Darvadstrocel for complex perianal fistulas in Crohn's disease: A systematic review and meta-analysis.

Background: Local injection of darvadstrocel, a suspension of expanded adipose-derived allogenic mesenchymal stem cells, has been used for treatment-refractory perianal fistulas in Crohn's disease (CD).

Objective: This study aimed to investigate efficacy and safety of darvadstrocel for complex perianal fistulas in CD.

Methods: A systematic search was conducted through April 2024 in relevant databases for observational studies evaluating darvadstrocel. A random-effects meta-analysis model was used to calculate the pooled effect sizes (proportions or incidence rates [IRs]) with 95% confidence intervals (CIs) of effectiveness and safety outcomes. The risk of bias was evaluated using the Joanna Briggs Institute Critical Appraisal Tool. The I² value assessed heterogeneity. Sensitivity and subgroup analyses were also conducted.

Results: Twelve studies were included with 595 patients. The pooled rate of patients achieving clinical remission, defined as fistula healing, was 68.1% at month 6 (95% CI 63.4-72.7) and 77.2% (95% CI 70.1-83.8) at month 12. Combined remission, defined as clinical remission and absence of collections >2 cm confirmed by magnetic resonance imaging, was reported in 60.6% and in 69.7% of patients at months 6 and 12, respectively. The rate of patients with treatment failure, defined as no clinical remission at the last follow-up (mean 18.7 months; SD 9.9), was 34.5%. Failure rate was independent of follow-up time (p = 0.85). For effectiveness outcomes, between-study heterogeneity was negligible. Subgroup analysis indicated that none of the covariates modified the treatment effect. Pooled IRs per 100 patient-years of adverse events (AE), serious AEs, perianal abscesses, and reoperations were 19.6, 3.2, 16.9 and 7.1, respectively.

Conclusion: Evidence from observational studies supports the efficacy and safety of darvadstrocel for complex perianal fistulas in CD. Studies have reported high fistula healing rates that can be sustained long-term in most patients, with negligible between-study heterogeneity, as well as a favorable safety profile.