Tocilizumab: molecular intervention therapy in children with systemic juvenile idiopathic arthritis.
Systemic juvenile idiopathic arthritis (JIA) is a subtype of chronic childhood arthritis of unknown etiology, manifested by long-lasting systemic inflammation and complicated by joint destruction, functional disability and growth impairment. Macrophage activation syndrome is the most devastating complication, which is associated with serious morbidity. IL-6 has been hypothesized to be a pathogenic factor of this disease. The anti-IL-6 receptor monoclonal antibody, tocilizumab, was developed, and we investigated the safety and efficacy of tocilizumab in children with this disorder. The Phase II trial revealed that high-grade fever abruptly subsided and that inflammatory markers were also normalized. The dose of tocilizumab for systemic JIA was revealed to be 8 mg/kg at 2-week intervals. The Phase III trial, a placebo-controlled, double-blind study, indicated that patients in the tocilizumab group had sustained clinical measures of effectiveness and wellbeing, whereas most of those in the placebo group needed rescue treatment. The most common adverse events were symptoms of mild infections and transient increases of alanine aminotransferase. Serious adverse events were anaphylactoid reaction and gastrointestinal hemorrhage. Clinical and laboratory improvement in fever, sickness behavior, C-reactive protein gene expression and chronic inflammatory anemia in children with systemic JIA treated with tocilizumab indicated the possible roles played by IL-6 in this inflammatory disease. Thus, tocilizumab is generally safe and well tolerated. It might be a suitable treatment in the control of this disorder, which has so far been difficult to manage.
Yokota
Shumpei
S
Department of Pediatrics, Yokohama City University School of Medicine, Kanazawa-ku, Yokohama, Kanagawa, Japan. syokota@med.yokohama-cu.ac.jp
Kishimoto
Tadamitsu
T
D000707:Anaphylaxis / Q000209:etiology; D000740:Anemia; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D001171:Arthritis, Juvenile / Q000188:drug therapy* / Q000503:physiopathology; D002648:Child; D002986:Clinical Trials as Topic; D018450:Disease Progression; D005334:Fever; D006471:Gastrointestinal Hemorrhage / Q000209:etiology; D006801:Humans; D007239:Infections / Q000209:etiology; D019947:Receptors, Interleukin-6 / Q000037:antagonists & inhibitors / Q000276:immunology*
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D019947:Receptors, Interleukin-6; C502936:tocilizumab