DOP77 Mesenchymal stem cell therapy for refractory Crohn’s perianal fistulas: a case series

Abstract

Abstract Background Nearly one-third of patients with Crohn’s disease will develop one or multiple perianal fistulas within the first two decades after diagnosis, with the majority being complex. Treatment options are limited with high recurrence rates after both medical and surgical approaches. It has been demonstrated that a completely fibrotic tract on Magnetic Resonance Imaging (MRI) with a MAGNIFI-CD <6 is the best predictor for long-term clinical closure. Mesenchymal stem cell treatment (MST) has emerged as a new therapeutic strategy for these fistulas. The aim of the current study was to analyse the effectiveness of MST for complex Crohn’s perianal fistulas based on MRI. Methods Consecutive patients with complex Crohn’s perianal fistulas, previously failing both anti-TNF treatment and surgical closure, that underwent surgical closure of the internal opening with MST between December 2019 and March 2023 were included. All patients underwent a MRI preoperatively and between three to six months after MST. For the current study, MRI’s were read by an senior radiologist. The primary endpoint was radiological remission of the fistula(s) defined as a MAGNIFI-CD <6 on MRI. Secondary endpoints were clinical closure (defined as closure of the external opening(s)), recurrence rate, change of MAGNIFI-CD over time, quality of life based on the perianal disease activity index (PDAI), and serious adverse events (SAE). Results In total, 30 patients (16 females) with 48 fistula tracts were included with a median clinical follow-up of 20 months. Radiological remission was achieved in thirteen patients (43.3%) after a median follow-up of 5.0 months (IQR 3.0-6.0). The median MAGNIFI-CD at baseline was 15.0 (IQR 7.0-20.0) which decreased significantly to 8.0 (IQR 3.0-15.0) after treatment (p= 0.001). Clinical closure of the fistula(s) was achieved in 21 patients (70.0%). Three patients (14.3%) developed a recurrence during long-term FU. All three patients had clinically closed fistula(s), but no radiological remission. The median PDAI decreased significantly from 10.5 (IQR 7.0-14.0) to 4.0 (IQR 0.0-7.3) (p= 0.001). Overall, in this patient group one SAE occurred requiring multiple reinterventions and temporary stoma. Conclusion Closure of the internal fistula opening with MST is a promising treatment strategy for therapy refractory Crohn’s perianal fistulas, resulting in >40% radiological remission and clinical closure in 70%. No recurrences were seen in patients with radiological remission. MST was also associated with a significant increase in quality of life. Further research is needed to gain insight in which patients MST is most likely to induce radiological remission.