Real-world comparative effectiveness and persistence of ustekinumab versus vedolizumab across cohort mean age in Crohn’s disease: A systematic review and meta-analysis with meta-regression

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Background Selecting biologic therapy for older patients with inflammatory bowel disease is challenging given limited age-specific data. Objectives We examined whether cohort mean age is associated with the comparative effectiveness and persistence of ustekinumab (UST) versus vedolizumab (VDZ). Design Systematic review and meta-analysis with meta-regression of real-world comparative studies. Data Sources and Methods We searched MEDLINE, Embase, Cochrane CENTRAL, and KoreaMed from inception to January 9, 2026 for real-world comparative studies reporting adjusted estimates, and synthesized 48–52 week effectiveness and persistence separately using inverse-variance random-effects models, exploring age effects by subgroup analysis and meta-regression. Results Seventeen publications comprising 18 cohorts were included, with Crohn’s disease (CD) predominating and ulcerative colitis data limited. Pooled effectiveness favored UST in CD (adjusted odds ratio 1.70, 95% confidence interval 1.13–2.56) but not in the stratum with a cohort mean age of ≥60 years (0.91, 0.32–2.56), with a significant between-subgroup difference (P = 0.0038). Cohort mean age was not a significant moderator of effectiveness in meta-regression (slope −0.0393, P = 0.093; e β 0.96 per year, 95% CI 0.92–1.01). Persistence favored UST (adjusted hazard ratio 1.59, 1.21–2.10) with no age association (P = 0.903), and biologic-naive proportion was not a significant moderator. Conclusion In CD, UST was favored over VDZ for both effectiveness and persistence, and its effectiveness advantage appeared to attenuate with increasing cohort mean age. Because these are study-level data, this age-related pattern warrants confirmation through patient-level analyses and dedicated studies in older adults, in whom direct comparative evidence remains limited.