P0892 Real-life vs clinical trial access to biological therapy: findings from an Italian-American study on inflammatory bowel disease
Authors: Di Vincenzo F , Principessa C , Ioannou S , Capobianco I , Gasbarrini A , Laterza L , Abreu M T , Scaldaferri F 
Published: January 2025

Background

Treatment goals in IBD have shifted from symptom control to mucosal healing and prevention of complications, as well as enhancing quality of life and reducing disability as proposed by the STRIDE II initiative1. Despite pharmacological advances, up to 50% of IBD patients present non-response to currently available advanced therapies (ADT), highlighting the need for alternative therapeutic options offered in randomized clinical trials (RCTs). However, strict eligibility criteria may reduce the access of real-life IBD populations to RCTs. This study aims to evaluate the percentage of eligibility and the representativeness of real-life IBD population in RCTs, deeply investigating the most under respected criteria responsible for patients’ exclusion from RCTs as well as clinical characteristics which distinguish eligible and ineligible patients, thereby suggesting new population clusters for future RCTs development.

Methods

This prospective, observational, multicentric study was conducted at Policlinico Gemelli in Rome and Crohn's&Colitis Center at University of Miami. Consecutive IBD patients indicated for a new ADT between October 2023 and April 2024 were included. Each patient was screened for eligibility in actively recruiting RCTs at both centres, respectively 6 in Rome (4 for UC, 2 for CD) and 5 in Miami (3 for UC, 2 for CD).

Results

A total of 140 IBD patients (61 UC and 79 CD) were enrolled, 103 from the Italian cohort and 37 from the American cohort. Among UC patients, 14 (23.0%) were eligible for at least 1 clinical trial, while 45 (77.0%) were ineligible [p&lt;0.001]. Among CD patients, 5 (6.3%) were eligible for at least one clinical trial, while 74 (93.7%) were ineligible [p&lt;0.001]. For UC patients the most frequently failed criteria were MMS between 5-9 (45%), bowel urgency (45%), Mayo Endoscopic Score ≥ 2 (40%), the required washout period from the previous ADT (40%), the lack of response to 1 or more ADTs (39%) and absence of topical 5-ASA or steroid in the past 4 weeks (46%). For CD patients, the CDAI score of 220–450 was the most unmet criterion (85%), followed by "very soft or liquid SF≥ 4" (50%), washout periods (22%), SES-CD≥6 (21%) and CD-related complications (13%).

Conclusion

Most real-life IBD patients, especially CD, are ineligible for RCTs, primarily due to mild clinical disease activity or the need for ongoing treatments. Notably, real-life CD patients often initiate a new ADT due to radiological evidence of disease activity, complications or to prevent post-operative recurrence, while UC patients initiate ADT also when corticodipendent even with no or mild disease activity. Future RCTs should aim to include a broader range of patients’ subgroups to make their findings directly applicable to clinical practice.

References

1.Sands BE, Reinisch W, Schölmerich J, Bemelman W, Danese S, Mary JY, Rubin D, Colombel JF, Peyrin-Biroulet L, Dotan I, Abreu MT, Dignass A; International Organization for the Study of IBD. STRIDE-II: An Update on the Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE) Initiative of the International Organization for the Study of IBD (IOIBD): Determining Therapeutic Goals for Treat-to-Target strategies in IBD. Gastroenterology. 2021 Apr;160(5):1570-1583. doi: 10.1053/j.gastro.2020.12.031. Epu