Real-World Effectiveness of Guselkumab for Induction of Remission in Crohn’s Disease: A Prospective Multicentre 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 real-world induction effectiveness of guselkumab in CD and perform propensity score-matched (PSM) comparisons against risankizumab. Methods This prospective multicentre 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 CRP decreased from 8.5 to 3.0 mg/L (p = 0.002) and faecal calprotectin from 216 to 80 ug/g (p < 0.001). Effectiveness was consistent regardless of prior treatment history. On univariable analysis, higher baseline HBI (OR 0.77, p = 0.011), SES-CD (OR 0.87, p = 0.049), and CRP (OR 0.94, p = 0.019) 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 = 0.87) 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.