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P491 INSPIRE: design and implementation aspects of a registry of complex perianal fistulas in Crohn’s disease patients treated with darvadstrocel

O. Zmora*1, J. Panés2, C. Drohan3, J. M. Khalid4, S. Campbell-Hill4, C. Agboton5

1Assaf Harofeh Medical Center, Tel Aviv University, Department of Surgery, Tel Aviv, Israel, 2Hospital Clínic de Barcelona, Gastroenterology Department, Barcelona, Spain, 3Patient Advisor, County Dublin, Ireland, 4Takeda Development Centre, London, UK, 5Takeda Pharmaceuticals International AG, Zurich, Switzerland

Background

Perianal fistulas (PAF) are a common presentation of Crohn’s disease (CD), the majority being complex (CPAF).1–4 Existing medical and surgical therapies for CPAF have low long-term success rates.4,5 Darvadstrocel (DVS) is a mesenchymal stem cell (MSC) therapy that demonstrated efficacy and tolerability in patients with CPAF over 52 weeks,4 and is the first MSC therapy centrally approved in Europe for the treatment of CPAF.6 However, real-world and longer-term effectiveness data for DVS are lacking. This abstract describes the development of a DVS registry aiming to establish a framework to capture real-world clinical effectiveness and safety data. (EU PAS Register Number: EUPAS24267).

Methods

The INSPIRE registry aims to establish a data collection framework to capture real-world data on all patients treated with DVS for CPAF over 36 months. Data on patient selection, concomitant treatment, surgical technique, fistula response, remission and complications will be captured and associations between practice parameters and outcome will be assessed.

Results

An observational, multi-national, open-enrolment registry was set up to record all patients treated with DVS for CPAF. Ensuring enrolment of almost 100% of patients treated is required for sufficient longer-term evaluation of DVS and to support value-based reimbursement requests in some countries. The made to order manufacturing process and traceability lends itself to more complete data capture. The goal of this registry is to improve understanding of disease presentation, patient characteristics, treatment patterns and clinical outcomes. The primary outcomes of INSPIRE are clinical response (a reduction in ≥50% of draining PAF) and clinical remission (closure of all treated PAF on physical examination).1,7 Health-related quality of life, patient-reported outcomes and MRI images will be collected. INSPIRE will attempt to enrol ≥1600 patients, establishing the largest CPAF database. Patient engagement will be facilitated using digital solutions where possible. Data will be reviewed by the Steering Committee who will act in an independent advisory capacity to provide scientific oversight and to evaluate the effectiveness and safety of DVS. The first patient was treated with DVS on 21 June 2018. The first site initiation visit was conducted on 31 October 2018.

Conclusion

INSPIRE will be the first registry to collect data assessing the effectiveness and safety of DVS in patients with CPAF. A comprehensive set of parameters will be collected and correlated, to better understand appropriate patient selection and surgical approach. Patient-centric features of the DVS registry are continuing to be explored.

References

1. Panés J, García-Olmo D2, Van Assche G et al. Expanded allogeneic adipose-derived mesenchymal stem cells (Cx601) for complex perianal fistulas in Crohn’s disease: a phase 3 randomised, double-blind controlled trial. Lancet 2016;388:1281–90.

2. Silverberg MS, Satsangi J, Ahmad T, et al. Toward an integrated clinical, molecular and serological classification of inflammatory bowel disease: report of a Working Party of the 2005 Montreal World Congress of Gastroenterology. Can J Gastroenterology 2005;19(Suppl. A):5A–36A.

3. Panés J, García-Olmo D, Van Assche G, et al. Long-term efficacy and safety of stem cell therapy (Cx601) for complex perianal fistulas in patients with Crohn’s disease. Gastroenterology 2018;154:1334–1342.e4

4. Sandborn WJ, Fazio VW, Feagan BG, et al. AGA technical review on perianal Crohn’s disease. Gastroenterology 2003;125:1508–30.

5. Kotze PG, Shen B, Lightner A, et al. Modern management of perianal fistulas in Crohn’s disease: future directions. Gut 2018;67:1181–1194.

6. European Medicines Agency (EMA) Committee for Medicinal Products for Human Use. Alofisel, INN-darvadstrocel EPAR Annex I Summary of Product Characteristics. https://www.ema.europa.eu/documents/product-information/alofisel-epar-product-information_en.pdf

7. Present DH, Rutgeerts P, Targan S, et al. Infliximab for the treatment of fistulas in patients with Crohn’s disease. N Engl J Med 1999;340:1398–405.