Drs Li and Geskey have disclosed no financial relationship relevant to this commentary. This commentary does not contain a discussion of an unapproved/investigative use of a commercial product/device.Investigators from multiple pediatric rheumatology centers conducted an international double-blind, placebo-controlled randomized clinical trial of tocilizumab (an anti-interleukin- 6 receptor antibody) for the treatment of systemic juvenile idiopathic arthritis (JIA).1 Patients were evaluated for response or flare according to JIA American College of Rheumatology (ACR) criteria, in which a JIA ACR30 response means the patient had 30% or greater improvement in at least 3 of 6 parameters (number of joints with active arthritis, number of joints with limited range of motion, physician assessment of disease activity, patient assessment of well-being, physical function, and erythrocyte sedimentation rate), no more than 1 parameter worsening by 30%, and an absence of fever.At the end of 12 weeks significantly greater improvement was found in patients treated with tocilizumab, with 85% achieving JIA ACR30, 71% achieving JIA ACR70, and 37% achieving JIA ACR90 compared to 24%, 8%, and 5%, respectively, for the placebo arm (P < .001 for all). However, there were also more adverse events associated with tocilizumab than placebo including the development of more infections, moderate-to-severe neutropenia, and a transient increase in transaminases. The authors conclude that treatment with IL-6 inhibition is effective in severe, persistent JIA but the benefits of this treatment have to be weighed against the increased risks.A prior commentary in AAP Grand Rounds2 highlighted treatment recommendations based on existing evidence and consensus expert opinion, the first such recommendations published for a pediatric rheumatic disease.2 Options for treating systemic JIA have now been expanded by published reports of both tocilizumab and canakimumab, an anti-interleukin-1β monoclonal antibody.1,3 This is a remarkable advancement for pediatric rheumatology, especially considering the impressive response achieved with both agents. In the canakimumab trial, 84% of canakimumab-treated patients achieved JIA ACR30 at 15 days compared to 10% of placebo, and there was a lower rate of flare in these patients compared to placebo (26% vs 75%).3The results for the tocilizumab study are especially impressive because the studied patients were generally sicker than those in the canakinumab study, with longer disease duration (median >5 years), more active joints (>16), and greater numbers of patients having failed prior treatment with biologic agents and other disease-modifying antirheumatic drugs. Half of these patients were able to discontinue glucocorticoids and 59% achieved JIA ACR90 after 52 weeks.Adverse events and laboratory abnormalities were more common in the biologic treatment arms in both studies and included thrombocytopenia and neutropenia with canakimumab and neutropenia and elevated transaminases with tocilizumab. Infections were more common in the biologic arms but all of these resolved without sequelae. Although more study is needed to better assess the risk:benefit ratio of these treatments for systemic JIA, it is exciting to report increasing therapeutic options for patients suffering from an often life-altering condition such as systemic JIA.
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Jun 1, 2013
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