Key clinical point: Patients taking LD-MTX have a small-to-modest increase in the risk of some adverse events, including gastrointestinal, infectious, and hematologic.

Major finding: The relative rate of an adverse event of interest was 17% higher in the LD-MTX group than in the placebo group (HR, 1.17; 95% CI, 1.10-1.25).

Study details: A double-blind, placebo-controlled, randomized trial of 4,786 patients with known cardiovascular disease and diabetes or metabolic syndrome.

Disclosures: The National Institutes of Health funded the study. Various authors reported receiving grants from the National Heart, Lung, and Blood Institute, along with grants, research support, and personal fees from numerous pharmaceutical companies before and during the study. Dr. Bykerk reported receiving personal fees, grants, and nonfinancial support from pharmaceutical companies, foundations, and the NIH.

Commentary

“Low-dose methotrexate (10-25 mg weekly) is a first-line treatment used for RA and other autoimmune conditions but has been associated with pulmonary, hematologic, and gastrointestinal adverse effects. This study examines the adverse event rates among participants in the recently published randomized, double-blind, placebo-controlled CIRT trial, which looked at cardiovascular event rates among patients taking methotrexate. Adverse event rates were reported at high rates among patients in both the placebo and methotrexate arms, but were more common with methotrexate, with the large majority of these reactions being “mild.” Specifically, liver enzyme elevations were common among patients receiving methotrexate, with most of these, again, being mild elevations. Of note, the patients in this study did not have rheumatoid arthritis, but the information presented here is a helpful summary of commonly-observed methotrexate side effects that can serve as a starting point for counseling patients prior to and during therapy.”

Arundathi Jayatilleke, MD

Lewis Katz School of Medicine, Temple University