Levels of antibodies to adalimumab in children with juvenile idiopathic arthritis at different stages of treatment

Abstract

Background. Juvenile idiopathic arthritis (JIA) is one of the most common rheumatological diseases of childhood. The central place in the problem of JIA belongs to the question of treatment the timeliness and adequacy of which determine the disease prognosis and, in fact, the entire future of the child. Immunobiological therapy can cause stable clinical and laboratory remission, as well as stop the further progression of structural changes, affecting the pathogenetic link of idiopathic arthritis. But the lack of response to therapy or a decrease in its effectiveness remains a fairly common problem and, in many cases, can be caused by the immunogenicity of immunobiological drugs, especially in case of treatment with tumor necrosis factor inhibitors. Aim of the work: to study the level of antibodies to adalimumab in children with juvenile idiopathic arthritis at different stages of treatment for analysis of immunogenicity. Materials and methods. The concentration of antibodies to adalimumab in 80 serum samples from patients with JIA was studied and evaluated, treatment effectiveness and adverse events were analyzed in 56 patients with JIA at different stages of therapy. Two groups were identified. The first one included 24 patients who had at least a 6-month break in adalimumab administration for non-medical reasons during which treatment was continued with methotrexate with periodic intra-articular injection of glucocorticoids. The level of antibodies to adalimumab was evaluated before the break and 1 month after the reinitiation of adalimumab administration. The second group consisted of 32 children who continued adalimumab without a break during treatment. Disease activity was measured using JADAS-27. Antibodies to adalimumab were detected by enzyme-linked immunosorbent assay. Results. During the examination, an elevated level of antibodies to adalimumab was detected in 10 of 24 serum samples (42 %) before non-medical withdrawal in group I. Among the results of group II, elevated levels of antibodies to adalimumab were found in 12 samples, which was 38 %. The correlation analysis revealed direct statistically significant relationships of moderate strength between the level of antibodies to adalimumab and the indicator of inflammatory activity on JADAS-27 (Spearman’s r = 0.39, p < 0.05), as well as between the level of antibodies and disease duration (Spearman’s r = 0.32, p < 0.05). Conclusions. Monitoring serum antibodies to adalimumab is informative for the correct interpretation of treatment effectiveness and the course of the disease with immunobiological treatment, as it may improve understanding of the clinical consequences of continued therapy, help prevent adalimumab immunogenicity, develop follow-up strategies and, as a result, can affect a long-term outcome of treatment for JIA.

Keywords

• juvenile idiopathic arthritis
• adalimumab
• antibodies to adalimumab
• immunogenicity
• tnf-α inhibitors