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Retrospective Analysis of Efficacy and Safety of Tocilizumab Treatment in Patients with Severe Systemic-Onset Juvenile Idiopathic Arthritis Followed for 12 Months

DOI: 10.1155/2013/548312

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Abstract:

The results of the retrospective study evaluating efficacy and safety of tocilizumab treatment in 75 patients with severe systemic-onset juvenile idiopathic arthritis refractory to standard immunosuppressive therapy are presented in the paper. Inactive disease was documented in 64% of patients after 6 months of treatment and in 73% of patients after 12 months. Adverse events manifested as mild and moderate infections as well as laboratory abnormalities: leukopenia, neutropenia, and elevated aminotransferase levels. 1. Introduction Systemic-onset juvenile idiopathic arthritis (sJIA) is characterized by the chronic course of arthritis, persisting systemic manifestations (fever, rash, hepatosplenomegaly, lymphadenopathy, and serositis), and by significant elevation of laboratory inflammatory markers (leukocyte count, platelet count, ESR, CRP, and ferritin) [1]. sJIA is the severest type of juvenile idiopathic arthritis (JIA): chronic polyarthritis (with or without systemic manifestations) relapses in half of the patients, bone and cartilage destruction of the joints progresses, and severe functional impairment develop with consistently increasing disability [2, 3]. Treatment of sJIA is a complex problem of pediatric rheumatology due to low efficacy of methotrexate [4] at this type of disease as well as due to development of severe adverse events caused by glucocorticoid therapy. Many clinical and laboratory manifestations of the disease in sJIA are caused by high level of IL6 both in blood serum and in synovial fluid [5–11]. Hyperproduction of IL6 is associated with development of such extra-articular manifestations as fever and thrombocytosis. IL6 stimulates production of acute-phase inflammatory proteins (C-reactive protein and amyloid A, haptoglobin, and fibrinogen) by hepatocytes and also competitively inhibits synthesis of albumin and transferrin. IL6 stimulates secretion of hepcidin by hepatocytes which reduces absorption of iron in the intestine, and it inhibits its release from macrophages causing iron deficiency in erythropoiesis and development of anemia. IL6 in increased concentrations blocks production of adrenocorticotropic hormone, cortisol, and growth hormone which results in fatigue, sleepiness, depression, cognitive impairments, and growth retardation in children with sJIA. Amyloidosis, a severe complication of this disease, is also associated with activity of this cytokine. Tumor necrosis factor α inhibitors (TNF-α), as a rule, are ineffective in sJIA [12, 13]. Inhibition of IL6 at this type of the disease is more promising. Tocilizumab

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