TUESDAY, May 16, 2006 (HealthDay News) -- Rheumatoid arthritis patients treated with new and potent "TNF-blocking" drugs are at higher risk of developing cancer and serious infections, according to a new review of the available data.
"This is the clearest indication that we have that the drugs contribute to the risk," said senior study investigator Dr. Eric Matteson, a professor of medicine and consultant in rheumatology at the Mayo Clinic in Rochester, Minn.
Other experts still question whether it is the drugs that are responsible for the heightened risk, or if the disease itself is responsible.
"It's just hard to sort out the malignancy issue on this," said Dr. Stephen Lindsey, head of rheumatology at Ochsner Health System in Baton Rouge, La. "Do we really know if it's the medicine itself or the fact that these patients [taking this therapy] are the sickest? We're still trying to sort out the degree to which medicine plays a role, and the degree to which rheumatoid arthritis plays a role."
Rheumatoid arthritis is a chronic autoimmune disease marked by chronic inflammation of the lining of the joints. Over time, the disease can cause long-term joint damage, chronic pain, immobility and disability. About 2 million Americans have rheumatoid arthritis, according to the Arthritis Foundation.
According to the study, more than half a million patients have been treated with TNF-blocking antibodies, most of them because they have not responded to other treatments.
Two types of anti-TNF agents are currently licensed: infliximab (Remicade) and adalimumab (Humira). Both work by neutralizing TNF -- tumor necrosis factor -- a protein that's thought to play a major role in rheumatoid arthritis.
Both drugs are also known to pose an increased risk of serious infection, long noted as a warning on the drugs' package insert.
For this study, which appears in the May 17 issue of the Journal of the American Medical Association, the authors analyzed nine randomized, placebo-controlled trials of the two drugs. The trials involved close to 3,500 patients receiving anti-TNF antibody treatment and more than 1,500 controls receiving a placebo treatment.
Overall, patients taking one of the two TNF-based treatments had a 3.3 times higher risk of developing cancer and 2.2 times the risk of serious infection than patients taking the placebo. Malignancies were significantly more common in people receiving higher doses, compared with patients receiving lower doses of anti-TNF antibodies.
How big is the risk? According to the researchers, for one person to develop a cancer within six to 12 months, 154 people needed to be treated with either of the two drugs. Fifty-nine people needed to be treated for one person to develop a serious infection within three to 12 months, they said.
The reason for this drug-related increase in risk remains unclear. The drugs might interfere with the body's normal defenses against infection and against cancerous cells, the experts speculated.
But even if the drugs are responsible, the benefits may still outweigh the risks.
"Generally, if people are that bad, they can't function, and they are going to take the risk," Lindsey said.
"These are highly effective drugs," Matteson said. "They are drugs we want to continue to use. The overall functional capacity and even life expectancy of patients who have controlled rheumatoid arthritis is much better than if they have uncontrolled disease."
Matteson and his colleagues are hoping to use the same methodology to assess other medicines in their post-marketing phase. "This may give us a better idea of a signal of a more unusual problem, and we could get an idea about that early on rather than when the drug has been on the market for a long, long time," he said.
More information
To learn more about rheumatoid arthritis, visit the Arthritis Foundation.
