title: Association of higher methotrexate dose with lymphoproliferative disease onset in rheumatoid arthritis patients.
abstract: OBJECTIVE
  Methotrexate (MTX) is used as an anchor drug for rheumatoid arthritis (RA). Lymphoproliferative disease (LPD) occasionally develops in patients treated with MTX, and is known as MTX-associated LPD (MTX-LPD). Although MTX-LPD occurs mainly in RA patients, it has not been established if MTX administration is an independent risk factor for LPD in RA patients. We examined the clinical characteristics of MTX-LPD in Japanese RA patients and attempted to determine the risk factors for MTX-LPD development.
  
  
  METHODS
  We performed a nested case-control study on RA patients. We enrolled 5,753 RA patients from Kagawa, Japan. In age- and sex-matched patients, we separated patients who did not develop LPD under MTX treatment (MTX non-LPD group) from those that did (MTX-LPD group) and conducted a comparative examination. We used multivariate analysis to determine the independent risk factors for MTX-LPD onset.
  
  
  RESULTS
  There were 28 patients in the MTX-LPD group and 125 patients in the MTX non-LPD group. Multivariate analysis of the parameters extracted by univariate analysis revealed that the mean MTX dose was a risk factor for MTX-LPD after adjusting for age; therefore, higher MTX dose is associated with LPD onset in RA patients.
  
  
  CONCLUSIONS
  MTX is an independent risk factor for LPD onset in Japanese RA patients.
authors: Kagawa University, Kagawa, Japan.
authors: Tomohiro
authors: T
authors: Kameda
authors: Hiroaki
authors: H
authors: Dobashi
authors: Nobuyuki
authors: N
authors: Miyatake
authors: Masayuki
authors: M
authors: Inoo
authors: Ikuko
authors: I
authors: Onishi
authors: Noriyuki
authors: N
authors: Kurata
authors: Hiroki
authors: H
authors: Mitsunaka
authors: Kimihiro
authors: K
authors: Kawakami
authors: Tetsuya
authors: T
authors: Fukumoto
authors: Kentaro
authors: K
authors: Susaki
authors: Miharu
authors: M
authors: Izumikawa
authors: Shusaku
authors: S
authors: Nakashima
authors: Hiromi
authors: H
authors: Shimada
authors: Yohei
authors: Y
authors: Takeuchi
authors: Reiji
authors: R
authors: Haba
authors: Shohei
authors: S
authors: Mano
authors: Hiroaki
authors: H
authors: Onishi
authors: Osamu
authors: O
authors: Imataki
authors: Takuya
authors: T
authors: Matsunaga
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D018501:Antirheumatic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D008232:Lymphoproliferative Disorders / Q000139:chemically induced*; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D008875:Middle Aged; D012307:Risk Factors
chemical_list: D018501:Antirheumatic Agents; D008727:Methotrexate