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).
“This is particularly important as cardiovascular disease contributes significantly to the excess mortality in patients with RA,” says Dixon. However, he adds that the researchers were unable to determine whether the reduced risk of MI was specific to anti–TNF-α therapy or whether it would be seen with other therapies, as well.
The team had originally hypothesized that MIs would be reduced in all anti–TNF-α–treated patients with RA. “However, the finding that only responders have the added cardiovascular benefit fits with the paradigm of RA patients having increased cardiovascular burden acting via shared inflammatory mechanisms,” says Dixon.
Relaxation as RA Treatment
Another group of researchers suggest an added option in RA treatment – mindfulness-based stress reduction (MBSR).
In a recent issue of Arthritis Care & Research (2007;57:1134-1142), a team from the Center for Integrative Medicine at the University of Maryland School of Medicine in Baltimore found a 35% reduction in psychological distress and a significant improvement in well-being in RA patients who practiced MBSR for six months.
“Our findings are the first to indicate that the stress-reduction technique of meditation may prove valuable to patients in facing the emotional burden of this chronic disease,” says lead author Elizabeth K. Pradhan, PhD, assistant professor of family medicine.
With a group of 63 patients randomized to MBSR and control, the researchers found no differences between the groups following two months of MBSR. At six months, however, statistically significant benefits in psychological distress reduction and well-being were observed in the RA patients randomized to the MBSR group.
“It was surprising to us that, in this patient population, six months of mindfulness-based stress reduction practice were required to improve psychological distress and well-being significantly beyond the level found in the control group,” she says, adding that the control group showed initial improvement at two months, but returned to near baseline levels by study end.
“Our findings suggest that mindfulness-based stress reduction may be an effective complementary therapy for the management of RA,” she says.
Sue Pondrom is a medical journalist based in San Diego.