Response to Methotrexate Treatment is Associated with Reduced Mortality in Patients with Severe Rheumatoid Arthritis

Objective: This study investigated whether efficacious methotrexate (MTX) treatment has an impact on mortality of patients with severe rheumatoid arthritis (RA).

Methods: In this prospective, observational, one-center study, patients with severe RA refractory to other disease-modifying antirheumatic drugs started MTX treatment between 1980 and 1987. Patients were divided into 4 different groups according to their response to MTX treatment after 1 year (>50% improvement [n = 99], 20-50% improvement [n = 70], no improvement [n = 52], and discontinued treatment [n = 35]). After a followup of 7.5-15.3 years (mean 10 years), the numbers of deaths were assessed in the different groups. Standardized mortality ratios (SMR) were calculated by comparing the number of observed deaths in the study with the number of expected deaths in an age- and sex-matched sample of the general population.

Results: Two hundred seventy-one patients entered the study between 1980 and 1987. In 1995/1996, outcomes for 256 patients (94.5%) could be documented; 88 patients (34.4%) had died. In patients with >50% improvement after 1 year, the SMR was 1.47, while in patients with 20-50% improvement, the SMR was 1.85. In both groups combined, the SMR was 1.64 (95% confidence interval [95% CI] 1.11-2.17), compared with 4.11 (95% CI 2.56-5.66) in patients without improvement. Patients who had discontinued MTX treatment during the first year had an SMR of 5.56 (95% CI 3.29-7.83).

Conclusion: Patients with severe RA who do not respond to MTX treatment have a poor prognosis, with >4-fold increased mortality compared with the general population, while RA patients who respond to MTX treatment have only a moderately increased mortality rate.