P1113 Efficacy and safety of Darvadstrocel (allogeneic stem cell therapy) at 6 and 12 months in refractory complex perianal fistulas in Crohn’s disease. Real clinical practice in the Northwest of Spain
Authors: De Castro Parga M L , Varela A , Fernandez-Salgado E , Vigorita V , López-De los ríos R , Hernández V , Molina G , Barreiro E , Seoane J , Otero M , Gallego J C , Romero G , Carpio D , Echarri A , Rodriguez-Prada I 
Published: January 2025

Abstract

Background
Refractory complex perianal fistulas remain a difficult and demanding problem in patients with Crohn’s disease. Perianal disease is associated with high healthcare costs and reduced patient-perceived quality of life. Based on an adequate efficacy and safety profile, Darvadstrocel (allogeneic expanded adipose tissue-derived stem cells) is a novel therapy that was approved for this indication in 2018. This article summarizes the clinical experience with this therapy in 3 hospitals in northwestern Spain.

Methods
Observational, multi-center and prospective cohort study carried out in 3 hospitals in Galicia (northwestern Spain) from November 2019 to June 2024. Eligibility criteria were patients with non-active/mildly active luminal Crohn´s Disease and active perianal complex fistulas with 1-3 outer and 1-2 inner orifices and failed conventional and anti-TNF therapy. Inactive rectal disease and absence of perianal collections ≥ 2 cm had to be confirmed by endoscopy and pelvic MRI at the time of surgery. Combined success at 6 and 12 months were defined as complete clinical closure (100% of outer orifices) and radiographic findings (no fluid collection ≥2cm). Data are presented as median and interquartile range, and non-parametric tests were used for statistical analysis.

Results
25 patients were included: women 56% (14), median age 39 (28-47), time since perianal fistula diagnosis 8 (5-14) years. Baseline demographics for the cohort are summarized in Table 1. Previous need for health care due to perianal disease was high: emergency consultations 4 (1-8), hospital admissions 2 (0.5-5), surgical interventions 3 (1-5.5). Darvadstrocel was administered in 18 transsphincteric (64%) and 10 intersphinteric perianal fistulas. Five patients experienced mild adverse events shortly after treatment (20%): 3 had local pain, and 2 local abscess. At 6 months complete clinical closure of fistulas reached 71% (17/24) and combined success 69% (16/23). At 12 months complete clinical closure was 76,6%/ (16/ 21) and combined success 76% (15/21) A shorter interval between the fistula conditioning surgery time and the stem cells administration surgery time was associated with greater combined success at 6 and 12 months, and complete clinical closure at 12 months (p&lt;0.05). No long-term adverse events were reported.

Conclusion
This study supports the efficacyand safety of Darvadstrocell for refractory perianal CD fistulas with combined success rates of 69% and 76% at 6 and 12 months.
Technical and individual characteristics for a better outcome remain unknown, but a shorter interval between surgical times was associated with greater response.

References
Taxonera C, García-Brenes MA, Olivares D et al. Darvadstrocel for complex perianal fistulas in Crohn´s disease. A systematic review and meta-analysis. United European Gastroebnterol J 2024; Oct 3 doi 10.1012/ueg2.12673
Herreros MD, Ramirez JM, Otero-Piñeiro A et al. Use of Darvadstrocel for complex Crohn´s fistulas in real clinical practice. The national project to implement mesenchymal stem cell for the treatment of perianal Crohn´s disease (The PRIME study). Diseases colon and rectum 2024; 67(7) 960-967.