Introduction
Perianal fistulizing Crohn's disease (pCD) affects 20–30% of patients and represents one of the most challenging manifestations of inflammatory bowel disease, associated with severe impairment in health-related quality of life, recurrent septic complications, and high surgical morbidity. Anti-tumor necrosis factor (anti-TNF) agents remain the biologic cornerstone for this indication; however, many patients either fail to respond initially or experience secondary loss of response, requiring alternative strategies. Vedolizumab, a humanized monoclonal antibody selectively antagonizing the α4β7 integrin on gut-homing lymphocytes, has demonstrated robust efficacy for luminal Crohn's disease, yet its effectiveness for perianal fistula healing has not been systematically synthesized.
Aims & Methods
We aimed to determine the pooled rate of complete perianal fistula closure with vedolizumab in patients with fistulizing CD. We conducted a systematic review and meta-analysis in accordance with PRISMA 2020 guidelines. PubMed/MEDLINE, Embase, Cochrane CENTRAL, and LILACS were searched from January 2014, corresponding to vedolizumab's initial regulatory approval, through March 2025. Eligible studies enrolled adults (≥18 years) with confirmed CD and active perianal fistula receiving vedolizumab therapy and reported rates of complete fistula closure. Two independent reviewers performed study selection and data extraction. Methodological quality was assessed using RoB 2 and ROBINS-I. Pooled proportions were calculated using DerSimonian–Laird random-effects models with logit transformation. Heterogeneity was quantified by Cochran's Q, I², and τ². Publication bias was assessed by funnel plot asymmetry and Egger's regression test. Sensitivity analyses used leave-one-out methodology.
Results
Six studies comprising a total of 295 patients with perianal fistulizing CD treated with vedolizumab met inclusion criteria. Study designs included two RCTs or post-hoc RCT analyses and four observational cohort studies, with publication years ranging from 2018 to 2025. Individual study fistula closure rates ranged from 0% (Newman et al., 2023) to 47.4% (Shani et al., 2025). The pooled proportion of complete perianal fistula closure was 37.1% (95% CI: 26.6%–48.9%) using the random-effects model. Substantial between-study heterogeneity was observed (I² = 65.5%; Cochran's Q = 14.48, df = 5, p = 0.013; τ² = 0.2098). Leave-one-out sensitivity analysis demonstrated robustness of the primary estimate, with pooled proportions ranging from 33.9% to 43.5% upon sequential omission of individual studies. Omission of the Chapuis-Biron 2020 study—the largest included study using the most stringent composite outcome definition—completely eliminated statistical heterogeneity (I² = 0.0%; pooled estimate 43.5%, 95% CI: 36.3%–51.1%). Egger's regression test revealed no significant publication bias (intercept = −0.09, p = 0.387).
Conclusion
Vedolizumab achieves complete perianal fistula closure in approximately 37% of patients with fistulizing Crohn's disease, a rate broadly comparable to those reported for anti-TNF agents. These findings are robust across sensitivity analyses and support vedolizumab as a viable therapeutic option, particularly in patients with prior anti-TNF failure or intolerance. The substantial heterogeneity observed underscores the need for standardized fistula outcome definitions in future trials. Prospective head-to-head comparative studies are warranted to refine the positioning of vedolizumab within the therapeutic algorithm for perianal fistulizing Crohn's disease.
References
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