BACKGROUND AND AIMS: We conducted this nationwide study to evaluate the association between peripheral blood eosinophilia (PBE) and long-term outcomes in children and adults with inflammatory bowel diseases (IBDs). METHODS: Data from the Epidemiology Group of the Israeli IBD Research Nucleus (epi-IIRN) cohort, a validated population-based IBD database, included patients diagnosed between 2005 and 2020, who had an eosinophil count recorded at diagnosis, and non-IBD controls. PBE was defined as an eosinophil count of >
0.5 × 109/L. Severe disease course was defined as corticosteroid dependency, use of ≥2 biologics from different classes, or surgery. Time-to-outcomes, including severe disease course, was determined by Cox proportional hazard models. RESULTS: This study included 28 133 patients (15 943 Crohn's disease [CD] and 12 190 ulcerative colitis [UC]) and 28 724 non-IBD controls. The prevalence of PBE was 13% in the IBD group and 5% in the control group (p <
0.001). PBE was more prevalent in UC (16.1%) compared to CD (10.6%, odds ratio [OR] = 1.52, 95% confidence interval [CI], 1.42-1.63
p <
0.001) and in pediatric-onset (23.5%) compared to adult-onset (11%) IBD (OR = 2.14, 95% CI, 1.97-2.31
p <
0.001). In a multivariate analysis, PBE was a predictor of severe disease course in IBD (hazard ratio [HR] = 1.49, 95% CI, 1.38-1.62, p <
0.001). PBE also predicted time-to-hospitalization (HR = 1.24, 95% CI, 1.19-1.30), use of corticosteroids (HR = 1.32, 95% CI, 1.28-1.36), corticosteroid dependency (HR = 1.37, 95% CI, 1.31-1.43), and need for biologics (HR = 1.27, 95% CI, 1.21-1.33). CONCLUSIONS: In this largest nationwide study, PBE predicted severe IBD course. These findings support the use of PBE as a marker of adverse outcomes of IBD and as a potential target for future therapies.