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Common Rheumatoid Arthritis Drug Won't Raise Blood Cancer Risk
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But a lesser-used medicine, cyclophosphamide, was associated with a doubling in patients' odds for lymphoma, the Canadian researchers found.
The study of almost 24,000 patients over 23 years of age showed no clear association between methotrexate and cancers of the blood, such as lymphoma. Methotrexate has been long and widely used by many patients with rheumatoid arthritis.
There was an elevation in cancer risk with cyclophosphamide, which is sometimes used to treat very severe rheumatoid arthritis that has progressed to the point of threatening or damaging organs.
The results, "add to the literature regarding the cancer risk associated with cyclophosphamide and emphasizes that we need to continue to develop safer drugs for very severe forms of autoimmune disease," said study lead author Dr. Sasha Bernatsky, an epidemiologist at McGill University in Montreal. Her team published its findings in the Feb. 25 issue of the Archives of Internal Medicine.
Bernatsky added that it is important to recognize with cyclophosphamide that "even though the risk of certain cancers in some autoimmune disease is elevated, these cancers are still relatively rare—much less than 1 percent. People should not stop taking their drugs if their specialists really feel that they need these drugs."
Bernatsky said such patients need to, "keep in mind that cyclophosphamide has been demonstrated to have overall benefits in some cases, such as preserving kidney function when kidneys are affected by autoimmune disease."
Rheumatoid arthritis, which affects an estimated 1.3 million Americans, is a chronic inflammatory disease in which the body's autoimmune system most commonly attacks the joints, according the Arthritis Foundation. According to the study, over the past 30 years, doctors have noted an increased risk for lymphoma in patients with rheumatoid arthritis, although the exact reasons for that phenomenon remain unclear.
In the new study, the Montreal team looked at the medication use of almost 24,000 patients with rheumatoid arthritis to see if the connection might lie there. They compared rates of leukemia and lymphoma for this group for the years 1980 to 2003 against a much larger group of people unaffected by rheumatoid arthritis.
A total of 619 blood cancers (more than half of which were lymphomas) were noted among the rheumatoid arthritis patients over the study period.
Bernatsky's team found no association between the use of methotrexate and blood cancer risk, but the odds that a patient would develop a lymphoma more than doubled with use of cyclophosphamide.
Other experts agreed that the study's findings supported earlier research that had been reassuring about the impact of methotrexate. They also agreed on the need for patients and their doctors to weigh benefit and risk when considering cyclophosphamide.
Dr. Stephen Lindsey, chief of rheumatology at the Ochsner Clinic Foundation in Baton Rouge, La., said that the results on methotrexate seem "to be good news for the majority of rheumatoid arthritis patients, because they're almost all on that."
People need to recognize that rheumatoid arthritis is more than a few aching joints, he added. The disease can involve an increased risk of mortality—in fact, patients with severe cases die an average of 10 years earlier than their peers, Lindsey said. And, he noted that rheumatoid arthritis has long been tied to an increased risk of lymphoma, separate from any risk associated with medication. Many lymphomas are curable, he said, another factor to think about when weighing the cyclophosphamide risk-benefit equation.
Dr. W. Hayes Wilson, a rheumatologist in Atlanta who is a national medical adviser for the Arthritis Foundation, added that the risks of cyclophosphamide have been recognized for years, although he personally could not recall any of his patients developing the blood cancer.
According to Wilson, cyclophosphamide is no one's first choice for treatment and is only used in the more severe cases. "You're sort of choosing between two evils," Wilson said. "No one wants to jump out of a perfectly good airplane, but if that airplane had two engines, and one was on fire, I might strap on that parachute and jump."
The study did not present data on any risks associated with new biologic medications, such as Embrel, Humira, and Remicade, which have been available since about 2000, Lindsey and Wilson said. There have been other studies with positive results for one category of these drugs, called TNF-alpha inhibitors, Wilson said. For severe cases, "when we treat them aggressively with a biologic modifier, perhaps we are bringing their risk down to similar to the general population," he said.
SOURCES: Sasha Bernatsky, M.D., division of clinical epidemiology, McGill University Health Centre, Montreal; Stephen Lindsey, M.D., chief, rheumatology, Ochsner Clinic Foundation, Baton Rouge, La.; W. Hayes Wilson, M.D., National Medical Adviser, Arthritis Foundation, and chief, rheumatology, Piedmont Hospital, Atlanta; Feb. 25, 2008, Archives of Internal Medicine
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