S1494 Cigarette Smoking as a Predictor of Adverse Clinical Outcomes in Biologic-Treated Crohn’s Disease: A Propensity Score-Matched Analysis

Introduction: Cigarette smoking is the most consistently identified environmental risk factor associated with Crohn’s disease (CD), contributing to increased disease activity, complications, and poorer treatment outcomes. However, the extent to which smoking influences clinical outcomes in patients with CD receiving biologic therapy remains incompletely understood. Methods: This was a large population-based retrospective cohort using data from the TriNetX platform. Adult patients (≥18 years) with a diagnosis of Crohn’s disease receiving biologic therapy between January 1, 2014, and December 31, 2022, were included. Patients with an active history of tobacco use were propensity score matched (1:1) to nonsmokers based on demographics, comorbidities, and medication history. The index date was defined as one day following biologic therapy initiation. The primary outcome was the first incidence of CD flare-up. Secondary outcomes included bowel obstruction, fistula formation, abscess development, and all-cause mortality. Data was analyzed in February 2025 using Cox proportional hazards models to estimate hazard ratios (HRs) with 95% confidence intervals (CIs). Results: A total of 58,800 patients with CD were identified, of whom 6,674 had a history of tobacco use. After matching, 6,629 patients were included in each group. The smoking group had a significantly higher risk of CD flare-up (HR 1.122; 95% CI, 1.067–1.181), bowel obstruction (HR 1.241; 95% CI, 1.126–1.367), fistula formation (HR 1.33; 95% CI, 1.205–1.468), and abscess development (HR 1.916; 95% CI, 1.598–2.298), compared with nonsmokers (all P < 0.0001). These associations remained consistent in sensitivity analyses. In secondary analysis comparing biologic classes, anti–tumor necrosis factor agents, anti-integrins, and IL-23 inhibitors were each associated with increased flare-up risk, whereas JAK inhibitors showed a non-significant trend toward reduced risk (HR 0.919; 95% CI, 0.536–1.574). Conclusion: Active smoking was significantly associated with an increased risk of adverse clinical outcomes in patients with Crohn’s disease receiving biologic therapy. These findings highlight the importance of smoking cessation as a key component of disease management and highlight the need for further research evaluating long-term treatment response and safety outcomes across different biologic classes in smokers vs nonsmokers.