Issue 17

Clinical Question

For patients with moderate–severe Crohn’s disease (CD) treated with adalimumab (ADA), does mucosal healing occur evenly throughout the ileum and colon?

Editor’s Bottom Line

The rectum and left colon are the segments most sensitive to ADA with respect to mucosal healing.

Reference

Reinisch W, Colombel JF, D’Haens G, et al. Characterisation 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;11(4):425–34. https://www.ncbi.nlm.nih.gov/pubmed/27815351

Synopsis

In the parent study, EXTEND,* patients (CD Activity Index [CDAI]=220–450 with mucosal ulceration) received ADA induction therapy and at 4 weeks were randomized to ADA maintenance therapy or placebo (PBO) until week 52. Patients could switch to open-label ADA after week 8 for flares or non-response. Each patient had 3 or 4 endoscopies performed at: screening, week 12, at time of switch to open-label ADA, and week 52. Scoring (CD Endoscopic Index of Severity [CDEIS], Simple Endoscopic Score for CD [SES-CD]) was done for each of five ileocolonic segments and read centrally by one person blinded to patient treatment. Histology was scored (Colonic and Ileal Global Histologic Disease Activity Scores [CGHAS/IGHAS]) by one person also blinded.

A total of 49 patients were included with the following induction/maintenance therapy: ADA/ADA (n=28) and ADA/PBO (n=21). There were no significant differences at baseline for CD-related history, medications, or endoscopy or histology scores. In fact, no significant changes in mucosal healing were noted until week 52. Continued ADA was associated with significant improvements from baseline to week 52 when compared to placebo for CDEIS surface involvement and ulceration in the rectum and left colon (P≤0.041 for each) but non-significant improvements in the transverse colon, right colon, or the ileum. Results using SES-CD scores were similar. Patients with baseline CGHAS or IGHAS scores of ≥3 had marked improvements at week 52 in the colon (CGHAS, P=0.012) and ileum (IGHAS, P=0.027).

* Rutgeerts P, Van Assche G, Sandborn WJ, Wolf DC, Geboes K, Colombel JF, Reinisch W; EXTEND Investigators, Kumar A, Lazar A, Camez A, Lomax KG, Pollack PF, D’Haens G. Adalimumab induces and maintains mucosal healing in patients with Crohn’s disease: data from the EXTEND trial. Gastroenterology. 2012;142(5):1102–11. https://www.ncbi.nlm.nih.gov/pubmed/22326435

Details

Study Design: Post-hoc analysis of the parent study: the EXTEND RCT
Funding: AbbVie Inc.
Allocation: Patients were stratified by clinical response to ADA then randomized
Setting: 19 sites in Europe and North America
Level of Evidence: 2b (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.