How comparative studies can inform treatment decisions for Crohn's disease

As new therapies for the treatment of Crohn's disease (CD) are approved, there is an increasing need for evidence that clarifies their positioning and sequencing.

Comparative effectiveness research (CER) aims to inform physicians' decisions when they choose which intervention (drug or treatment strategy) to administer to their patients. Pragmatic head-to-head trials represent the best tools for CER, but only a few have been published in the IBD field. Network meta-analyses can point toward the superiority of one drug over another, but they do not reflect everyday clinical practice. Finally, real-world evidence complements that coming from head-to-head trials and network meta-analyses, assessing the real-life effectiveness of therapeutic interventions.

There is insufficient evidence to create a definitive therapeutic algorithm for CD, but some general considerations can be made. Anti-TNF-α agents seemingly represent the most 'sustainable' first-line choice, considering benefit-harm ratio and costs; vedolizumab, ustekinumab, and risankizumab may be considered as first-line choice when safety issues become prominent. In the event of pharmacodynamic failure, out-of-class swap is to be preferred - possibly with anti-IL23p19 as the best option, with unclear data regarding upadacitinib positioning; a second anti-TNF-α could be considered, as a second choice, after pharmacokinetic failure.