Methotrexate May Decrease Risk for Ischemic Stroke in Rheumatoid Arthritis

MRI of brain showing blood vessels
MRI of brain showing blood vessels
A population based cohort study was used to examine the effects of hydroxychloroquine, sulfasalazine, and methotrexate on risk for ischemic stroke in rheumatoid arthritis.

Short-term methotrexate exposure at a dosage of >8.75 mg/week may be associated with a lower risk for ischemic stroke in patients with rheumatoid arthritis (RA) according to the results of a population-based retrospective cohort study published in the International Journal of Rheumatic Diseases.

Patients with RA have a mortality rate that is higher than that of sex- and age-matched controls. Among possible causes of death are infections, cardiovascular diseases, and renal diseases. Recent evidence has suggested that the inflammatory response seen in RA may contribute to cerebral ischemic injury.

The study researchers conducted a study to investigate the effects of hydroxycholoroquine, sulfasalazine, and methotrexate on ischemic stroke in RA, based on data from 7904 patients with RA and 15,806 patients without RA from the National Health Insurance Research Database of Taiwan between 2000 and 2010.  

The investigators used univariate analyses to compare and evaluate the differences in disease-modifying anti-rheumatic drug usage and demographic variables in the two groups of patients. They performed Cox proportional hazard models and Schoenfeld residuals test to estimate the hazard ratios for ischemic stroke and proportional hazard assumptions of these drugs, respectively.

The hazard ratio for ischemic stroke was 1.21 (P <.01) in the RA case group compared with the control group, a significant difference that persisted throughout the 10-year period.  In patients with RA, while hydroxychloroquine demonstrated an insignificant protective effect on ischemic stroke, sulfasalazine and methotrexate were determined to have inconsistent effects during the 10 years. 

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The proportional hazard assumption test of methotrexate at >0.5 defined daily dose (8.75 mg/week) was violated at a significant level after adjustment (P =.0002).

The investigators concluded that while there may be a lower risk for ischemic stroke in patients with RA receiving methotrexate, hydroxychloroquine, and sulfasalazine had neutral effects.


Tam H-W, Chen C-M, Leong P-Y, et al. Methotrexate might reduce ischemic stroke in patients with rheumatoid arthritis: a population-based retrospective cohort study [published online January 25, 2018]. Int J Rheum Dis.. doi:10.1111/1756-185X.13267