios for induction of response and remission with treatments relative to placebo in anti-TNF-naïve and -experienced patients. All treatments, including ontamalimab, significantly differentiated from placebo in anti-TNF-naïve patients, with the exception of etrolizumab and ozanimod for response and remission, respectively. Tofacitinib (p=0.0043) and infliximab (p=0.0013) were superior to adalimumab in inducing response; whereas etrolizumab 100mg (p=0.0377), as well as tofacitinib (p=0.0287) and infliximab (p=0.0163), was superior to adalimumab in inducing remission.
CONCLUSIONS: This study suggests ontamalimab and most other treatments induce response and remission better than placebo. Although conducted before any large-scale head-to-head trials of these drugs, the study suggests a few treatments could be superior to adalimumab in terms of efficacy. However, varying endpoint timings, the combination of phase 2 and 3 data, and lack of control for placebo response could underscore large variances in the data and preclude firm conclusions being drawn.
