Shigeki Katakura

Clinical Study of Tocilizumab in Children With Systemic-Onset Juvenile Idiopathic Arthritis

Systemic-onset juvenile idiopathic arthritis (sJIA) is a severe and steroid-dependent disease of unknown etiology that sometimes progresses to a fatal disease known as the macrophage activation syndrome. The investigation of inflammatory cytokines and receptor levels revealed an increase in interleukin (IL)-6 and soluble IL-6 receptor (sIL-6R) in serum of patients with active sJIA. The clinical symptoms and signs of the disease are presumably attributable to the continuous elevation of IL-6 and sIL-6R levels in serum. The characteristic fever spikes parallel IL-6 levels. In children, a long-term exposure to high levels of IL-6 causes severe growth impairment, as suggested by recently established studies of IL-6 transgenic mice.The biological functions of IL-6 are expressed through the binding of IL-6/IL-6R complex to gp130. The administration of tocilizumab (a recombinant humanized anti-IL-6R monoclonal antibody) exerts its action by preventing the binding of IL-6 to its receptor and, therefore, preventing the activation of gp130.After a few cases of compassionate use of tocilizumab, phase I and II studies of tocilizumab were conducted in children with sJIA, revealing that tocilizumab abruptly reduced the typical symptoms of inflammation and improved laboratory abnormalities. This article describes the experience in Japan regarding the treatment of sJIA with tocilizumab and supports the hypothesis that high levels of IL-6 may play an important role in the pathogenesis and maintenance of this disease. A confirmation of the role of tocilizumab in the treatment of sJIA will be provided by the results of the ongoing phase III study in Japan.

Transient remission of intractable systemic-type of juvenile rheumatoid arthritis after chickenpox in a 2-year-old boy.

collagen diseases in children.1 However, the pathogenesis of the disease remains unclear. We sometimes experience intractable cases with a systemic-type of JRA, which is refractory to several antirheumatic drugs, including acetyl salicylic acid (ASA), prednisolone (PSL), gold, methotrexate (MTX) and even cyclosporine A (CsA). In contrast, chickenpox is a common infectious disease in children. Chickenpox rarely presents with any severe complications, such as hemophagocytic syndrome.2 Recently, we experienced a case of intractable systemictype JRA, who went into transient remission after contracting chickenpox. To our knowledge, this type of phenomenon in JRA has not been previously reported and this case may contribute to the understanding of the pathogenesis of the disease, including the importance of the balance between T helper (Th) 1 and Th2 cells in JRA, and to develop a new therapeutic strategy for the treatment of the condition.

Methotrexate therapy for juvenile rheumatoid arthritis in Japan — surveillance with a questionnaire at seven main facilities

Methotrexate (MTX) therapy is now a main-stream drug for the treatment of patients with rheumatoid arthritis (RA). Similarly, the therapy is being established in the treatment of juvenile rheumatoid arthritis (JRA). However, little is known about the therapy for JRA in Japan. Therefore, to establish MTX therapy for JRA we investigated the current state of therapy in Japan. In September 1996 a questionnaire about MTX therapy was sent to the main facilities in Japan where members of the Japan Pediatric Rheumatology Association have been treating patients with JRA. From seven main facilities, a total of 56 JRA patients treated with MTX were reported. From this survey, it was revealed that MTX was used frequently for the treatment of patients with JRA in combination with other drugs such as non-steroidal anti-inflammatory drugs and prednisolone. MTX therapy was determined effective in 80% of cases; moreover, this therapy was tolerable in most cases. However, there were a few mild adverse effects including hepatotoxicity. Thus, MTX therapy was applied broadly to JRA patients in Japan. The therapy was determined to be more effective than prior medications when combined with other drugs to treat JRA.

Long-term remission in three patients with childhood-onset systemic lupus erythematosus

Abstract Three cases of childhood-onset systemic lupus erythematosus (childhood SLE) with long-term remission are reported. These cases were not complicated with collagen diseases and had no SLE disease activity index scores either 3 or 5 years after onset. We suggest that some patients with childhood SLE may be able to abandon the maintenance therapy, and that careful observation is needed for each individual case. Uniform remission criteria based on clinical trials are needed.