Researchers Identify AEs Associated With Low-Dose Methotrexate

Patients who receive low-dose methotrexate (MTX) may be at a small to moderately increased risk for skin cancer as well as gastrointestinal, infectious, pulmonary, and hematologic adverse events (AEs), according to a new study analysis.¹

To evaluate the association between low-dose MTX and AEs, the study authors analyzed data on 4786 participants with known cardiovascular disease and diabetes or metabolic syndrome who had been randomly assigned to receive either low-dose MTX (≤20 mg/wk) or placebo. All participants had received folic acid, 1 mg, daily for 6 days per week. 

The median follow-up was 23 months, and the participants had received a median MTX dosage of 15 mg/wk.

The participants did not have rheumatic disease and had tolerated low-dose MTX during the active run-in period. Among the participants, 81.2% were men, the median age was 65.7 years, and the median body mass index was 31.5 kg/m².

Of the 2391 participants assigned to low-dose MTX, 2080 (87.0%) had had an AE of interest. Participants in the placebo group were less likely to have had an AE, with 1951 of the 2395 group participants (81.5%) having experienced an AE of interest.

Compared with the placebo group, the low-dose MTX group had elevated relative hazards for the following AEs: 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, 1.01-1.30), and hematologic (HR, 1.15; 95% CI, 1.07-1.23).

The groups did not differ in their risk of mucocutaneous, neuropsychiatric, or musculoskeletal AEs. And the only cancer risk that differed between the groups was skin cancer, with those in the low-dose MTX group having an increased risk (HR, 2.05; 95% CI, 1.28-3.28).

Meanwhile, participants in the low-dose MTX group experienced a decrease in renal AEs (HR, 0.85; 95% CI, 0.78-0.93).

—Colleen Murphy

Reference:

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.