Biologic Therapies in Juvenile Idiopathic Arthritis

Objective: To investigate the single-center experience of the efficacy and safety profile of biologic therapies in patients with juvenile idiopathic arthritis (JIA) and identify risk factors associated with adverse events (AEs).Methods: The medical charts of children with JIA diagnosed between January 2010 and December 2021 were reviewed retrospectively, and patients treated with biological agents were included in the study. Demographic data, clinical features, laboratory results, treatments used, and AEs during the treatment period were collected.Results: From the total JIA cohort (n=814), 237 patients who received biologic therapy for at least 3 months were enrolled in the study. The most frequent subtype was persistent oligoarticular JIA (45.1%) and the most frequently used biologic drug was etanercept (n=118), followed by adalimumab (n=64), tocilizumab (n=31), anti-interleukin-1 (anti-IL-1) agents (n=12; 7 anakinra and 5 canakinumab), infliximab (n=6), abatacept (n=3), secukinumab (n=2) and tofacitinib (n=1). One hundred sixty-four (69.2%) patients received disease-modifying antirheumatic drugs (DMARDs) concomitantly, 10.5% received DMARDs plus corticosteroids and 2.1% received only corticosteroids. The median [interquartile range (IQR)] age and median age at initiation of the biologics were 14.4 (10.7-18) years and 10.9 (6.6-14.5) years, respectively. The median (IQR) followup period was 3.9 (2-6.3) years. On biologic therapy, the median (IQR) JADAS-71 decreased from 13 (11-19) at baseline to 0 (0-2) after median 22 (10-40) months of treatment (p<0.001). The most frequent AE was local injection site reactions with biologics administered subcutaneously (n=8), followed by upper respiratory tract infections (n=4) and diffuse erythematous skin rashes (n=4). Serious AEs were observed in 11 (4.6%) patients. To compare the frequency of AEs, patients were divided into three groups according to the biologics administered, as follows: Group 1: Tumor necrosis factor inhibitors, group 2: anti-IL-1 agents, group 3: anti-IL-6 agent. The frequency of AEs was significantly higher in JIA patients on anti-IL-1 therapy than in the other two groups (58.3% vs. 29% and 8.5%, p<0.001).Conclusion: Biological agents are used with increasing frequency in children with JIA, and their off-label use is quite common. Although these agents are considerably effective and quite safe, AEs should not be underestimated. While planning the management of patients with refractory JIA, careful interpretation of benefit-risk balance for every individual patient seems to be reasonable and required.