Response to methotrexate predicts long-term mortality of patients with rheumatoid arthritis independent of the degree of response: results of a re-evaluation 30 years after baseline.

OBJECTIVES: To assess if there is a correlation between the degree of response to treatment with methotrexate (MTX) and long-term mortality in a cohort of patients with rheumatoid arthritis (RA) established in Germany in the early eighties.

METHODS: RA patients who had started MTX treatment between 1980 and 1987 were included. One year after baseline, the treatment response was evaluated. Responders were defined as patients with at least 20% decline in the swollen joint count (out of 32 joints) and the ESR with a prednisone dosage <5 mg/day. Thereafter, assessments were performed at 10, 18, and 30 years after baseline. Standardised mortality ratios (SMR) were calculated, Cox regression and logistic regression were performed.

RESULTS: The cohort comprised 271 patients. In 2015, about 30 years after the initiation of MTX therapy, 185 patients (68%) were deceased, 52 (19%) lost to follow-up and 34 alive. The response after the first year of MTX treatment was the strongest predictor of survival with a hazard ratio of 0.44 (95% confidence interval [CI]: 0.30-0.65). However, even responders still had an SMR of 1.37 (95% CI 1.31-1.65), but this was much worse for non-responders who had an SMR of 4.22 (95% CI 3.13-5.56). Using Cox regression analysis no difference was detected between responders with more than 50% improvement (38% of all patients) and those with 20-50% improvement (28%).

CONCLUSIONS: The predictive value of a response to one year of MTX therapy for long-term mortality of RA patients is independent of the degree of response.