JAKs, IL-23s Top Rankings for Endoscopic Response Induction in Crohn’s Disease

A network meta-analysis comparing the efficacy of advanced therapies in inducing endoscopic response among patients with moderate to severely active Crohn's disease concluded that Janus kinase inhibitors (JAKs) and anti-interleukin-23/p19 (IL-23) agents were the most efficacious among non-tumor necrosis factor antagonists (anti-TNFs).

The investigators searched MEDLINE, Embase, and Cochrane CENTRAL databases from inception to August 2, 2023, phase II and III randomized controlled trials (RCTs) in adults (≥18 years) with moderate to severe Crohn's disease. Participants in these trials treated with anti-TNFs, etrolizumab, vedolizumab, IL-12/23p40, anti-IL-23p19, or JAK1 inhibitors, were compared with cohorts on placebo/active comparators for induction and/or maintenance of remission and reported endoscopic outcomes. The primary outcomes was endoscopic response after induction therapy and endoscopic remission after maintenance therapy.

“A total of 20 RCTs (19 placebo-controlled and 1 head-to-head trial; 5592 patients) were included out of which 12 RCTs reported endoscopic outcomes for the induction phase, 5 reported for the maintenance phase, and 3 reported for both induction and maintenance phases,” the researchers reported in Clinical Gastroenterology and Hepatology. “JAK1 inhibitors (RR, 3·49 [95% CI, 1·48-8·26]) and anti-IL23p19 (RR, 2·30 [95% CI, 1·02-5·18]) agents were more efficacious than etrolizumab (moderate certainty of evidence), and JAK1 inhibitors (RR, 2·34 [95% CI, 1·14-4·80]) were more efficacious than anti-IL12/23p40 agents for inducing endoscopic response (moderate certainty of evidence). JAK1 inhibitors and anti-IL23p19 ranked highest for induction of endoscopic response.”

The authors noted that they found “paucity of RCTs of TNF antagonists reporting endoscopic outcomes with induction therapy. On network meta-analysis of 6 RCTs, all agents except vedolizumab (RR, 1.89 [95% CI, 0.61-5.92]) were effective in maintaining endoscopic remission compared with placebo.”

Overall, the team concluded that JAK1 inhibitors, TNF antagonists, and IL12/23p40 agents ranked highest.

“Future head-to-head trials will further inform positioning of different therapies for the management of Crohn's disease,” they concluded.

Reference:

Vuyyuru SK, Nguyen TM, Murad MH, et al. Comparative efficacy of advanced therapies for achieving endoscopic outcomes in Crohn's disease: a systematic review and network meta-analysis. Clin Gastroenterol Hepatol. 2024;22(6):1190-1199.e15.  doi:10.1016/j.cgh.2023.12.023.