Abstract Background Complex perianal fistulas represent one of the most challenging manifestations of Crohn’s disease. Combined surgical and biological therapy remains first-line, yet healing rates stay below 60%1. Autologous microfragmented adipose tissue (M-Fat) injection has recently shown promising results: a non-profit prospective pilot study on 15 patients reported a 66.7% rate of combined remission in multiresistant complex fistulizing Crohn’s disease (PCD) patients treated with M-Fat2. M-Fat injection is minimally invasive, with less risk of sphincteric damage and can be carried out in day-surgery setting. The primary aim of this multicentre double-blind RCT (ATTIC) is to evaluate the efficacy of M-Fat infiltration in the healing of perianal complex fistulas not-responding to biologics. Methods Consecutive patients with persistent complex fistulizing PCD refractory to biosurgical approach were assessed for eligibility in 6 centers. After baseline pelvic MRI, included patients were submitted to surgical drainage with “cone-like” fistulectomy, and randomized to receive, at the internal orifice level and along fistula tracts, either 15-20 cc local M-Fat injection (treatment group) or a suture placement and of 15 cc saline injection (control group). Clinical follow-up were conducted at 2, 4, 8, 12, and 24 weeks; at 24 weeks after surgery, pelvic MRI was obtained. Success was defined as “combined remission”, combination of clinical (no drainage upon gentle finger compression) and radiological healing (no residual collections 3 mm). Clinical remission was defined as clinical healing of all external openings not confirmed at radiological assessment. Results A total of 66 patients (33 per group) completed the 24-week follow-up. Combined remission rate was significantly higher in treatment group (57.6% vs 18.2%; p = 0.002) and clinical remission was significantly higher in treatment group (78.8% vs 54.5%; p = 0.037). Both groups showed significant improvements in quality-of-life scores and CRP levels from baseline, with no between-group differences at 24 weeks, except for Work Productivity and Activity Impairment (WPAI) presenteeism subscore. Adverse events (AEs) were reported in 10% (3/33) of patients in the treatment group and 8.1% (2/33) in the control group. Serious AEs occurred in 1 (3%) treated patient and 2 (6%) controls with no statistically significant differences between groups. Conclusion Intraoperative M-Fat injection, associated with surgical complete drainage of perianal sepsis, is safe, effective, and reproducible in healing complex multirefractory perianal fistulas, while improving the quality of life and significantly reducing the risk of definitive oostomy. References: 1. Guillo L, Gravier Dumonceau R, Vélier M, et al. Efficacy of mesenchymal stem cell-based therapies in the treatment of perianal fistulizing Crohn’s disease: a systematic review and meta-analysis. Stem Cell Res Ther. Mar 28 2025;16(1):152. doi:10.1186/s13287-025-04272-y 2. Laureti S, Gionchetti P, Cappelli A, et al. Refractory Complex Crohn’s Perianal Fistulas: A Role for Autologous Microfragmented Adipose Tissue Injection. Inflamm Bowel Dis. Jan 6 2020;26(2):321-330. doi:10.1093/ibd/izz051 Conflict of interest: Laureti, Silvio: No COI Sofo, Luigi: No conflict of interest Cappelli, Alberta: No conflict of interest Colombo, Francesco: No conflict of interest Luglio, Gaetano: No conflict of interest Scaringi, Stefano: No conflict of interest Isopi, Claudio: No conflict of interest Sacchetti, Franco: No conflict of interest Clerico, Giuseppe: No conflict of interest Danelli, Piergiorgio: No conflict of interest Cricrì, Michele: No conflict of interest Perna, Federico: No conflict of interest Gentilini, Lorenzo: No conflict of interest Dr. Menon, Alessandra: Consultat for Lipogems International SpA (Clinical trial coordinator and statistician) Gionchetti, Paolo: No conflict of interest Spinelli, Antonino: No conflict of interest
Laureti et al. (Thu,) studied this question.