Background/Purpose: The association between anti-TNF therapy and increased rate of infection are widely documented in adults with rheumatoid arthritis. Findings in children with juvenile idiopathic arthritis (JIA) have been less consistent and limited by small sample size and restricted follow up times. Dutch and German national registers documented low rates of serious infection (SI) in etanercept (ETN) treated patients with JIA, although one analysis has suggested more frequent SIs when ETN was used in combination with methotrexate (MTX). The aims of this analysis were (1) to compare rates of serious infection in JIA patients treated with ETN vs. MTX and (2) to compare the rates between ETN-MTX combination and ETN monotherapy.

Methods: To 31/5/2013, 677 ETN and 182 biologic-naive MTX control patients had been recruited to the BSPAR Etanercept Cohort Study, a UK national register established in 2004 to monitor the safety and effectiveness of ETN in children with JIA. All patients were followed by regular hospital questionnaires. Serious infections were defined as any infection regarded as medically significant by the patient’s clinican. This on-drug analysis followed all patients until first SI, death, treatment discontinuation or last follow-up date, whichever came first. Cox proportional hazards models were used to compare rates of SI between cohorts. Adjustments were made for potential confounders including age, gender, co-morbidities, oral steroid use, disease duration, ILAR category (systemic versus non-systemic) and disease severity, using a propensity score stratified into deciles (PD). Missing baseline data were accounted for using multiple imputation.

Results: The ETN cohort were older (mean 10.6 v 7.8 years), with longer disease duration (4.6 v 1.2 years), and had a higher proportion of children with systemic arthritis (15% v 4%). Disease activity was similar between the cohorts. The mean duration of follow up was 2.4 years in the ETN cohort, and 2.6 years in the MTX cohort. A total of 120 first SI’s were reported (99 ETN, 21 MTX). Patients on ETN had higher rates of SI than controls (PD adjusted HR 2.03 (1.12, 3.65)). The risk of SI did not differ between patients receiving ETN as monotherapy and those receiving ETN in combination with MTX (PD adjusted HR 1.24 (95 % CI 0.83, 1.86)). (Table)

Conclusion: ETN therapy is associated with an increased risk of SI in JIA patients. This risk does not increase further for ETN-MTX patients compared to ETN monotherapy patients.

Table: Patient characteristics and incidence of serious infection.