Effects of antirheumatic treatment with tocilizumab on longitudinal growth in children with juvenile idiopathic arthritis

Abstract

Background: Inflammation and glucocorticoid therapy are major factors in the growth retardation seen in children with severe systemic juvenile idiopathic arthritis (JIA). Objective and hypotheses: The objective of the this study was to evaluate effects of biologic treatment with recombinant humanised monoclonal antibody that acts as IL-6R antagonist (tocilizumab) on longitudinal growth. Methods: Nineteen patients with severe systemic JIA was included into the study (8 boys and 11 girls). The mean age at first visit was 6.8 +/- 2.4 years, and disease duration 4 (2,2;6) years. All patients had stage 1 of sexual development by Tanner scale and before therapy with tocilizumab had standard antirheumatic therapy. Anthropometric parameters were estimated one year before tocilizumab treatment, at the day of first infusion and in one year after tocilizumab treatment was started. Tocilizumab was administered intravenously once every 2 or 4 weeks at a dose of 8-10 mg/kg of body weight. In all patients who received corticosteroids before tocilizumab treatment dose of these drugs was reduced, but not in one case it was completely abolished. Treatment efficacy was assessed according to criteria ACR pedi scale. Results: The mean height SDS one year before treatment was -2.38 +/-1.43 and height velocity SDS was -4.24 +/-1.18. On the standard antirheumatic therapy during the first year of monitoring in all patients was noted deterioration in growth, and by the day of 1st tocilizumab infusion height SDS was -2.64+/-1.94 and height velocity -4.55 +/-1.49 (p < 0.001). After one year of treatment clinical response ACR 50 to the treatment was obtained in all patients included in this study. The mean height SDS was -2.27 +/-1.85 and height velocity SDS +2.51 +/-1.98 (p < 0.001) Conclusions: An intensified biologic treatment with tocilizumab has a beneficial effect on growth in children with JIA. This effect might be related to the inhibitory effect of proinflammatory cytokines, especially Il-6, on the synthesis of IGF-1 and IGF-BP-3.