Frederick Wolfe, MD, director of the National Data Bank for Rheumatic Diseases in Wichita, Kansas, points out another factor that makes it difficult to neatly tie together lymphoma and TNF inhibitors. "If you have severe RA, you are more likely to be prescribed a biologic, but you are also more likely to get lymphoma because of the severity of your disease whether or not you get the biologic," he notes. "It's difficult to disentangle the effect."

To tangle matters even more, lymphomas are relatively rare, so researchers must study large numbers of RA patients in order to find enough lymphoma cases to draw meaningful conclusions. But RA itself, although the second most common arthritis diagnosis, is fairly rare, occurring in only one percent of the general population.

With those caveats in mind, consider the results of recent studies, which shift the blame away from treatments and suggest that keeping RA in check should be your biggest concern.

In research published in Arthritis and Rheumatism, investigators at Harvard Medical School and the University of British Columbia pooled medical databases from Pennsylvania, New Jersey and British Columbia to compare cancer rates between patients using the older disease-modifying anti-rheumatic drug (DMARD) methotrexate and those using a newer, biologic drug such as a TNF-inhibitor. The conclusion? Users of biologic agents are no more likely than users of methotrexate to develop cancer. Similarly, a study of 19,562 patients led by Dr. Wolfe and his colleague, Kaleb Michaud, PhD, showed no evidence for an increase in lymphoma incidence in those on TNF inhibitors.

In another investigation, also published in Arthritis & Rheumatism, Swedish researchers mined a national registry of nearly 75,000 RA patients and analyzed medical records and case histories of a subset of 378 RA patients who had developed lymphoma between 1964 and 1995 and 378 lymphoma-free patients. They found a dramatic association between lymphoma and disease activity, which is determined by currently swollen or tender joints, increased levels of inflammatory markers and X-ray evidence of erosion in at least one joint.

Compared with patients with low RA activity, those with medium disease activity showed an eight-fold increase in the likelihood of developing lymphoma. For those with high activity, the probability took a staggering 70-fold jump, leading the authors to conclude that with aggressive treatment to suppress the disease activity of rheumatoid arthritis, lymphoma risk might actually be reduced.

As for other cancers, Dr. Wolfe and Michaud studied 13,000 patients participating in a research project between 1998 and 2005, looking specifically at links between treatment with a biologic agent and cancer risk. They found that biologic therapy doubled the odds of developing skin cancers, including melanoma, but did not put patients at greater risk for lymphoma, breast, lung, colon or any other cancer.

"These increased risks that we identify and report are extremely small," Dr. Wolfe stresses. "Melanoma is serious but not common; most other skin cancers are not serious. I don't think anyone should be concerned."

Weighing all the evidence about the rheumatoid arthritis–cancer connection, Dr. Furst offers this advice to patients: "Rheumatoid arthritis is a very serious disease, and overall, the therapeutic benefits of the drugs used to treat it far outweighs their downsides. The risk from not doing anything to contain the disease is much greater."