Introduction

Treatment goals in inflammatory bowel disease (IBD) have evolved beyond symptom control to include mucosal healing, prevention of disease-related complications, improvement of health-related quality of life, and reduction of long-term disability, as outlined by the STRIDE II initiative¹. Despite significant progress in the development of advanced therapies (ADTs), up to 50% of IBD patients fail to respond to currently available treatments, underscoring the urgent need for new therapies, which are investigated in randomized clinical trials (RCTs). However, stringent eligibility criteria in RCTs limit the inclusion of real-world IBD patients, potentially compromising the generalizability of trial findings to daily clinical practice.

Aims & Methods

The aim of this study was to evaluate the proportion of real-life IBD patients who would be eligible for ongoing RCTs and to assess the representativeness of this population. Moreover, we aimed to identify the most frequently unmet eligibility criteria leading to patient exclusion and to characterize the clinical profiles that differentiate eligible from ineligible patients.
This prospective, observational, multicenter study was conducted between October 2023 and October 2024 at 2 tertiary IBD referral centers: the Fondazione Policlinico Universitario “A. Gemelli” in Rome, Italy, and the Crohn’s & Colitis Center at the University of Miami, USA. Consecutive patients with IBD indicated for a new ADT were enrolled. Each patient was systematically screened for inclusion and exclusion criteria across all actively recruiting phase 2b and 3 RCTs available at each center at the time of evaluation (6 RCTs in Rome: 4 UC and 2 CD; 5 RCTs in Miami: 3 UC and 2 CD).

Results

A total of 166 IBD patients (69 UC and 97 CD) were enrolled, with 129 patients from the Italian cohort and 37 from the American cohort. Among UC patients, only 16 (23.2%) met the eligibility criteria for at least 1 RCT, whereas 53 (76.8%) were deemed ineligible (p<0.001). In the CD group, just 10 patients (10.3%) were eligible for at least 1 RCT, compared to 87 (89.7%) who were not (p<0.001). The most common reasons for ineligibility among UC patients included: Modified Mayo score not within the required range of 5–9 (50.7%), absence of bowel urgency (63.8%), Mayo Endoscopic Subscore <2 (39.1%), failure to comply with ADT washout requirements (56.5%), insufficient number of prior ADT failures (39.0%), and recent use of topical 5-ASA or steroids within 4 weeks prior to screening (62.3%).
In CD patients, the most frequently unmet criterion was a CDAI between 220 and 450 (92.8%), followed by insufficiently liquid stool frequency (≥4 very soft or liquid stools/day; 75.3%), SES-CD<6 (39.2%), and the presence of CD-related complications such as strictures or fistulas (13.1%).

Conclusion

The majority of real-life IBD patients, particularly those with CD, are ineligible for participation in current RCTs—primarily due to relatively mild disease activity or ongoing need for concomitant therapies that are not permitted by trial protocols. Importantly, many real-world CD patients initiate new ADTs based on radiologic signs of disease activity, the presence of disease complications, or as prophylaxis for post-surgical recurrence, rather than clinical activity scores alone. Similarly, UC patients may require ADTs even in the context of corticosteroid dependence and low-grade disease activity. These findings underscore the need to revisit and broaden eligibility criteria in future RCTs to ensure greater external validity and alignment with the heterogeneity of real-life IBD population.

References

1. Turner D, Ricciuto A, Lewis A, D'Amico F, Dhaliwal J, Griffiths AM, Bettenworth D, Sandborn WJ, 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. Epub 2021 Feb 19. PMID: 33359090.

Introduction

Deep remission in complex perianal fistulizing Crohn’s disease (PFCD) is defined by both clinical and radiological remission. As the ultimate therapeutic goal for this condition, deep remission requires thorough assessment. MRI is the gold standard for evaluating complex perianal involvement.

Aims & Methods

Our aim was to identify baseline MRI factors linked to deep remission in PFCD and assess its impact on clinical outcomes. All patients with complex PFCD treated with anti-TNF-α agents at the gastroenterology department underwent baseline MRI and clinical evaluation. Radiological assessment included the number and type of fistula tracts (per Parks classification), presence/size of pelvic collections, horseshoe tracts (encircling more than 75% of the anal circumference), and rectal wall thickening. The Van Assche score was calculated. Follow-up MRIs were obtained only after clinical remission to assess radiological remission.

Results

Out of 105 patients, 80 were included in the study (male-to-female ratio: 1.33), with a mean age of 32.35 years. On average, patients had 1.7 fistula tracts (range: 1–6), with trans-sphincteric fistulas accounting for 65% of cases. Specific subtypes included ano-vulvar tracts in 8 women (9.5%), rectovaginal in 5 patients (6%), and anorectal tracts extending to the scrotum in 2 men (2.4%). Pelvic collections were present in 14 individuals (16.7%), averaging 23.8 mm in size. Horseshoe-shaped tracts were identified in 19 patients (22.6%), and rectal wall thickening greater than 3 mm was seen in 49 (58.3%). The mean Van Assche MRI score was 14.9. All patients underwent seton placement. The majority (88.1%) received infliximab, while the remainder were treated with adalimumab. Clinical remission was achieved after a mean of 5.8 months. Radiological remission occurred in 24 patients (28.6%). Presence of horseshoe tracts (p=0.013) and Van Assche scores more than 14 (p=0.027) were significantly associated with failure to reach radiological remission. These factors were confirmed as independent predictors by multivariate analysis. Among those who initially achieved radiological remission, 13 experienced recurrence during an average follow-up of 65.8 months. Radiological remission was associated with improved outcomes: recurrence-free survival rates were 81.3% at 1 year, 62.7% at 3 years, and 50.1% at 5 years, compared to 62.2%, 35.8%, and 23.2%, respectively, in patients with clinical remission but without radiological remission.

Conclusion

Deep remission was achieved in about one-third of PFCD patients following clinical remission. Horseshoe fistulas and Van Assche score more than 14 predict failure to reach this goal, correlating with worse long-term outcomes. These findings support the Top-Class classification designating such cases as unsuitable for curative repair, emphasizing symptom control instead.