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The following is a summary of “Efficacy and Safety of Upadacitinib for Perianal Fistulizing Crohn’s Disease: A Post Hoc Analysis of 3 Phase 3 Trials,” published in the May 2025 issue of Clinical Gastroenterology and Hepatology by Colombel et al. 

Researchers conducted a retrospective study to evaluate upadacitinib outcomes in patients with fistulizing Crohn’s disease (CD) from phase 3 induction and maintenance trials.  

They randomized patients (2:1) to receive once daily (QD) upadacitinib 45 mg or placebo for 12 weeks. Clinical responders on upadacitinib 45 mg were rerandomized (1:1:1) to receive upadacitinib 15 mg, upadacitinib 30 mg, or placebo for 52 weeks and assessed the resolution of drainage, closure of external openings, clinical remission, endoscopic response, and safety in patients with fistulas (any and perianal).  

The results showed that of 1,021 patients in U-EXCEL and U-EXCEED, 143 (14.0%) had fistulas at baseline, with 66 draining; most (n = 128) had perianal fistulas (56 draining). A higher proportion of patients receiving upadacitinib achieved resolution of drainage of perianal fistulas at the end of induction (placebo: 5.6%, n/n = 1/18; upadacitinib 45 mg: 44.7%, n/n = 17/38; P= .003) and maintenance (placebo: 0%, n/n = 0/11; upadacitinib 15 mg: 28.6%, n/n = 4/14; P= .105; upadacitinib 30 mg: 23.1%, n/n = 3/13; P= .223). Upadacitinib also led to greater closure of perianal fistula external openings in induction (placebo: 4.8%, n/n = 2/42; upadacitinib 45 mg: 22.1%, n/n = 19/86; P= .013) and maintenance (placebo: 0%, n/n = 0/30; upadacitinib 15 mg: 18.8%, n/n = 6/32; P= .024; upadacitinib 30 mg: 16.0%, n/n = 4/25; P= .037).  

Investigators concluded that patients with fistulizing disease, mainly perianal, who were treated with upadacitinib experienced greater rates of drainage resolution, external opening closure, clinical remission, and endoscopic response compared to those who received a placebo. 

Source: cghjournal.org/article/S1542-3565(24)00860-7/fulltext