Sponsors decision

The main aim is to learn about the risk of cancer after treatment with darvadstrocel compared to other standards of care in people with Crohn's Disease (CD).

In this study, the study doctors will review each participant's past medical records. This study is about collecting existing information only; participants will not receive treatment or need to visit a study doctor during this study.

This is a retrospective, non-interventional study of participants with complex perianal fistula in Crohn's disease (CPF-CD). This study will assess tumorigenicity risk and all-cause and cancer-specific mortality in participants with darvadstrocel.

The study will enroll approximately 5850 participants. Data will be collected retrospectively from European secondary data sources. Participants will be assigned to two cohorts:

• Darvadstrocel cohort
• Matched control cohort: Alternate SoC.

This multi-center trial will be conducted in France, Germany, Netherlands, and Spain. The overall duration of the study will be approximately 96 months, including index period (the time in which eligible participants are included in the study) and 12 months follow-up period.

Inclusion Criteria:

Darvadstrocel cohort 1. Participants will be included in the darvadstrocel cohort if they have at least one record of prescription/dispensation/administration of darvadstrocel at some point during the study period.

Comparator cohort

1. A comparator cohort of controls (matched control cohort) will be composed of participants with CD and PF randomly selected from a pool of eligible participants with no history of administration of darvadstrocel.

Exclusion Criteria:

1. Has less than 12 months of uninterrupted data within country-specific data source prior to index date.
2. Has not meet quality indicators for country-specific data source (if applicable).
3. Has diagnosis of cancer prior different from non-melanoma skin cancer to index date. This will minimise the misclassification of prevalent or metastatic cancer as incident cases for the analysis of the study objectives.
4. Has diagnosis of ulcerative colitis at any point during the study period and medical history period. This will avoid potential ascertainment bias as there is currently no gold standard for differential diagnosis in IBD. Approximately 5 percent (%) to 15% of cases do not meet strict criteria for either ulcerative colitis (UC) or CD and in up to 14% of participants classified as UC and CD, the diagnosis changes over time.
5. Has record of proctectomy or colectomy prior to index date. Proctectomy and colectomy are considered "last chance" surgery options for anal fistulas or other complications of CD. These participants are not the target population for darvadstrocel. They would not be eligible for darvadstrocel administration and loss of their gastrointestinal tract would affect the risk of colorectal cancer; the most common cancer associated with CD.

Participants diagnosed with CPF-CD who have been administered at least one dose of darvadstrocel and participants with CD and perianal fistula (PF) and no history of administration of darvadstrocel.

Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.

IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.