By Robert Preidt
But until now there's been little comprehensive research on side effects tied to the drug.
A new study funded by the U.S. National Institutes of Health may fill that gap. It finds that patients who take methotrexate do have a slight-to-moderate increased risk of certain types of side effects.
"Methotrexate is a cornerstone drug for a variety of inflammatory diseases, especially for rheumatoid arthritis," Dr. Daniel Solomon, a rheumatologist at Brigham and Women's Hospital in Boston, said in a hospital news release. His team noted that the medicine has been in use for 40 years.
To learn more about side effects, the researchers analyzed data gathered on nearly 4,800 people. All had participated in a study focused on cardiovascular inflammation, and they took either a "dummy" placebo or low-dose methotrexate combined with folate.
Of the nearly 2,400 participants who took methotrexate, 87% had a notable side effect, compared with 81.5% of those who took a placebo, the study found.
People who took methotrexate had small-to-moderate increases in risks for skin cancer, infections, and gastrointestinal, lung and blood problems, according to the study published Feb. 17 in the Annals of Internal Medicine.
The researchers said the most surprising finding was that patients who took methotrexate were twice as likely to develop skin cancer as those who took a placebo -- 53 incidents versus 26, respectively.
That result was of concern to one expert in psoriasis care.
"Methotrexate is a common drug prescribed by dermatologists and rheumatologists, especially for patients with psoriatic arthritis," said Dr. Michele Green, who wasn't involved in the new research. Psoriatic arthritis is a form of arthritis that affects people with psoriasis.
"What is surprising and important in this study is the finding of a doubling of the rate of skin cancer in patients taking methotrexate," said Green, a dermatologist at Lenox Hill Hospital in New York City. "Patients with psoriatic arthritis are already at an increased risk of skin cancer. This new information should call for higher skin cancer screening of all patients taking methotrexate."
The study also found an increase in liver test abnormalities and five cases of cirrhosis among patients who took methotrexate, results that echo previous research.
None of the findings mean that patients need to quit taking methotrexate if it is helping them, Solomon stressed.
"We definitely wouldn't suggest this drug is too dangerous to give. But having a clear side-effect profile allows us to give it with eyes wide open and better balances the risks and benefits of an age-old drug," he said.
"Over the decades, we've learned about the side effects but only from small studies," Solomon noted. "Questions for both physicians and patients have lingered about the drug's safety. Our study offers a detailed side-effect profile that I think will help us prescribe methotrexate in an informed way."