Rheumatoid arthritis patients with the most severe disease are roughly 70 times more likely to develop lymphoma, a type of cancer, than patients with mild disease, according to new research from Sweden.
The findings provide some of the best evidence yet linking the elevated lymphoma risk among rheumatoid arthritis (RA) patients to the disease itself and not the drugs used to treat it.
In fact, researchers suggest that the drugs Enbrel, Remicade, and Humira and other new and old treatments for RA may actually reduce the chances of developing lymphoma in high-risk patients by reducing inflammation.
“Conventional medical treatment to suppress and alleviate disease activity is not by itself a risk factor for lymphoma,” they write in the March 2006 issue of Arthritis and Rheumatism.
About 2 million Americans have rheumatoid arthritis, a progressive disease characterized by inflammation of the lining of the joints. The joint damage that occurs over time can lead to chronic pain and disability.
People with rheumatoid arthritis are roughly twice as likely as those without the disease to develop lymphoma, which is a broad term for a variety of cancers of the lymphatic system.
Researcher Eva Baecklund, MD, PhD, and colleagues drew from a Swedish national registry that included nearly 75,000 RA patients to conduct the study.
The researchers compared 378 RA patients diagnosed with lymphoma between 1964 and 1995 to an equal number of RA patients without lymphoma matched for age, time of RA diagnosis, and place of residence.
Patients with moderate inflammation were eight times more likely to develop lymphoma than patients with mild rheumatoid arthritis. Those with high RA activity were 70 times more likely to develop lymphoma.
“The association between lymphoma risk and very high and/or longstanding disease activity indicates that most patients with RA will never have any clinically relevant increased lymphoma risk,” Baecklund and colleagues write.
More than 70 percent of the RA patients included in the study had been treated with disease-modifying antirheumatic drugs (DMARDs) -- including the drug methotrexate, which was recently linked to an increased risk of Epstein-Barr virus-positive lymphomas in a French study.
But Baecklund and colleagues found no evidence linking methotrexate or any other DMARD to an increase in cancer risk. The same was true for nonsteroidal anti-inflammatory drugs and steroids.
Rheumatologist Daniel Solomon, MD, of Boston’s Brigham and Women’s Hospital, tells WebMD that there has been particular concern that some newer DMARDs may cause lymphomas.
The research by Baecklund and colleagues has been reassuring, he says, but there are still unanswered questions that will be difficult to answer.
“There is a lot of interest in whether [lymphoma risk] is drug-related or disease-related,” he says. “It is the $64,000 question and we don’t yet have the answer. It will be a hard issue to disentangle.”
By Salynn Boyles, reviewed by Louise Chang, MD
SOURCES: Baecklund, E. Arthritis & Rheumatism, March 2006; vol 54: pp 692-701. Eva Baecklund, MD, PhD, department of rheumatology, Akademiska Hospital, Uppsala, Sweden. Daniel Solomon, MD, MPH, rheumatologist; assistant professor of medicine, division of pharmacoepidemiology, Brigham and Women's Hospital, Boston.