Increased incidence of inflammatory bowel disease on etanercept in juvenile idiopathic arthritis regardless of concomitant methotrexate use

Abstract

Objectives: To describe risk factors for inflammatory bowel disease (IBD) development in a cohort of children with juvenile idiopathic arthritis (JIA). Methods: JIA patients who developed IBD were identified from the international Pharmachild register. Characteristics were compared between IBD and non-IBD patients and predictors of IBD were determined using multivariable logistic regression analysis. Incidence rates of IBD events on different disease-modifying anti-rheumatic drugs (DMARDs) were calculated, differences between therapies were expressed as relative risks (RR). Results: Out of 8,942 patients, 48 (0.05%) developed IBD. These were more often male (47.9% vs 32.0%) and HLA-B27 positive (38.2% vs 21.0%) and older at JIA onset (median 8.94 vs 5.33 years) than patients without IBD development. They also had more often a family history of autoimmune disease (42.6% vs 24.4%) and enthesitis-related arthritis (ERA) (39.6% vs 10.8%). The strongest predictors of IBD on multivariable analysis were ERA (OR: 3.68, 95% CI: 1.41-9.40) and a family history of autoimmune disease (OR: 2.27, 95% CI: 1.12-4.54). Compared with methotrexate monotherapy, the incidence of IBD on etanercept monotherapy (RR: 7.69, 95% CI: 1.99-29.74), etanercept with methotrexate (RR: 5.70, 95% CI: 1.42-22.77) and infliximab (RR: 7.61, 95% CI: 1.27-45.57) therapy was significantly higher. Incidence on adalimumab was not significantly different (RR: 1.45, 95% CI: 0.15-13.89). Conclusion: IBD in JIA was associated with ERA and a family history of autoimmune disease. An increased IBD incidence was observed for etanercept therapy regardless of concomitant methotrexate use.