Methotrexate may decrease rates of large-joint replacement in RA patients taking TNF inhibitors

Patients with rheumatoid arthritis (RA) treated with tumor necrosis factor (TNF) inhibitors may have lower rates of large-joint replacement when also taking methotrexate, a new study indicates.

Researchers in Japan performed a retrospective cohort study of patients with RA taking etanercept or adalimumab to examine the effect of concomitant methotrexate therapy on the incidence of large-joint replacement due to progression of large-joint destruction. The outcome variable in predictive analyses was the first large-joint replacement that occurred during treatment with etanercept or adalimumab. The authors used Kaplan-Meier curves to estimate cumulative incidence of large-joint replacement and Cox proportional hazards models to assess the effect of methotrexate. The study results were published online April 1 by Arthritis Care & Research.

A total of 803 patients treated between April 1, 2005, and September 30, 2013, were included in the study, 530 of whom were taking etanercept and 273 of whom were taking adalimumab. Of these, 601 (75%) received concomitant methotrexate at a median dose of 8 mg/wk (interquartile range, 6 to 8 mg/wk). Patients were followed for a median of 2.9 years (interquartile range, 1.0 to 4.6 years); 37 (4.6%) were lost to follow-up. Forty-nine patients had large-joint replacement (62 joints) during etanercept or adalimumab treatment. Patients who were taking concomitant methotrexate had significantly lower incidence of large-joint replacement than patients who were not (P<0.001); this was also true in propensity score-matched analysis (P=0.032). In multivariate analysis, the hazard ratio for large-joint replacement was 0.36 (95% CI, 0.20 to 0.65) for patients receiving concomitant methotrexate versus those who were not.

The authors noted that their study had a retrospective cohort design and could have been subject to selection bias. They also pointed out that their sample size was small, that they did not assess radiographic data, and that the study was not designed to directly assess joint destruction. However, they concluded that concomitant treatment with methotrexate reduces incidence of large-joint replacement in RA patients who are taking TNF inhibitors. “Our results suggest that TNF inhibitors should be used preferentially in combination with [methotrexate] to inhibit the progression of both large and small joint destruction, and also strongly support recent [European League Against Rheumatism] recommendations,” the authors wrote. “Moreover, this study suggests that low dose [methotrexate] may have an additive effective on TNF inhibitors treatment for RA.”