Vol.19 No.1

Review Article

Methotrexate for the treatment of juvenile idiopathic arthritis: process to approval for JIA indication in Japan


Masaaki Mori1 , Takuya Naruto1 , Tomoyuki Imagawa1 , Takuji Murata2 , Syuji Takei3 , Minako Tomiita4 , Yasuhiko Itoh5 , Satoshi Fujikawa6 , Shumpei Yokota1

  • Department of Pediatrics, Yokohama City University School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, Kanagawa 236-0004, Japan
  • Department of Pediatrics, Osaka Medical College, Takatsuki, Japan
  • School of Health Sciences, Faculty of Medicine, Kagoshima University, Kagoshima, Japan
  • Department of Pediatrics, Graduate School of Medicine, Chiba University, Chiba, Japan
  • Department of Pediatrics, Nippon Medical School, Tokyo, Japan
  • Institute of Rheumatology, Tokyo Women’s Medical University, Tokyo, Japan

22 May 2008


19 August 2008

Published online:

25 September 2008

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Methotrexate (MTX), the primary treatment for the articular-type juvenile idiopathic arthritis (JIA), is effective and brings about radiological improvement. Patient compliance is good, and it is recognized that its known side effects, namely, disruption of liver function and induction of pulmonary lesions, are unlikely to be severe at the low MTX doses that are administered. In Japan, MTX was granted approval in 1999 by the then Ministry of Health and Welfare specifically for treating rheumatoid arthritis in adult patients, allowing it be generally used in medical institutions for patients having National Health Insurance. However, in the pediatric field, its use outside the indications has so far been unavoidable, and has been left to the discretion of the physician. Finally, at the present conference, expansion of the indications of MTX for JIA was approved in Japan. It is noteworthy that this expansion of indications was achieved without requiring clinical trials on children sponsored by the pharmaceutical company: it was achieved rather by collecting necessary information through ongoing efforts (including collection and analysis of information about approval status in foreign countries, adequate evidence from the literature, implementation of a clinical use survey in Japan, etc.). It also merits attention that the maximum dose (10 mg/m2) was set on the basis of pharmacokinetic data from children, rather than relying on the dosing method and dose for adults.

Key words

Juvenile idiopathic arthritis - Childhood - Methotrexate - Expansion of indication