Dis Colon Rectum. 2022 May 1;65(5):713-720.doi: 10.1097/DCR.0000000000002325.

Damián Garcia-Olmo ¹, Inmaculada Gilaberte ², Matthias Binek ³, André J L D Hoore ⁴, Dirk Lindner ³, Francesco Selvaggi ⁵, Antonino Spinelli ^6 7, Julian Panés ⁸

Author information

¹Universidad Autónoma de Madrid, Fundación Jiménez Díaz, University Hospital, Madrid, Spain.

²Takeda Pharmaceuticals S.L., Madrid, Spain.

³Takeda Pharmaceuticals International AG, Zurich, Switzerland.

⁴Universitair Ziekenhuis Leuven, Leuven, Belgium.

⁵Colon and Rectal Surgery Unit, Department of Advanced Medical and Surgery Sciences, Luigi Vanvitelli University, Naples, Italy.

⁶Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy.

⁷IRCCS Humanitas Research Hospital, Division of Colon and Rectal Surgery, Rozzano Milan, Italy.

⁸Inflammatory Bowel Disease Unit, Hospital Clínic de Barcelona, IDIBAPS, CIBERehd, Barcelona, Spain.

Abstract

Background: Darvadstrocel is an expanded allogeneic adipose-derived mesenchymal stem cell therapy for the treatment of complex perianal fistulas in patients with Crohn's disease. Safety and efficacy outcomes from the clinical trial known as "Adipose derived mesenchymal stem cells for induction of remission in perianal fistulizing Crohn's disease," or ADMIRE-CD (NCT01541579), from up to 52 weeks posttreatment were previously reported. Here, the outcomes from an extended 104-week follow-up are reported.

Objective: The goal of this study was to assess the long-term safety and efficacy of darvadstrocel at 2 years post-treatment in patients with Crohn's disease and complex perianal fistulas.

Design: This was a phase 3 double-blind randomized controlled study (ADMIRE-CD) in patients with perianal fistulizing Crohn's disease.

Settings: This study extension was conducted in multiple hospitals across 7 European countries and Israel.

Patients: Forty patients entered the extended follow-up period: 25 patients in the darvadstrocel treatment group and 15 in the control group.

Interventions: Darvadstrocel or saline solution (control group) was administered once, locally, after fistula tract curettage and internal opening closure (with previous seton placement). All patients were permitted to continue ongoing medical treatments for fistulas.

Main outcome measures: Treatment-emergent serious adverse events were recorded through week 104. Clinical remission, defined as closure of all treated external openings that were draining at baseline despite gentle finger compression, was assessed at week 104.

Results: Of 40 patients, 37 completed the extended follow-up. Through week 104, 7 treatment-emergent serious adverse events were reported, of which 4 occurred between weeks 52 and 104. At week 104, clinical remission was reported in 14/25 (56%) patients in the darvadstrocel group and 6/15 (40%) patients in the control group.

Limitations: Limitations include the small number of patients who entered the extended follow-up period, and no imaging examinations were performed at the 104-week time point.

Conclusions: Darvadstrocel was well tolerated and clinical remission after treatment with darvadstrocel may be sustained for up to 104 weeks in patients with perianal fistulizing Crohn's disease. See Video Abstract at http://links.lww.com/DCR/B812.ClinicalTrials.gov No: NCT01541579.