Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Meta-Analysis
. 2025 Apr;13(3):416-426.
doi: 10.1002/ueg2.12673. Epub 2024 Oct 3.

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

Carlos Taxonera  1 , Miguel A García-Brenes  1 , David Olivares  2 , Olga N López-García  1 , Raúl Zapater  1 , Cristina Alba  1
Affiliations
Meta-Analysis

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

Carlos Taxonera et al. United European Gastroenterol J. 2025 Apr.

Abstract

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.

Keywords: Crohn's disease; adipose‐derived allogenic mesenchymal stem cells; alofisel; darvadstrocel; inflammatory bowel disease; meta‐analysis; perianal fistulas.

PubMed Disclaimer

Conflict of interest statement

Carlos Taxonera has served as a speaker, consultant, and advisory board member for MSD, AbbVie, Pfizer, Takeda, Galapagos, Lilly, Fresenius Kabi, Ferring, Faes Farma, Shire Pharmaceuticals, Dr. Falk Pharma, and Tillots. These activities were not related to the present work. The remaining authors have no conflicts of interest to declare.

Figures

FIGURE 1
FIGURE 1
PRISMA flow diagram of the study selection. CD, Crohn's disease.
FIGURE 2
FIGURE 2
(a) Clinical remission rate at month 6. (b) Clinical remission rate at month 12. Random‐effects model was applied. CI, confidence interval; ES, effect size; R, remission. [Correction added on 21 October 2024, after first online publication: Figure 2 has been updated.]
FIGURE 3
FIGURE 3
(a) Failure rate at last follow‐up (mean follow‐up of 18, 7 months; SD 9.9). Random‐effects model was applied. (b) Beta regression model between time of last follow‐up (mean, months) and failure rate (%). Coefficient = −0.07, p = 0.85, pseudo‐R2 = 0.003. CI, confidence interval; ES, effect size.
FIGURE 4
FIGURE 4
(a) Adverse events incidence rate per 100 patients‐year (PY). (b) Serious adverse events incidence rate per 100 PY. (c) Perianal abscess incidence rate per 100 PY. (d) Reoperation incidence rate per 100 PY. Random‐effects model was applied. CI, confidence interval. [Correction added on 21 October 2024, after first online publication: Figure 4 has been updated.]
See this image and copyright information in PMC

References

    1. Schwartz DA, Loftus EV, Jr , Tremaine WJ, Panaccione R, Harmsen W, Zinsmeister AR, et al. The natural history of fistulizing Crohn’s disease in Olmsted County, Minnesota. Gastroenterology. 2002;122(4):875–880. 10.1053/gast.2002.32362 - DOI - PubMed
    1. Göttgens KW, Jeuring SF, Sturkenboom R, Romberg‐Camps MJ, Oostenbrug LE, Jonkers DM, et al. Time trends in the epidemiology and outcome of perianal fistulizing Crohn’s disease in a population‐based cohort. Eur J Gastroenterol Hepatol. 2017;29(5):595–601. 10.1097/meg.0000000000000840 - DOI - PubMed
    1. Taxonera C, Schwartz DA, García‐Olmo D. Emerging treatments for complex perianal fistula in Crohn's disease. World J Gastroenterol. 2009;15(34):4263–4272. 10.3748/wjg.15.4263 - DOI - PMC - PubMed
    1. Torres J, Bonovas S, Doherty G, Kucharzik T, Gisbert JP, Raine T, et al. ECCO guidelines on therapeutics in Crohn’s disease: medical treatment. J Crohns Colitis. 2020;14(1):4–22. 10.1093/ecco-jcc/jjz180 - DOI - PubMed
    1. Sands BE, Anderson FH, Bernstein CN, Chey WY, Feagan BG, Fedorak RN, et al. Infliximab maintenance therapy for fistulizing Crohn's disease. N Engl J Med. 2004;350(9):876–885. 10.1056/nejmoa030815 - DOI - PubMed

MeSH terms