The side effects of some immunosuppressive drugs, such as Trexall, Xatmep and Otrexup, may increase the risk of skin cancer and may cause other adverse health effects, such as gastrointestinal and pulmonary problems, according to the findings of a new study.
Researchers with Brigham and Women’s Hospital and the Hospital for Special Surgery published findings last month in the Annals of Internal Medicine, which raise concerns over the side effects of Trexall and similar methotrexate-based drugs.
According to the data, even low doses of the drugs, used to treat rheumatoid arthritis, could significantly increase the risk of adverse health events, and the drugs are often used at much higher doses in cancer patients.
Methotrexate has been on the market for decades. It was first approved by the FDA in 1953, and is used to treat various forms of cancer, as well as rheumatoid arthritis and psoriasis. However, it is considered highly toxic.
“Low-dose methotrexate is the most commonly used drug for systemic rheumatic diseases worldwide and is the recommended first-line agent for rheumatoid arthritis,” the researchers noted. “Despite extensive clinical use for more than 30 years, few data on adverse event (AE) rates derive from randomized, placebo-controlled trials, where both causality and magnitude of risk can be inferred.”
Researchers conducted a double-blind, placebo-controlled, randomized trial involving 6,158 patients, some of whom were given 20 milligrams or less of low-dose methotrexate (LD-MTX), and some of whom were given a placebo. All of the participants received 1 mg/day of folic acid for six days per week and all had either known cardiovascular disease and diabetes, or metabolic syndrome.
According to the findings, 87% of those given drugs like Trexall and Xatmep and an adverse health effect of interest, compared with only about 81% of those given a placebo. Those given the immunosupressants had twice the risk of skin cancer, a 91% increased risk of gastrointestinal problems, a more than 50% increased risk of pulmonary problems and a 15% increased risk of infections or hematologic adverse events when compared to the placebo, the findings suggest.
The study found no increased risk of other forms of cancer, nor of neuropsychiatric, mucocutaneous or musculoskeletal adverse effects, and those taking LD-MTX had a reduced risk of kidney problems, according to the data.
In December 2019, the Institute for Safe Medication Practices published a report warning that patients are often confused by the dosing instructions for methotrexate-based drugs, leading to medication errors which can result in serious adverse health effects, including death.
ISMP researchers found that use of methotrexate has increased significantly in recent years. They estimate that the number of patients on the various forms of the drug doubled from just over 500,000 in 2013 to more than 1 million in 2017.