Severe Influenza-Related Outcomes in Patients with Inflammatory Bowel Disease on Immunosuppressive Therapy: A Propensity-Matched Cohort Analysis

BACKGROUND: Patients with active inflammatory bowel disease (IBD) often require immunosuppressive therapy to achieve and maintain remission; however, the impact of these medications on influenza risk and the severity of influenza-related complications remains inadequately characterized. METHODS: Using the TriNetX U.S. Analytics Network, adults (≥ 18 years) with Crohn's disease or ulcerative colitis during the 2022-2023 influenza season were identified. Patients were stratified by disease activity into two cohorts: (1) active IBD, defined by elevated inflammatory markers, initiation of corticosteroids or a new biologic or small-molecule agent, or documented IBD-related symptoms or complications within the prior six months; and (2) inactive IBD, defined by the absence of these features and no recent immunosuppressive therapy. Propensity score matching (1:1) was used to balance baseline characteristics, and Cox proportional hazards models were applied to estimate hazard ratios for influenza-related outcomes. RESULTS: After propensity score matching, each group had 22,784 patients. The incidence of influenza diagnosis was significantly higher in the active IBD group (HR 1.41; 95% CI 1.30-1.52). Hospitalization rates were also increased (HR 2.05; 95% CI 1.89-2.23), as were influenza-related complications (HR 1.36; 95% CI 1.23-1.51). ICU admissions (HR 1.51; 95% CI 1.33-1.72) and mechanical ventilation (HR 1.68; 95% CI 1.32-2.13) were both more frequent in the active IBD group. Use of antiviral medications was higher among patients with active IBD (HR 1.60; 95% CI 1.22-2.10), and overall mortality was modestly increased (HR 1.17; 95% CI 1.02-1.35). Subgroup analysis revealed the highest risk among patients on corticosteroids, followed by JAK inhibitors and anti-IL-23 agents. CONCLUSION: Patients with active IBD had more severe influenza-related outcomes compared with those with inactive IBD. Improving vaccine uptake and prompt evaluation of upper respiratory symptoms during influenza seasons are key to reducing influenza-related risks in immunosuppressed patients with IBD.