Risk factors associated with the cumulative survival of low-dose methotrexate in 273 Japanese patients with rheumatoid arthritis.
BACKGROUND
Methotrexate (MTX) has become the most commonly prescribed disease-modifying antirheumatic drug (DMARD) for the treatment of rheumatoid arthritis (RA). In the Western countries, the MTX dosage is safely increased to a maximum of 25 mg/wk until a significant response is observed. On the contrary, in Japan, MTX has been approved only as a second-line agent, and the approved maximum MTX dosage is only 8 mg/wk. This suboptimal dosage may affect MTX survival in Japanese RA patients.


OBJECTIVE
To study risk factors associated with the cumulative survival of MTX in Japanese RA patients.


METHODS
Data on 273 patients (male 44, female 229) with RA treated with MTX between January 1, 2000 and September 30, 2004 in our center were studied.


RESULTS
Two hundred seventy-three patients were followed for 437 person-years of MTX exposure. Mean MTX dosage was 5.5 +/- 1.9 mg/wk. The cumulative MTX survival probability after 5 years was 61.9%. Univariate Cox regression analysis showed a significant correlation between MTX survival probability and use of fewer previous DMARDs, higher dose of MTX, inclusion of folate supplementation, and shorter disease duration. In the multivariate Cox regression model, use of fewer previous DMARDs remained significantly related to MTX survival. Reasons for discontinuation included adverse effects in 34 patients (12.5%) and inefficacy in 6 patients (2.2%).


CONCLUSIONS
Cumulative survival was the same or slightly better than those in reports from Western countries, with less withdrawals reported due to adverse events or inefficacy. Whether these results are due to different MTX needs in Japanese or to acceptance of less clinical efficacy will require further studies. The use of fewer previous DMARDs was associated with longer MTX survival.
Ideguchi
Haruko
H
Chronic Intractable Disease Center, Yokohama City University Medical Center, Yokohama, Kanagawa, Japan.
Ohno
Shigeru
S
Ishigatsubo
Yoshiaki
Y
D000293:Adolescent; D000328:Adult; D000368:Aged; D018501:Antirheumatic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007564:Japan; D008297:Male; D008727:Methotrexate / Q000009:adverse effects / Q000627:therapeutic use*; D008875:Middle Aged; D015999:Multivariate Analysis; D012189:Retrospective Studies; D012307:Risk Factors; D016019:Survival Analysis; D016896:Treatment Outcome
D018501:Antirheumatic Agents; D008727:Methotrexate