Real-world effectiveness of guselkumab for induction of remission in Crohn’s disease: a prospective multicenter cohort study with propensity score–matched comparison to risankizumab

Background
No head-to-head trials compare selective interleukin-23 inhibitors in Crohn’s disease (CD), leaving clinicians without direct evidence to guide treatment selection. We aimed to evaluate the real-world induction effectiveness of guselkumab in CD and perform propensity score–matched (PSM) comparisons against risankizumab.

Methods
This prospective multicenter study included adults with moderate-to-severe CD initiating guselkumab in the United Arab Emirates. The primary outcome was clinical remission at Week 12 (Harvey-Bradshaw Index <5). Full propensity score matching between guselkumab and risankizumab cohorts controlled for 12 covariates, including disease phenotype, baseline endoscopic and biochemical activity, surgical history, and current smoking status.

Results
Fifty-one guselkumab and 60 risankizumab patients were included. In the guselkumab cohort, 71% were advanced therapy-exposed with a median of 2 prior advanced therapies. At Week 12, clinical remission was achieved in 51% (26/51) and clinical response in 86% (44/51). Median C-reactive protein (CRP) decreased from 8.5 to 3.0 mg/L (P = .002) and fecal calprotectin from 216 to 80 μg/g (P < .001). Effectiveness was consistent regardless of prior treatment history. On univariable analysis, higher baseline HBI (OR 0.77, P = .011), SES-CD (OR 0.87, P = .049), and CRP (OR 0.94, P = .019) were associated with lower remission likelihood. Maintenance dosing was 100 mg Q8W in 73% and 200 mg Q4W in 27%. PSM analysis demonstrated comparable clinical remission (51% vs 50%, P > 0.9) and clinical response (86% vs 87%, P = .87) between guselkumab and risankizumab, with no significant between-group biomarker differences.

Conclusions
Guselkumab demonstrated robust real-world induction effectiveness comparable to risankizumab across clinical and biochemical outcomes. These findings warrant confirmation in larger, longer-term comparative studies with endoscopic endpoints.