Introduction: Clinical trials are the key to research in inflammatory bowel disease therapeutics. However, their external validity has been poorly evaluated, as have the outcomes in patients who do not meet the inclusion criteria.
Methods: This retrospective observational study at Miguel Servet University Hospital, Zaragoza, Spain, included all consecutive patients diagnosed with Crohn's disease or ulcerative colitis who initiated biologic treatments between January 2017 and December 2022. Eligibility was assessed against the criteria of pivotal randomized clinical trials (RCTs) for adalimumab, infliximab, golimumab, ustekinumab, or vedolizumab. Clinical effectiveness and safety were evaluated at 14-16 weeks and 54 weeks, with treatment persistence assessed using survival analysis. Effectiveness and persistence were assessed to analyze whether patient selection has an impact on different clinical outcomes.
Results: A total of 631 biologic treatments were initiated in 477 patients. Only 16.9% met the RCT criteria according to pivotal RCTs and 8% with newer RCTs. Disease-related criteria were the most frequently unmet (57.3%). Patients with ulcerative colitis were less likely to meet the criteria compared with patients with Crohn's disease (23% vs 4%, P < 0.001). No significant differences were observed in response rates, remission rates, adverse events, or drug discontinuation between eligible and noneligible patients. Survival analysis showed no differences in treatment persistence between both groups (hazard ratio 1.01, 95% confidence interval 0.73-1.38).
Discussion: Only a minority of real-world patients with inflammatory bowel disease would qualify for corresponding RCTs, questioning the external validity of these trials. However, real-world use of biologics demonstrated similar effectiveness and safety in eligible and noneligible patients, underscoring the importance of practical clinical judgement in therapeutic decisions.
Keywords: Crohn's disease; biological drug; inflammatory bowel disease; randomized clinical trial; ulcerative colitis.
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