Rheumatoid Arthritis Drug Linked to Cancer Small Percentage Taking Methotrexate Develop Lymphoma, Other Cancers]

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Rheumatoid Arthritis Drug Linked to Cancer

Small Percentage Taking Methotrexate

Develop Lymphoma, Other Cancers

 

 

 

By Jeanie Lerche Davis

WebMD Medical News

Reviewed

By Brunilda Nazario, MD

on Tuesday, November 16, 2004

 

 

 

 

webmd.com/content/article/97/104045.htm?z=3734_00000_1000_ts_01

 

 

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.

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