Investigators have identified a biomarker that could help doctors select patients with rheumatoid arthritis who will benefit from therapy with drugs such as Enbrel, a tumor necrosis factor (TNF)-antagonist drug. The study, led by researchers at Hospital for Special Surgery in collaboration with rheumatologists at University of Southern California, appears in the February issue of the journal Arthritis & Rheumatism.
"While our study was performed on a relatively small group of patients and will need to be confirmed in a larger cohort, the data are promising and may be clinically significant for the medical management of patients," said Mary K. Crow, M.D., director of Rheumatology Research and co-director of the Mary Kirkland Center for Lupus Research at Hospital for Special Surgery. "Treatment with these drugs is very expensive; the drugs can cost around $16,000 or so per year. If you are going to use them, you would like to know that they are likely to work in your patient." Other well-known TNF-antagonists include Humira and Remicade.
While TNF antagonists have brought relief to thousands of people with rheumatoid arthritis, the drugs are not highly effective in 30 percent to 50 percent of patients. Clinicians thus run the risk of providing a therapy to patients that doesn't work well, is expensive and is potentially toxic. Patients taking TNF antagonists, which have been available for roughly ten years, can run the risk of developing bacterial or fungal infections.
While studies have identified factors associated with poor response to these drugs such as expression of certain genes, none of the factors has as yet provided doctors with a tool that will help select patients who are likely to respond to the drugs or identify those less likely to respond. Investigators at HSS hoped to remedy this and turned their attention to the type I interferon proteins, specifically a type called interferon beta (IFN-beta). Previous studies have revealed that levels of IFN-beta, a protein that can limit cell division, is present in the joint tissue of some patients with rheumatoid arthritis. The researchers wondered if variable levels of this protein could play a role in how patients respond to TNF-antagonist drugs. To test this hypothesis, the investigators set out to determine the relationship between levels of type I interferon activity in the blood prior to beginning therapy and the ability of the drug to control rheumatoid arthritis in patients. They studied the role of IFN-beta, and because they knew that IFN-beta induces interleukin-1 receptor antagonist (IL-1Ra), another protein, they also tested levels of IL-1Ra.