Anti-TNFs versus vedolizumab and ustekinumab in Crohn’s disease

A post-hoc analysis of pivotal clinical trials showed that the TNF inhibitors adalimumab and infliximab generally outperformed vedolizumab and ustekinumab with regard to endoscopic healing of the ileum and colon in participants with Crohn’s disease (CD). However, in biologic-naïve participants, TNFs and ustekinumab did not display significant differences for endoscopic healing of the colon.

Recent evidence has demonstrated that large ulcers of the ileum and rectum are less likely to heal with infliximab compared with other biologic therapies. In addition, no trials have been conducted to compare biologic therapies for ileal and colonic healing in patients with CD.

Dr Neeraj Narula (McMaster University, Canada) and colleagues performed a pooled analysis that included 344 participants with CD who were enrolled in clinical trials [1]. All participants had received continuous adalimumab, infliximab, ustekinumab, or vedolizumab. The primary endpoint was 1-year endoscopic healing, defined as a simple endoscopic score for Crohn's disease (SES-CD) of 0. Results were adjusted for potential confounders including disease duration, concomitant corticosteroid use, and prior anti-TNF failure.

In participants with ileal involvement, vedolizumab showed the lowest proportion of patients achieving one-year endoscopic healing (18.6%), whereas infliximab was associated with the highest proportion compared with vedolizumab (36.7%; P=0.038). In addition, adalimumab (30%; P=0.225) and ustekinumab (22.7%; P=0.694) demonstrated numerically higher rates of segment endoscopic healing than vedolizumab but were not significant. Similar results were obtained in participants who displayed ileal ulcers >5 mm. Notably, there was no significant difference between biologic therapies for endoscopic healing in biologic-naïve participants with ileal involvement: adalimumab (37.5%) versus vedolizumab (21.9%; P=0.200); infliximab (36.7%) versus vedolizumab (P=0.130); ustekinumab (40.0%) versus vedolizumab (P=0.255).

Among participants with colonic disease, ustekinumab showed the lowest rate of colonic endoscopic healing (29.0%). Adalimumab (62.5%; P<0.001) and infliximab (52.4%; P=0.041) demonstrated significantly higher rates of colonic endoscopic healing compared with ustekinumab. Vedolizumab was associated with an endoscopic healing rate of 31.3% and did not differ from ustekinumab (P=0.987). In participants with colonic ulcers >5 mm, infliximab and adalimumab had the highest colonic endoscopic healing rates, whereas ustekinumab had the lowest endoscopic healing rate. These results were similar in biologic-naïve participants.

“Despite that these results were confirmed in multivariate analysis, our study cannot compete with a true head-to-head study,” admitted Dr Narula. “Moreover, the rapidity of onset of the compared biologics may partially explain the results we have observed. Certain biologic treatments need to be continued for a longer time before endoscopic healing occurs. Nonetheless, TNF inhibitors were in general superior to vedolizumab and ustekinumab for reaching endoscopic healing of the ileum and colon in these participants.”

1. Narula N, et al. Comparative Efficacy of Biologics for Endoscopic Healing of the Ileum and Colon in Crohn’s Disease. OP10, ECCO 2022, 16–19 February.

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Posted on 12 April 20228 April 2024