Low-dose MTX is the most commonly used drug for systemic rheumatic diseases worldwide and is the recommended first-line agent for rheumatoid arthritis,” the researchers said. “Despite extensive clinical use for more than 30 years, few data on adverse event rates derive from randomized, placebo-controlled trials, where both causality and magnitude of risk can be inferred.”
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They compared the adverse event rates, risk, and risk difference between low-dose MTX and placebo among 4786 participants with known cardiovascular disease and diabetes or metabolic syndrome. A total of 2391 participants were randomly assigned to low-dose MTX (less than 20 mg per week) and 2395 were randomly assigned to placebo. In addition, all participants received folic acid 6 days per week. The median follow-up was 23 months, and median dosage was 15 mg per week.
Among participants treated with low-dose MTX, 2080 (87%) had an adverse event of interest compared with 1951 (81.5%) who received placebo (hazard ratio [HR] 1.17; 95% CI, 1.10-1.25).
Compared with placebo, the researchers found the relative hazards of gastrointestinal (HR 1.91; 95% CI, 1.75-2.10), pulmonary (HR 1.52; 95% CI, 1.16-1.98), infectious (HR 1.15; 95% CI, 1.10-1.30), and hematologic (HR 1.15; 95% CI 1.07-1.23) adverse events were elevated with low-dose MTX. However, they found low-dose MTX was associated with reduced renal adverse events (HR 0.85; 95% CI, 0.78-0.93).
The risk for mucocutaneous, neuropsychiatric, musculoskeletal, and non-skin cancers did not different between low-dose MTX and placebo groups, the researchers said. However, skin cancer was increased among the low-dose MTX group (HR 2.05; 95% CI, 1.81-3.28).
Use of [low-dose MTX] was associated with small to moderate elevations in risks for skin cancer and gastrointestinal, infectious, pulmonary, and hematologic AEs, whereas renal AEs were decreased,” the researchers concluded.
Solomon DH, Glynn RJ, Karlson EW, et al. Adverse effects of low-dose methotrexate: A randomized trial [published online February 18, 2020]. Ann Intern Med. doi:10.7326/M19-3369
Wed, 02/19/2020 - 19:49