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.

Table 2 Comparative context for biologic switch strategies after ustekinumab failure in Crohn’s disease

Parameter	Risankizumab	Vedolizumab	Anti-TNF
Ref.	Colwill et al[6], 2025	Bressler et al[14], 2021	Allez et al[15], 2010
Study design	Single-center retrospective	Multicenter retrospective	Various retrospective
Sample size (n)	51	78	Approximately 50-100 per cohort
Follow-up	9 months	12 months	6-12 months
Clinical remission rate	94.4% (34/36)	39% (at 12 months)	Approximately 20%-40% (variable)
Biomarker improvement (CRP/FCal)	Significant (P < 0.001)	Modest	Modest to significant
Key strengths	High remission rates; excellent safety profile in this cohort	Distinct gut-selective mechanism; well-established safety	Extensive clinical experience; potential for dose optimization
Key limitations	Single-center; no endoscopic data; potential for selection bias	Lower remission rates in this setting	Immunogenicity; potential for attenuated response in later lines of therapy

TNF: Tumor necrosis factor; CRP: C-reactive protein; FCal: Fecal calprotectin.