Comparative efficacy of biologics in the treatment of moderately to severely active ulcerative colitis (UC)

Abstract

Background: This study aimed to assess the comparative efficacy and safety of biologics in adult patients with moderately to severely active UC, stratified by prior exposure to anti-TNF inhibitors.

Methods: MEDLINE, Embase, The Cochrane Library, and ClinicalTrials.gov were systematically searched using a predefined search strategy, without language restrictions, for studies of approved biologics for UC (adalimumab, golimumab, infliximab, vedolizumab) published before February 2014. Two reviewers independently assessed studies for inclusion using a 2-step process; data on study design, patient characteristics, and outcomes were extracted from 8 RCTs (GEMINI I, ULTRA-1, ULTRA-2, ACT-1, ACT-2, PURSUIT-SC, PURSUIT-M, Suzuki et al., 2014 [1]) that met the inclusion criteria and were suitable for network metaanalysis (NMA). The NMA was conducted for key endpoints at induction and maintenance, where data were available, in R and OpenBUGS using Bayesian fixed effects mixed treatment comparisons. Assumptions were made to account for differences in maintenance study design.

Results: Seven studies were included in the analysis of induction treatment for anti-TNF-naïve patients. All biologics were more effective than placebo in terms of response, remission, and mucosal healing, but rankograms suggested no significant differences between the included biologics. These results were consistent with recent reports [2]. Five studies were included in the analysis of maintenance treatment for anti-TNF-naïve patients. Vedolizumab every 8 weeks (Q8W) resulted in improved results versus comparators for all outcomes at week 52 and was associated with a significantly higher rate of durable clinical response than all comparators (Table 1). In patients who had previously received anti-TNFs, only vedolizumab and adalimumab could be compared. At induction, no significant differences in efficacy were observed between the 2 biologics. During maintenance treatment, vedolizumab resulted in improved rates of durable response and remission and significantly improved rates of mucosal healing compared with adalimumab (Table 1).

Conclusions: This study adds to the current understanding of the comparative efficacy and safety of biologic treatment for UC, encompassing outcomes and populations not included in previous studies. All biologic treatments are effective in the treatment of UC, with vedolizumab demonstrating benefits compared with all comparators irrespective of prior anti-TNF exposure in the maintenance setting.