Abstract Background Although several advanced therapies (ATs) for luminal Crohn’s disease (CD) have been approved, their efficacy for perianal fistulizing Crohn’s (pCD) has not been comprehensively reviewed. Methods A literature search was conducted in MEDLINE, Embase, and Cochrane CENTRAL up to October 2, 2025. Placebo-controlled randomized controlled trials (RCTs) evaluating treatment efficacy in pCD were included. Outcomes of interest were fistula response and fistula remission during the induction and maintenance trials. Pooled relative risks (RRs) were calculated using a random-effects model. Results Fourteen studies were eligible; only 4 RCTs were specifically designed for pCD, while the remainder were post hoc analyses of luminal CD studies with moderate to serious risk of bias. In pooled analyses of induction trials (4-28 weeks), ATs were associated with significantly higher induction of fistula response (RR 1.65, 95% CI 1.22-2.22) and remission (RR 1.91, 95% CI 1.37-2.67) compared to placebo. Infliximab and upadacitinib demonstrated significantly greater fistula response and remission, while ustekinumab significantly increased rates of fistula remission. For the maintenance phase (22-52 weeks), ATs were associated with significantly higher maintenance of fistula response (RR 1.54, 95% CI 1.21-1.97) and remission (RR 2.08, 95% CI 1.49-2.90) compared to placebo. Infliximab showed significantly greater maintenance of fistula response and remission compared with placebo, while adalimumab was superior for fistula remission. Conclusion Findings from our meta-analysis indicate that infliximab is effective for pCD, with limited evidence of benefit with adalimumab, ustekinumab, and upadacitinib. Well-designed RCTs investigating newer advanced therapies are needed to better guide targeted treatment strategies for this patient population.
Yuan et al. (Sat,) studied this question.