Methotrexate My Decrease Rate of Mortality in Rheumatoid Arthritis (RA)
Numerous studies have shown that patients with RA have reduced life expectancy. For example, using the standardized mortality ratio (SMR) [the ratio of the observed number of deaths in the diseased population to the expected number of deaths in the general population], patients with RA have been found to have SMRs ranging between 2.2 2.7 in various studies.
Methotrexate (MTX) can reduce disease activity and radiologic progression, but little is known about its effect on mortality. In this study, the investigators analyzed the mortality of patients with longstanding, severe RA who began treatment with MTX for the first time as part of a prospective, long-term, observational study between 1980 and 1987, and who had been observed until 1995/96.
271 patients entered the study between 1980 and 1987. The average age was 56. 79% were women, 85% were rheumatoid factor positive, 95% had joint erosions, and the majority of patients had advanced disease (Steinbrocker anatomic stages III and IV). Patients had been treated with a mean of 1.8 disease modifying agents (DMARDs) before starting MTX treatment. Response to treatment was assessed at 12 months, and, where possible, again at the 1995/96 followup time. A 50% response was defined as: decrease of > 50% from baseline in number of swollen joints and in sedimentation rate (ESR), coupled with prednisone dose of < 5 mg qday.
| 50% resp. | 20-50% resp. | No resp. | |
| Clinical response at 12 mos. | 39% (105) |
27% (74) |
20% (55) |
| SMR at followup (1995/96) | 1.47 | 1.85 | 4.11 |
In 1995/96, information was obtained on 256 of the original 271 patients. Of these, 34% (88) had died. Of those still alive, 60% remained on MTX. The SMR was 1.47 in the group of patients who had shown > 50% response after one year of MTX; and 1.85 in the 20-50% responders; and 4.11 in the nonresponders. Kaplan-Meier estimate of the probability of survival was significantly greater in the group of patients with improvement after one year (> 20% response) compared to the nonresponders.
Editorial comment: This study suggests that effective MTX treatment enhances life expectancy even in severe advanced disease, as evidenced by the lower SMRs in the responders compared to nonresponders. Some of the weaknesses of the study are: 1) it is an observational study and the true dosing of MTX is unknown; and 2) the investigators assumed that the response at 12 months would be sustained throughout the course of the disease; this is a leap of faith.
Nonetheless, these results are very encouraging and in sync with the clinical impressions of many practicing rheumatologists. MTX is a good drug!!!
