Novel Therapies and Mucosal Healing in Crohn’s Disease

Risankizumab and other IL-23p19 inhibitors, along with the JAK-1 inhibitor upadacitinib, “seem to be effective in inducing mucosal healing and endoscopic response, particularly in patients who have failed previous therapies,” for moderate-to-severe Crohn’s disease (CD), wrote researchers in Expert Opinion on Therapeutic Targets.

The study specifically targeted pathways such as interleukin (IL)-12/23, IL-23, alpha 4 beta 7 integrins Janus kinase 1 (JAK1), and sphingosine-1-phosphate receptor (S1PR). “The rationale for selecting these specific pathways is their central role in modulating key inflammatory processes implicated in CD pathogenesis,” the investigators wrote. They compared these therapies with placebo for induction and maintenance of CD remission.

Noting that antitumor necrosis factor inhibitors (TNFi) remain “a cornerstone in the treatment of CD,” the investigators found that risankizumab and other IL-23p19 inhibitors “seem to be effective in inducing mucosal healing and endoscopic response, particularly in patients who have failed previous therapies,” the authors wrote. The anti-integrin vedolizumab has also shown effectiveness in mucosal healing, particularly among patients who were unexposed to TNFis, they noted.

The JAK-1 specific inhibitor upadacitinib has also demonstrated efficacy in achieving both clinical and endoscopic remission in CD, they added.

“These are promising advanced therapies for inducing endoscopic remission and mucosal healing,” the authors concluded. “Further research on novel biologics and small molecules should assess their long-term real-world effectiveness across broader patient populations.”

Reference:

Centanni L, Bencardino S, D'Amico F, et al. Targeting mucosal healing in Crohn's disease: efficacy of novel pathways and therapeutic targets. Expert Opin Ther Targets. 2024;28(11):963-978. DOI: 10.1080/14728222.2024.2433124