Rheumatoid Arthritis Drug Linked to Cancer
Small Percentage Taking Methotrexate Develop Lymphoma, Other Cancers
WebMD News Archive
Nov. 16, 2004 -- For people with rheumatoid arthritis, methotrexate is the treatment of choice in reducing pain and inflammation. But there's evidence the drug can activate a virus that can increase the risk of lymphoma and similar cancers in some patients.
The study appears in this month's issue of the Journal of the National Cancer Institute.
A number of reports have linked methotrexate with lymphoma and similar cancers of the lymph glands, says senior researcher Shannon C. Kenney, MD, a microbiologist and infectious disease specialist with the Lineberger Comprehensive Cancer Center at the University of North Carolina at Chapel Hill.
Also, studies have shown that when rheumatoid arthritis patients quit taking methotrexate, their lymphoma went into regression, another sign that the drug directly contributes to the cancer, she tells WebMD. Some studies have indicated that the drug's immune-weakening effect places people at risk for viral-associated lymphomas.
Another factor in this story: Epstein-Barr virus (EBV), a herpes virus that is common among adults. Some 90% of adults are said to have EBV, which is associated with mononucleosis and other infections -- but in the vast majority of people, the virus remains latent, never causing an infection, says Kenney. EBV has also been linked with lymphoma.
In this newest study, methotrexate has been shown to activate latent EBV in cells infected with the virus, Kenney reports. High levels of circulating infectious particles of the EBV were also found in patients taking methotrexate for rheumatoid arthritis compared with patients taking other immune-weakening drugs.
Methotrexate and Lymphoma
In a series of laboratory tests involving cells with latent EBV virus, Kenney found that using methotrexate on cells that contained the latent Epstein-Barr virus activated the virus, causing an increase in the release of infectious EBV.
"An infectious form of the virus was released from the cells," she tells WebMD. "We were surprised by that. We had already shown that certain kinds of chemotherapy could induce release of a form of EBV, but none would allow the infectious virus to be released.
Kenney's colleagues also measured Epstein-Barr virus blood levels in 29 patients with rheumatoid arthritis, 12 with polymyositis, and 47 with Wegener granulomatosis (both are relatively rare inflammatory diseases). Some were taking methotrexate; some were taking other immune-suppressing medications.
They found that methotrexate activated the Epstein-Barr virus; the other rheumatoid arthritis medications -- including cyclosporine, cyclophosphamide, and prednisone -- did not markedly affect EBV activity, even when doses of these drugs were higher than normal, she reports.
Patients taking methotrexate had significantly higher EBV viral loads in their blood than patients taking other immune weakening drugs.
With methotrexate, it's different. "Methotrexate activates cells with the Epstein-Barr virus, but it doesn't prevent replication of the [virus]. So it spews out the virus in an infectious form," she explains.
Similar results were found with polymyositis patients. However, the pattern was not found with Wegener granulomatosis -- just as few lymphomas have been reported in these patients, she notes.
The data shows that methotrexate has a "unique ability" to trigger Epstein-Barr virus while also suppressing the immune system -- thereby triggering lymphoma in these patients, she adds.