Fast track — ArticlesMethotrexate and mortality in patients with rheumatoid arthritis: a prospective study
Introduction
Rheumatoid arthritis is a chronic progressive disease associated with systemic inflammation. The disease directly affects physical function and mobility and results in substantial short-term and long-term morbidity. Furthermore, individuals with rheumatoid arthritis have a substantially shorter life expectancy than does the general population.1, 2, 3 Deaths from cardiovascular disease, infection, and cancer are increased among individuals with rheumatoid arthritis.1, 2, 3, 4
A number of disease-modifying antirheumatic drugs exist, and low-dose methotrexate is the main choice.5 Although results of many clinical trials and their follow-up studies suggest that these drugs, including methotrexate, are effective in reducing morbidity measures (rheumatoid arthritis specific outcomes and relevant quality of life measures), their effect on mortality in patients with rheumatoid arthritis remains unknown. Our aim was to assess the potential survival benefit conferred by methotrexate given to individuals with rheumatoid arthritis.
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Study data
Since 1974, we have enrolled more than 2000 consecutive individuals with rheumatoid arthritis seen at the Wichita Arthritis Center, an outpatient rheumatology facility. We entered details of participants into a computerised database at the time of their first clinic visit, and obtained and added demographic (education level, smoking history, total income, and marital status), clinical (tender joint count, grip strength, morning stiffness, health assessment questionnaire disability index score,6
Results
1240 individuals with rheumatoid arthritis met our inclusion criteria. The mean length of follow-up until death or censoring was 6 years (SD 5; 91 007 total person-months). By the end of follow-up, 588 patients had received methotrexate (mean dose 13 mg per week; maximum dose 25 mg per week) and 191 had died. Of these 191 participants, 72 had been treated with methotrexate (37 594 exposed person-months). The mean number of months between clinic visits was 3·3 (2·3) in methotrexate users and 3·6
Discussion
Our results indicate that methotrexate was initiated more often in individuals who had severe rheumatoid arthritis. After adjustment for this confounding factor, we noted a 60% reduction in risk of mortality in patients treated with methotrexate. By contrast, we did not observe a comparable reduction in mortality associated with other conventional disease-modifying antirheumatic drugs, suggesting that there might be a differential survival benefit with methotrexate.
Cardiovascular deaths were
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