Risankizumab redefines Crohn’s treatment after ustekinumab failure

Table 1 Comparison of traditional vs emerging paradigms in biologic sequencing for Crohn’s disease

Feature	Traditional paradigm (cross-class)	Emerging paradigm (intra-class/pathway)
Rationale	Avoid shared mechanisms of failure by targeting a completely different pathway	Leverage deeper, more specific inhibition within a known pathogenic pathway
Example sequence	Anti-TNF → vedolizumab (anti-integrin) → ustekinumab (anti-IL-12/23)	Ustekinumab (anti-IL-12/23 p40) → risankizumab (anti-IL-23 p19)
Key driver	Drug class	Mechanism of action and pathway specificity
Supporting evidence	Extrapolated from trials in biologic-naïve patients; real-world cohort studies	Direct real-world evidence from Colwill et al[6] and others[13] showing high efficacy
Advantage	Theoretically avoids class-specific failure mechanisms	Higher efficacy can be achieved by targeting the core pathway with greater specificity

TNF: Tumor necrosis factor; IL: Interleukin.