IFX Is Associated with Higher Rates of 2-Year Mucosal Healing in Biologic-Naïve CD Patients Compared to UST

Abstract

Background and objective: The selection of optimal first-line biologic therapy for treatment-naïve Crohn's disease (CD) patients continues to present a clinical dilemma. Existing evidence remains limited by its predominant focus on anti-TNF-exposed populations or reliance on clinical endpoints alone. Our investigation provides a comprehensive comparative effectiveness analysis of ustekinumab (UST) versus infliximab (IFX) as first-line therapies in biologic-naïve CD, incorporating advanced cross-sectional imaging characteristics and specifically evaluating differential rates of endoscopic mucosal healing (MH) across longitudinal follow-up.

Methods: This retrospective cohort study enrolled 210 biologic-naïve CD patients. Primary outcome was MH at 1, 1.5, and 2 years. Subgroup analyses were performed to explore potential treatment heterogeneity among different patient subgroups. Furthermore, logistic regression analyses were conducted to identify MH-related factors.

Results: While 1-year and 1.5-year MH rates were comparable (27.8%/33.3% UST vs 30%/35.5% IFX; P = 0.726/0.788 unadjusted, P = 0.056/0.401 adjusted), IFX demonstrated significantly higher 2-year MH rates (59.5% vs 38.9%; adjusted P = 0.028). Patients with baseline BWT of 4-6 mm derived particular benefit from IFX, showing greater likelihood of achieving MH at both 1 year (OR 8.57, 95% CI 2.08-35.32; P = 0.003) and 1.5 years (OR 6.22, 95% CI 1.21-31.94; P = 0.028). Limberg > 2 consistently predicted worse MH outcomes across all time points (1-year OR 0.03, P < 0.001; 1.5-year OR 0.08, P = 0.008; 2-year OR 0.13, P = 0.024). Sustained MH correlated with lower 1-year HBI scores, and SES-CD. Notably, IFX treatment showed a strong independent association with 2-year MH achievement (OR 18.45, P = 0.002). Safety profiles were similar overall (P = 0.079), though IFX showed increased infection-related hospitalizations (P = 0.033) and immune-mediated adverse events, particularly drug-induced lupus (P = 0.033).

Conclusion: UST and IFX showed comparable efficacy and safety, but IFX demonstrated superior MH at 2 years. Patients with baseline BWT of 4-6 mm may benefit more from IFX.

Keywords: Biologic-naïve; Crohn’s disease; Infliximab; Mucosal healing; Ustekinumab.