Issue 12

Clinical Question

Does adalimumab (ADA) lead to uniform mucosal healing throughout the gastrointestinal tract in patients with Crohn’s disease (CD)?

Editor’s Bottom Line

The rate and extent of mucosal healing on ADA for CD varies among ileal and colonic segments. Thorough reassessment may be required after starting therapy.

Reference

Reinisch W, Colombel JF, D’Haens G, et al. Characterization of Mucosal Healing with Adalimumab Treatment in Patients with Moderately to Severely Active Crohn’s Disease: Results from the EXTEND Trial. J Crohns Colitis. 2017 April:11(4):425–34. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5881717/

Synopsis

This was a post-hoc analysis of 52-week data from the randomized, double-blinded EXTEND Trial of ADA. The study included patients with moderately-to-severely active CD who received an initial ADA induction (160 mg at baseline, 80 mg at week 2) and then randomized to 40 mg ADA maintenance treatment every other week until 52 weeks, or a placebo on the same schedule. Investigators performed endoscopies at baseline and weeks 12 and 52 and measured mucosal healing using the CD Endoscopic Index of Severity (CDEIS), the Simple Endoscopic Scope for CD (SES-CD) and the Colonic and Ileal Global Histologic Disease Activity Scores (CGHAS/IGHAS). Baseline endoscopic severity scores were similar in the ADA and placebo groups. Most patients had colonic (87.8%) and ileal (71.4%) disease, with involvement distributed evenly across ileocolonic segments.

Of the 49 patients included in this analysis (ADA, 28; Placebo, 21), 35% of those in the ADA maintenance group had deep ulcers persistent at 52 weeks, compared to 75% of placebo recipients (P not noted). At 52 weeks, 54.2% of ADA maintenance recipients had superficial ulcers, compared to 90% of placebo recipients. Among ADA maintenance recipients, CDEIS scores showed greater reductions in the amount of ulcerated surface area at 52 weeks in the rectum (mean: -88.3%), sigmoid/left colon (-82.8%), and transverse colon (-75.3%), and lesser reductions in the right colon (-50%) and ileum (-30.9%). SES-CD scores measuring ulcer size showed more pronounced reductions in the sigmoid/left colon, rectum, transverse colon and right colon, with less pronounced reductions in size in the ileum. Notably, patterns of mucosal healing among ADA maintenance recipients at week 52 were similar to their improvements at 12 weeks. Histological improvements at 52 weeks among ADA maintenance recipients were slightly greater in the colon than the ileum.

Details

Study Design: Post-hoc analysis of randomized controlled trial
Funding: AbbVie Inc.
Allocation: Randomized
Setting: Multicenter trial
Level of Evidence: 1b (Oxford Levels of Evidence)

The summary and conclusion in this issue of E-mentoring in IBD pertains to the manuscript(s) being reviewed, and should be considered in the context of what is already known surrounding the topic and incorporated into practice as deemed appropriate by the individual learner.