The link between rheumatoid arthritis (RA), a chronic, systemic, inflammatory, autoimmune disease and the incidence of cancer is still murky. Multiple epidemiologic studies have shown that hematopoietic (blood), lung, and skin cancers are increased in incidence in RA patients, while breast and colon cancers are decreased.

Whether these cancer rates are caused by RA itself, the immunosuppressive chemotherapeutic agents used to treat RA, or by newer biologic therapies is an issue of ongoing investigation.

Conflicting findings particularly exist over the risk of malignancy related to the use of tumor necrosis factor alpha (TNFα) blockers, biologic therapies shown to be extremely effective at controlling the progression of RA in patients who do not respond to traditional disease-modifying anti-rheumatic drugs (DMARDs).

A recent study again examined the risk of cancer among biologic-treated RA patients. The researchers examined the extensive databases of both the National Data Bank for Rheumatic Diseases as well as the US National Cancer Institute SEER (Surveillance, Epidemiology, and End-Results).

The scientists studied the incidence of cancer in 13,001 RA patients, over 49,000 years. Nearly half of these patients, 49 percent, had a history of exposure to anti-TNFα drugs.

They found that biologic treatment of RA increases a patient's risk of skin cancers, including melanoma, but not any other specific cancers such as lung, liver, brain, or bone cancers. And there was no increased incidence of other malignancies such as Hodgkin's disease, non-Hodgkin's lymphoma or leukemia.

Among the study population, the investigators found 623 cases of skin cancer and 537 cases of other cancers. They then determined the effect of biologic drug use on cancer occurrence. As an estimate of the relative risk of developing different types of cancer, the authors calculated the odds ratio for every cancer affecting the subjects, performing statistical techniques to reduce the effect of variations in treatment duration.

They also controlled for the variables of gender, smoking history, education level, disease severity, and baseline use of prednisone. In addition to assessing the risk of various cancers associated with biologic treatment in general, the researchers extended the analyses to individual TNFα blockers, etanercept (Enbrel) and infliximab (Remicade).

They found anti-TNFα therapy was linked to an increased risk of skin cancers, including melanoma. The odds ratio for developing melanoma was 2.3. Biologic use had no impact on any other type of cancer. The overall risk for all malignancies was 1.0. (A measure of 1.0 indicates that there is no overall risk for cancers in general, while the risk of 2.3 for melanoma indicates that a given person is 2.3 times more likely to develop a melanoma if they are taking a biologic than if they weren't).

The authors stated, "Although our data do not show associations between malignancy and biologic therapy, except for skin cancers, the mean and median exposure to biologics was only 3.0 years. IIt is possible that with increasing time of follow up or of exposure, the association between malignancy and biologic therapy would become stronger. However, true associations are regularly seen within this time frame."

Despite its limitations, this study offers some reassurance to RA patients. The study validates the fact that for cancers in general, including lymphoma, that there is no significant increased risk for biologic users. The only cancer where there is a signal- in this study- is for skin cancers and melanoma.

(Wolfe F, Michaud K. Biologic Treatment of Rheumatoid Arthritis and the Risk of Malignancy: Analyses From a Large US Observational Study. Arth Rheum 2007; 56: 2886- 2895)