Do Side Effects of Anti–TNF-α Therapy Warrant Reconsideration?
While healthcare providers appreciate the benefits of biologic therapy for RA, concerns continue that this relatively new treatment may convey an inordinate risk of serious infection and malignancy. The issue is confused by the fact that RA itself increases the risk of some cancers and infection. Three recent articles in Arthritis & Rheumatism addressed these issues with reassuring findings – and a caveat.
The first study examined the incidence of cancer over a seven-year period among 13,001 RA patients in an observational database (2007;56:2886-2895). In the patients who received biologic therapy, they found a slight increased risk for nonmelanotic skin cancer and melanoma, but not for solid tumors or lymphoproliferative malignancies.
Lead author Frederick Wolfe, MD, of the director of the National Data Bank for Rheumatic Diseases, says the current study verifies and extends previous studies into the biologic era. “Similar studies that were larger than ours found an increase in cancer, but within the same range that we did – zero to a slight increase,” he says.
While there is no indication that rheumatologists should discontinue anti–TNF-α therapy because of malignancy risk, a study limitation is that cancer takes a long time to develop. “Smoking-associated cancers take decades and biologic therapies haven’t been used for a long period of time, so this doesn’t clear them,”says Dr. Wolfe.
Encouraging news on the risk of serious infection was conveyed in a separate paper by researchers from the British Society for Rheumatology (BSR) Biologics Register Control Centre Consortium and the BSR Biologics Register (2007;56:2896-2904).
In an observational study of 10,755 patients, researchers found no overall increased risk of serious infection in patients treated with anti–TNF-α therapy. “However, this single estimate hid a four-fold increased risk of all-site serious infection within the first 90 days’ treatment,” says lead author W.G. Dixon, a clinical research fellow for the BSR Biologics Register.
In their conclusion, the paper’s authors note that “there may be important increases in true risk, notably early in the course of treatment, that would become more evident depending on the definition of at-risk period.”
Dixon says the findings illustrate the strengths and limitations of large observational studies in “real life” settings, including when adverse events should be attributed to a particular drug and how selection factors may influence results.
In another observational study by the BSR group, patients who have a response to anti–TNF-α therapy in their joints were also found to have a reduced incidence of myocardial infarction (MI) (2007;56:2905-2912).