Biosimilars in inflammatory bowel disease: from initial uncertainty to clinical normalization.

Abstract

Biosimilars have become an integral part of the treatment of inflammatory bowel disease (IBD), evolving from initial uncertainty regarding indication extrapolation and non-medical switching to widespread clinical acceptance. Early concerns focused mainly on the absence of disease-specific evidence and the potential impact of switching on effectiveness, safety, and immunogenicity. Over the past decade, however, extensive real-world evidence and randomized data have consistently supported the use of infliximab and adalimumab biosimilars in both biologic-naïve patients and patients switched from originator products. Recent systematic reviews and meta-analyses further reinforce these findings, showing preserved clinical remission, treatment persistence, inflammatory biomarkers, and immunogenicity after switching. The biosimilar landscape is now expanding to newer therapeutic targets, including ustekinumab, while biosimilar-to-biosimilar and multiple switching is becoming increasingly relevant in routine practice. Nevertheless, scientific interchangeability should not be equated to automatic substitution. Switching decisions should remain clinically supervised and involve gastroenterologists within a multidisciplinary framework, taking into account disease activity, previous response, safety, immunogenicity, and patient preferences. Appropriate communication is also essential to minimize a potential nocebo effect and to avoid unnecessary discontinuation. Biosimilars should therefore be considered fully established biological therapies rather than lower-tier alternatives to originator drugs. Future research should focus less on re-confirming single-switch equivalence and more on unresolved questions, including long-term outcomes after multiple switching, biosimilars of newer therapeutic targets, patient-reported outcomes, treatment persistence, and comparative pharmacoeconomic impact across healthcare systems.