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) . 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  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
R. E. Petty, T. R. Southwood, P. Manners et al., “International League of Associations for Rheumatology classification of juvenile idiopathic arthritis: second revision, Edmonton, 2001,” The Journal of Rheumatology, vol. 31, no. 2, pp. 390–392, 2004.
C. Lomater, V. Gerloni, M. Gattinara, J. Mazzotti, R. Cimaz, and F. Fantini, “Systemic onset juvenile idiopathic arthritis: a retrospective study of 80 consecutive patients followed for 10 years,” The Journal of Rheumatology, vol. 27, no. 2, pp. 491–496, 2000.
P. Woo, T. R. Southwood, A. M. Prieur, et al., “Randomized, placebo-controlled, crossover trial of low-dose oral methotrexate in children with extended oligoarticular or systemic arthritis,” Arthritis & Rheumatism, vol. 43, pp. 1849–1857, 2000.
F. De Benedetti, M. Massa, P. Robbioni, A. Ravelli, G. R. Burgio, and A. Martini, “Correlation of serum interleukin-6 levels with joint involvement and thrombocytosis in systemic juvenile rheumatoid arthritis,” Arthritis and Rheumatism, vol. 34, no. 9, pp. 1158–1163, 1991.
F. De Benedetti, P. Pignatti, V. Gerloni et al., “Differences in synovial fluid cytokine levels between juvenile and adult rheumatoid arthritis,” The Journal of Rheumatology, vol. 24, no. 7, pp. 1403–1409, 1997.
F. De Benedetti, T. Alonzi, A. Moretta et al., “Interleukin 6 causes growth impairment in transgenic mice through a decrease in insulin-like growth factor-I. A model for stunted growth in children with chronic inflammation,” The Journal of Clinical Investigation, vol. 99, no. 4, pp. 643–650, 1997.
F. De Benedetti, N. Rucci, A. Del Fattore et al., “Impaired skeletal development in interleukin-6-transgenic mice: a model for the impact of chronic inflammation on the growing skeletal system,” Arthritis and Rheumatism, vol. 54, no. 11, pp. 3551–3563, 2006.
M. Cazzola, L. Ponchio, F. De Benedetti et al., “Defective iron supply for erythropoiesis and adequate endogenous erythropoietin production in the anemia associated with systemic-onset juvenile chronic arthritis,” Blood, vol. 87, no. 11, pp. 4824–4830, 1996.
M. M. Schoels, D. Van Der Heijde, F. C. Breedveld, et al., “Blocking the effects of interleukin-6 in rheumatoid arthritis and other inflammatory rheumatic diseases: systematic literature review and meta-analysis informing a consensus statement,” Annals of the Rheumatic Diseases, vol. 72, no. 4, pp. 583–589, 2013.
G. Horneff, F. D. De Bock, I. Foeldvari et al., “Safety and efficacy of combination of Etanercept and methotrexate compared to treatment with Etanercept only in patients with juvenile idiopathic arthritis (jia): preliminary data from the german JIA registry,” Annals of the Rheumatic Diseases, vol. 68, no. 4, pp. 519–525, 2009.
F. H. M. Prince, M. Twilt, R. ten Cate et al., “Long-term follow-up on effectiveness and safety of etanercept in juvenile idiopathic arthritis: The Dutch National Register,” Annals of the Rheumatic Diseases, vol. 68, no. 5, pp. 635–641, 2009.
S. Yokota, T. Imagawa, and T. Miyamae, “Safety and efficacy of up to three years of continuous tocilizumab therapy in children with systemic-onset juvenile idiopathic arthritis [SAT0536],” Annals of the Rheumatic Diseases, vol. 68, supplement 3, p. 715, 2009.
Y. Inaba, C. Aoki, and R. Ozawa, “Radiologic evaluation of large joints during tocilizumab treatment in children with systemic juvenile idiopathic arthritis [SAT0555],” Annals of the Rheumatic Diseases, vol. 68, supplement 3, p. 720, 2009.
S. Yokota, T. Imagawa, M. Mori et al., “Efficacy and safety of tocilizumab in patients with systemic-onset juvenile idiopathic arthritis: a randomised, double-blind, placebo-controlled, withdrawal phase III trial,” The Lancet, vol. 371, no. 9617, pp. 998–1006, 2008.
S. Yokota, T. Miyamae, T. Imagawa et al., “Therapeutic efficacy of humanized recombinant anti-interleukin-6 receptor antibody in children with systemic-onset juvenile idiopathic arthritis,” Arthritis and Rheumatism, vol. 52, no. 3, pp. 818–825, 2005.
U. Kaneko, T. Imagawa, and T. Kishi, “Discrepancy between progression of joint damage and improvement of systemic inflammation in patients with systemic-onset juvenile idiopathic arthritis treated with tocilizumab [SAT0548],” Annals of the Rheumatic Diseases, vol. 68, supplement 3, p. 719, 2009.
F. De Benedetti, H. I. Brunner, N. Ruperto, et al., “Randomized trial of tocilizumab in systemic Juvenile idiopathic arthritis,” The New England Journal of Medicine, vol. 367, no. 25, pp. 2385–2395, 2012.
S. Yokota, T. Tanaka, and T. Kishimot, “Efficacy, safety and tolerability of tocilizumab in patients with systemic juvenile idiopathic arthritis,” Therapeutic Advances in Musculoskeletal Disease, vol. 4, no. 6, pp. 387–397, 2012.
J. S. Smolen, M. M. Schoels, and N. Nishimoto, “Consensus statement on blocking the effects of interleukin-6 and in particular by interleukin-6 receptor inhibition in rheumatoid arthritis and other inflammatory conditions,” Annals of the Rheumatic Diseases, vol. 72, no. 4, pp. 482–492, 2013.
E. Alexeeva, R. Denisova, S. Valieva et al., “Safety and efficacy of tocilizumab treatment in children with systemic onset of juvenile idiopathic arthritis,” Pediatric Rheumatology, vol. 9, supplement 1, article P202, 2011.
C. A. Wallace, E. H. Giannini, B. Huang, et al., “American College of Rheumatology provisional criteria for defining clinical inactive disease in select categories of juvenile idiopathic arthritis,” Arthritis Care & Research, vol. 63, no. 7, pp. 929–936, 2011.
M. H. Schiff, J. M. Kremer, A. Jahreis, E. Vernon, J. D. Isaacs, and R. F. van Vollenhoven, “Integrated safety in tocilizumab clinical trials,” Arthritis Research and Therapy, vol. 13, no. 5, article R141, 2011.
S. Davi, B. Lattanzi, S. Rosina, et al., “Sensitivity and specificity of current diagnostic guidelines in children with macrophage activation syndrome complicating systemic juvenile idiopathic arthritis,” Pediatric Rheumatology, vol. 9, supplement 1, article P101, 2011.