title: Methotrexate for the treatment of juvenile idiopathic arthritis: process to approval for JIA indication in Japan.
abstract: 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.
authors.affiliation: Department of Pediatrics, Yokohama City University School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, Kanagawa, 236-0004, Japan. mmori@med.yokohama-cu.ac.jp
authors.forename: Masaaki
authors.initials: M
authors.lastname: Mori
authors.forename: Takuya
authors.initials: T
authors.lastname: Naruto
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Imagawa
authors.forename: Takuji
authors.initials: T
authors.lastname: Murata
authors.forename: Syuji
authors.initials: S
authors.lastname: Takei
authors.forename: Minako
authors.initials: M
authors.lastname: Tomiita
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Itoh
authors.forename: Satoshi
authors.initials: S
authors.lastname: Fujikawa
authors.forename: Shumpei
authors.initials: S
authors.lastname: Yokota
mesh_terms: D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001171:Arthritis, Juvenile / Q000188:drug therapy* / Q000453:epidemiology; D017277:Drug Approval / Q000331:legislation & jurisprudence*; D006801:Humans; D007564:Japan / Q000453:epidemiology; D008727:Methotrexate / Q000627:therapeutic use*; D009017:Morbidity; D016896:Treatment Outcome
chemical_list: D018501:Antirheumatic Agents; D008727:Methotrexate