Darvadstrocel for Complex Perianal Fistulas in Japanese Adults with Crohn’s Disease: A Phase 3 Study

Abstract

Background and Aims Previous studies conducted in Europe suggested that darvadstrocel, a suspension of expanded allogeneic adipose-derived mesenchymal stem cells, is safe and effective for treatment-refractory complex perianal fistulas in patients with Crohn’s disease. The aim of this study was to evaluate the efficacy and safety of darvadstrocel for the treatment of complex perianal fistulas in Japanese adults with Crohn’s disease. Methods This is a phase 3, open-label, single-arm study conducted at 9 sites in Japan. Adult patients with non-active or mildly active Crohn’s disease and complex perianal fistulas received a single 24mL intralesional injection of darvadstrocel (120×10 6 cells). The primary endpoint was combined remission (clinically confirmed closure of all treated external openings that were draining at screening and absence of collections >2 cm [confirmed by magnetic resonance imaging] among treated fistulas) at Week 24. Results Between March 6, 2019 and February 1, 2021, 22 patients received darvadstrocel and completed the 52-week follow-up. The proportion of patients achieving combined remission at Week 24 was 59.1% (95% CI, 38.5–79.6). The effect was maintained at Week 52, with 68.2% (95% CI, 48.7–87.6) of patients achieving combined remission. Treatment-related adverse events included: 1 (4.5%) patient with worsening of Crohn’s disease and diarrhea and 1 (4.5%) patient with blood bilirubin increase. No new safety findings were identified in this study. Conclusions The efficacy and tolerability of darvadstrocel in Japanese adult patients with treatment-refractory complex perianal fistulas in Crohn’s disease were similar to those observed in the previous European study.

Allogenic stem cells for anal Crohn’s fistula: treating early improves the deep response rate

“…Although in ammatory tracts improved in two thirds of the cases by MRI, deep response was observed in only one third of patients. Our results are similar to those of certain previous studies [12,13] but less favorable than those for others [14]. These differences could be explained by a more severe stula pro le (multi-operated, "old", multibranched, associated with anal stricture, in failure of a previous obturation technique in 1/3 of cases) and stronger criteria to analyze the response.…”

“…These results led to marketing authorization in Europe and their commercialization (darvadstrocel, Takeda company) in France since 2020. To date, evaluations of this treatment in real-life situations are still limited [12][13][14]. Our objective was to collect data from the initial experience in France in 2 tertiary centers with at least one year of clinical and radiological follow-up.…”

Allogenic stem cells for Crohn's anal fistulas: Treating early improves the deep remission rate

“…Our results are like those of certain previous studies [12, 13] but less favourable than those for others [14]. These differences could be explained by a more severe fistula profile (multioperated, “old”, multibranched, associated with anal stricture, in failure of a previous obturation technique in 1/3 of cases) and stronger criteria to analyse the response.…”

“…This rate was 33.6% in the German study of Schwandner [13] and 18.2% in the Japanese study of Furukawa et al. [14]. Regarding the long‐term safety profile, the limited number of patients and the short duration of follow‐up in our series did not allow any formal conclusions to be drawn.…”

Stammzelltherapie bei komplexen perianalen Fisteln bei Morbus Crohn: Aktuelle Evidenz und Ausblick

“…Im Rahmen des 52-Wochen-Follow-up zeigte sich eine kombinierte Remission (klinisch und MR-morphologisch) bei 68,2% der Patienten, unerwünschte Ereignisse traten bei 2 Patienten auf (Aggravation des Morbus Crohn mit Diarrhö; laborchemischer Bilirubinanstieg). Die Autoren schlussfolgerten, dass im Rahmen der Phase-III-Studie die Darvadstrocel-Injektion eine effektive und sichere Therapieoption bei komplexen perianalen Fisteln bei Morbus Crohn darstellt [30].…”