P351 Allogenic adipose-derived mesenchymal stem cells (darvadstrocel) in Japanese patients with complex perianal fistulas in Crohn’s disease
WatanabeDirector of division- Assistan, K.(1);Mizushima, T.(2);Okita, Y.(3);Sugita, A.(4);Nakaya, R.(5);Shibata, M.(5);Yamaguchi , T.(5);
(1)Hyogo College of Medicine, Center for Inflammatory Bowel Disease- Division of Internal Medicine, Hyogo, Japan;(2)Osaka University Graduate School of Medicine, Department of Therapeutics for Inflammatory Bowel Diseases, Osaka, Japan;(3)Mie University Graduate School of Medicine, Department of Gastrointestinal and Pediatric Surgery- Division of Reparative Medicine- Institute of Life Sciences, Mie, Japan;(4)Yokohama Municipal Citizen's Hospital, Department of Inflammatory Bowel Disease, Yokohama, Japan;(5)Takeda Pharmaceutical Company Limited, Takeda Development Center, Osaka, Japan;
Background
Patients with complex Crohn’s perianal fistulas were treated with allogenic mesenchymal stem cells (darvadstrocel) in pivotal studies, and in clinical practice in Europe since 2018. However, it is unclear whether the same efficacy and safety could be expected across different ethnic groups. Moreover, it is known that perianal complications including perianal fistulas are more frequent in Asian patients with Crohn’s disease (CD).
Methods
Japanese adult patients with treatment-refractory complex perianal fistulas in CD were enrolled from 9 sites in a phase 3, open-label, single-arm, uncontrolled study. Patients could have 2 internal and 3 external openings at maximum, and their luminal disease was non-active or mildly active (CDAI ≤220) at baseline. A single dose (24mL, 120 million cells) of darvadstrocel was intralesionally injected, and results after 24 and 52 weeks were evaluated. Primary endpoint was combined remission (a remission rate evaluated clinically and by MRI) at Week 24.
Results
22 patients (mean age 36.4 years, 63.6% male, mean duration of CD 11.3 years) were enrolled. A half (11/22) had 1 internal opening (IO) and 2 external openings (EO) followed by 1IO-1EO/2IO-2EO/2IO-3EO (3 each, 9/22) and 1IO-3EO (2/22). 59.1% and 68.2% achieved combined remission at Week 24 (primary endpoint) and Week 52, respectively.
Up to Week 52, 90.9% (20/22) experienced adverse events (AE), and 81.8% (18/22) were mild or moderate in intensity. Proctalgia (6/22), nasopharyngitis (5/22), and anal fistula (4/22) were most frequently reported. There was no death or AE-related study discontinuation.
| Darvadstrocel (n=22) | ||
|---|---|---|
| % (n) | 95% CI | |
| Combined remissiona | ||
| W24 | 59.1 (13/22) | (38.5, 79.6) |
| W52 | 68.2 (15/22) | (48.7, 87.6) |
| Clinical remissionb | ||
| W24 | 59.1 (13/22) | (38.5, 79.6) |
| W52 | 72.7 (16/22) | (54.1, 91.3) |
| Responsec | ||
| W24 | 81.8 (18/22) | (65.7, 97.9) |
| W52 | 90.9 (20/22) | (78.9, 100.0) |
| Relapsed | ||
| W24 | 25.0 (4/16e) | (3.8, 46.2) |
| W52 | 23.1 (3/13f) | (0.2, 46.0) |
| Median (week) | ||
| Time to clinical remission | 3.77 | (2.0, 15.6) |
| Time to response | 2.6 | (1.7, 4.3) |
a: Clinically confirmed closure (CCC) of all treated EOs (ATE), and the absence of collections >2 cm confirmed by MRI
b: CCC of ATE
c: CCC of at least 50% of ATE
d: Clinically confirmed reopening, or a collection >2 cm confirmed by MRI
e: Number of clinical remission at previous visit
f: Number of combined remission at W24
Conclusion
52 weeks after administrating darvadstrocel in Japanese patients with complex perianal fistulas in CD, fistula closure was confirmed in 68% (15/22) and partial closure in 90.0% (20/22). These findings are consistent with the pivotal study ADMIRE-CD, and real-world case-series reported from Europe. Furthermore, no new safety concerns were identified.