Clinical study of tocilizumab in children with systemic-onset juvenile idiopathic arthritis |
| |
Authors: | Shumpei Yokota Takako Miyamae Tomoyuki Imagawa Shigeki Katakura Rumiko Kurosawa Masaaki Mori |
| |
Institution: | (1) Department of Pediatrics, Yokohama City University School of Medicine, Yokohama, Kanagawa, Japan |
| |
Abstract: | 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. |
| |
Keywords: | Pro-inflammatory cytokine juvenile idiopathic arthritis antirheumatic drugs anti-IL-6 receptor monoclonal antibody corticosteroids |
本文献已被 PubMed SpringerLink 等数据库收录! |
|