Real-World IBD Patients Rarely Meet Biologic Clinical Trial Eligibility Criteria

July 21, 2026

Issue 14

Clinical Question

Do patients treated with biologics in clinical practice meet pivotal RCT eligibility criteria, and does eligibility status affect outcomes?

Editor’s Bottom Line

The majority of patients treated with advanced therapies for IBD would not have been eligible for the clinical trials that informed their use. Clinicians should be mindful of this when deciding on therapy and counselling patients.

Reference

Casas Deza D, Larrubia Domínguez C, Pascual Oliver A, et al. Patients Included in Clinical Trials of Biological Drugs for Inflammatory Bowel Disease Do Not Represent the Real-World Population. Am J Gastroenterol. 2026;121(6):1424-1434. https://doi.org/10.14309/ajg.0000000000003670

Synopsis

This single-centre retrospective study from a tertiary IBD unit in Zaragoza, Spain, included 477 consecutive patients with Crohn’s disease (CD) or ulcerative colitis (UC) who initiated treatment with adalimumab, infliximab, golimumab, ustekinumab or vedolizumab between January 2017 and December 2022. This study accounted for 631 total treatment initiations, as some patients started more than one biologic during the study period. Seventy-five percent of patients had CD and the median follow-up was 30 months. Eligibility for each treatment was assessed against the inclusion/exclusion criteria of pivotal randomized controlled trials (RCTs). Additional trials, which tended to have stricter criteria than those for initial pivotal trials, were included for adalimumab and infliximab. Clinical effectiveness was evaluated at 14 –16 weeks and at 54 weeks. Treatment persistence was assessed by Kaplan-Meier survival analysis.

Results showed that only 16.9% of treatment initiations met pivotal RCT criteria for the agents they were starting, falling further to 8.9% against subsequent trial criteria for adalimumab and infliximab. Disease-severity thresholds were the most frequently unmet criterion (57%). There was substantial drug-level variability: against pivotal trial criteria, infliximab had the lowest eligibility rate (0.8%), driven mainly by prior biologic use (excluding 83% of patients) and age restrictions, while adalimumab had the highest eligibility rate (29%). Eligibility also differed by disease type, and in opposite directions depending on the trial era used: against pivotal RCT criteria, UC patients were less likely to be eligible than CD patients (12.7% vs. 18.3%), whereas against newer trial criteria this relationship reversed, with UC patients more frequently eligible than CD patients (23.4% vs. 4%).

Despite the low eligibility rate, eligibility did not predict outcomes: response rates, remission rates, adverse events and drug discontinuation did not differ between eligible and non-eligible patients at weeks 14 and 54.. Treatment persistence was equivalent on survival analysis (Hazard Ratio [HR]: 1.01; 95% Confidence Interval [CI], 0.73–1.38) and confirmed on multivariable Cox regression (HR: 1.32; 95% CI, 0.91–1.90). At the drug level, however, the picture was more nuanced: ustekinumab showed greater persistence in eligible patients, while vedolizumab showed greater persistence in non-eligible patients. A higher week-54 remission rate was seen in patients who met eligibility criteria for newer trials than those who did not (59% vs. 49%; p=0.019).

Details

Study Design: Single-centre retrospective observational study
Funding: Instituto de Salud Carlos III, Madrid, Spain
Allocation: Not applicable
Setting: Single centre
Level of Evidence: 2b