Low-dose methotrexate can be associated with ‘small to moderate’ elevations in risk for skin cancer and pulmonary, gastrointestinal, haematological and infectious adverse effects (AE), US researchers say.

The investigators from Brigham and Women’s Hospital in Boston, Massachusetts, conducted a prespecified analysis of methotrexate toxicities using data from the Cardiovascular Inflammation Reduction Trial (CIRT).

In that trial, nearly 4800 patients with CVD and either type 2 diabetes or metabolic syndrome, but without rheumatic disease, who tolerated low-dose methotrexate (up to 20mg/week) during a run-in period were randomly assigned to continue on methotrexate or receive placebo. Everyone also received folic acid supplementation.

Over a median follow-up of nearly two years, 87% of those in the methotrexate arm had an AE of interest compared with 81.2% in the placebo arm.