Background Knowledge of adverse drug events (ADEs) caused by biologic agents used in paediatric populations is limited (1,2). Furthermore, the majority of these drugs are administrated off-label.
Objectives To analyze the safety profiles of biologic agents and characteristics of ADEs in a clinical sample of paediatric patients with JIA and to identify potential risk factors associated with ADEs.
Methods A retrospective, longitudinal, study of paediatric patients <18 years diagnosed with JIA at the paediatric department of Copenhagen University Hospital.
Inclusion: treatment with ≥1 biologic drug from January 1. 2009, through December 31. 2012.
ADEs and off-label use were identified by review of medical records and classified according to the European Medical Agency guidelines.
Demographic data were assessed using descriptive statistics. Survival analysis was used to analyze time to an ADE. Multivariable logistic regression models adjusted for age, gender and disease subtype were used to investigate risk factors associated with ADEs. Statistical significance was set to p<0.05.
Results 182 patients were included, 71% females. Age ranged from 1-18 years (mean 12.3 years). The 182 patients had a total of 2563 drug prescriptions for etanercept (33%), infliximab (31%), adalimumab (17%), golimumab (10%), abatacept (6%) and tocilizumab (3%). 71% of treatments were classified as off-label. In total, 519 ADEs were observed in 80.8% of the patients. Time to an ADE did not differ with respect to type of drug. The three most common drug reactions were neutropenia, infections and elevated ALAT. We found a statistically significant risk of neutropenia among those in treatment with eternacept and tocilizumab compared to infliximab, adalimumab, golimumab, and abertacept. In contrast, we found a decreased risk of neutropenia with golimumab, and abatacept, compared to the remaining drugs. Adalimumab was the only drug associated with a significant risk of ALAT increase. There was no difference in risk of infection between drugs. The risk of either neutropenia, ALAT increase or an infection was not associated with age. However, the overall risk of any drug event independent of drug used decreased with age. Finally, we did not find any association between gender and risk of ADEs.
Conclusions This study found a statistically significant difference in safety profiles between biologic agents used in the treatment of JIA. Additionally, ADEs are frequent in this population of paediatric patients. However, gender was not associated with an increased risk of ADEs and risk of ADE declined with age. These results need to be evaluated in independent cohorts.
Otten MH, Prince FH, Anink J, Ten CR, Hoppenreijs EP, Armbrust W, et al. Effectiveness and safety of a second and third biological agent after failing etanercept in juvenile idiopathic arthritis: results from the Dutch National ABC Register. Ann Rheum Dis 2013 May;72(5):721-7
Horneff G. Pediatric rheumatic disease: Biologic therapy and risk of infection in children with JIA. Nat Rev Rheumatol 2012 Sep;8(9):504-5
Disclosure of Interest None declared