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Short-term methotrexate course may lower stroke risk in RA

13 Feb 2018

Short-term treatment with methotrexate at >0.5 defined daily dose (8.75 mg/week) may help reduce the risk of ischaemic stroke in rheumatoid arthritis (RA) patients, while hydroxychloroquine and sulfasalazine have neutral effects, a retrospective study has found.

Researchers reviewed the medical records of 7,904 RA patients and 15,808 non-RA controls sampled from the National Health Insurance Research Database of Taiwan. They performed univariate analyses to evaluate the differences in disease-modifying antirheumatic drug (DMARD) usage and demographic variables between the two patients groups, as well as Cox proportional hazard analysis and Schoenfeld residuals test to test the association between ischaemic stroke and the use of DMARDs.

The mean age of the cohort was 53 years old, and majority of RA patients (70 percent) were women. Compared with controls, RA patients had a 21-percent higher risk of ischaemic stroke (hazard ratio [HR], 1.21; 95 percent CI, 1.10–1.34; p<0.01), and this significant difference persisted throughout the 10-year period.

In the RA group, hydroxychloroquine conferred an insignificantly protective benefit for ischaemic stroke. On the other hand, sulfasalazine and methotrexate had inconsistent effects over 10 years.

“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=0.0002),” researchers noted.

"Our results showed that methotrexate at >0.5 defined daily dose was associated with a lower risk of ischaemic stroke in the first 7 years (adjusted HR, 0.33; 0.17–0.63) and a higher risk of ischaemic stroke in the last 3 years (adjusted HR, 3.36; 1.70–6.61)," they said.

Being the most commonly used drug for RA, methotrexate has become the standard DMARD in clinical practice. However, not all patients tolerate it well or show an acceptable therapeutic response to it. Hepatotoxicity and bone marrow suppression are among the adverse effects associated with methotrexate. [BMJ 2003;326:266-267]

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