Rheumatoid Arthritis Drug Linked to Serious Infections and Cancers

A new meta-analysis of many previous studies of TNF- (tumor necrosis factor) blocking antibodies for treatment of rheumatoid arthritis has confirmed a previously discovered increased risk for serious infection and has found that cancer also is a potential risk associated with the drugs.

"This study shows a strong association between treatment with TNF-blocking antibodies and the development of serious infections, such as pneumonia, and cancers," says Eric Matteson, M.D., Mayo Clinic rheumatologist and a senior study investigator. "It's a very serious issue. TNF-blocking antibodies are effective for treatment for rheumatoid arthritis and related conditions, but patients and health care providers must know that there is an increased risk for these complications and be alert for them."

More than half a million patients have received therapy with TNF-blocking antibodies. Patients treated with these drugs usually have not had favorable results with other drug treatments for rheumatoid arthritis or have more severe disease, according to Dr. Matteson. The drugs also are used to treat psoriasis, Crohn's disease and other conditions.

The study involved a systematic literature search for trials of TNF-blocking antibodies for rheumatoid arthritis. In addition, the researchers searched for such trials in the abstract databases of the scientific meetings of the American College of Rheumatology and the European League Against Rheumatism through December 2005 and conducted interviews with the manufacturers of the two licensed TNF-blocking antibodies, infliximab and adalimumab. The investigators found nine trials that met their inclusion criteria, including 3,493 patients who received TNF-blocking antibodies and 1,512 patients who received placebo. They gathered all data related to serious infections and malignancies in the studies' participants. Collectively, using various types of analyses, the researchers found that those treated with TNF-blocking antibodies had 3.3 times the risk of developing cancer than those given placebo, and 2.2 times the risk of serious infection. Cancers were much more common in those patients treated with high doses of TNF-blocking antibodies.

Dr. Matteson explains that TNF-blocking antibodies might be connected with an increased risk for infection and malignancies because the drugs interfere with immunological mechanisms critical to fighting infection and the body's normal function in surveying itself for cancerous cells.

The risk patients undertake when receiving TNF-blocking antibody treatment is "moderate," according to Dr. Matteson. He explains that, on average, rheumatoid arthritis patients are already at twice the risk of serious infections as others, and that taking TNF-blocking antibodies increases that risk.

The decision whether to have TNF-blocking antibody therapy for rheumatoid arthritis must be made by each patient and physician, according to Dr. Matteson. He continues to use this therapy for some patients, he says.