Longitudinal Registry of Difficult-to-Treat Inflammatory Bowel Disease

DTT-IBD PLATFORM is a multicentre, investigator-initiated, ambidirectional observational patient registry designed to characterize difficult-to-treat inflammatory bowel disease across its full longitudinal course.

The registry uses a layered cohort structure. First, eligible adult patients with confirmed inflammatory bowel disease are identified from participating-centre clinical databases and longitudinal medical records. Second, patients exposed to advanced therapies form a longitudinal treatment cohort in which treatment initiation, optimization, discontinuation, treatment failure, mechanism transitions, objective reassessment, and subsequent outcomes can be reconstructed. Third, patients meeting prespecified operational criteria for DTT-IBD enter the DTT registry layer irrespective of the specific DTT domain through which they qualify.

DTT-IBD status will be determined using prespecified operational definitions based on international consensus concepts and will include medical treatment failure as well as relevant postoperative, complex perianal, pouch-related, structural, and psychosocial/implementation domains. Treatment discontinuation or switching alone will not automatically be considered efficacy failure; the underlying reason and supporting objective evidence will be recorded whenever available.

The retrospective component will reconstruct eligible longitudinal data from existing medical records using the same core data dictionary applied prospectively. The prospective component will consecutively enroll eligible participants and continue longitudinal follow-up. Data sources may include outpatient and inpatient records, laboratory results, endoscopy, intestinal ultrasound and cross-sectional imaging, therapeutic drug monitoring, advanced-therapy administration, multidisciplinary team records, surgical procedures, hospitalizations, and routine follow-up records.

The study does not assign or mandate any drug, dose, diagnostic examination, surgical procedure, or treatment strategy. All clinical management is determined through routine clinical care and shared decision-making.

An optional biospecimen subcohort may collect blood, stool, and clinically obtained residual intestinal tissue from prospectively consented participants. Biospecimen participation is not required for participation in the clinical registry, and no research-only endoscopy or surgical tissue acquisition is mandated by the registry.

The platform is intended to support prespecified nested analyses including: longitudinal development of DTT-IBD after advanced-therapy initiation; transitions between active, controlled, and reactivated DTT states; cumulative time under objectively uncontrolled disease; treatment-failure mechanisms and subsequent management decisions; irreversible bowel damage; treatment persistence; hospitalization and surgery; and implementation of multidisciplinary care. Detailed hypotheses, exposure definitions, estimands, analytic time zero, and statistical analysis plans for major nested studies will be prospectively specified before the corresponding analyses are performed.

Quality assurance procedures include source-level reconciliation of key events, standardized operational definitions, a common data dictionary, duplicate-patient resolution, predefined rules for missing or indeterminate disease states, audit trails for manually adjudicated events, and periodic data-quality checks across participating centres.