MARINA DEL REY, CALIF. — Like rheumatologists everywhere, Dr. Joan M. Bathon, director of the Johns Hopkins Arthritis Center, sometimes has to rely on clinical trial and error to find the right medications for her patients.
It would be a tremendous help to be able to predict treatment response, and ways to do that may be coming to the clinic in the not-too-distant future, she said at rheumatology seminar sponsored by the University of California, Los Angeles.
Dr. Bathon said she usually starts RA patients on methotrexate. It generally takes 2-4 months to tell if the drug is working.
If methotrexate fails to bring RA under full control, Dr. Bathon said she will add a second agent. If a low to moderate level of disease activity remains, she'll add sulfasalazine, leflunomide, or hydroxychloroquine, depending on patient preference. With more severe residual disease activity, she's likely to add a tumor necrosis factor (TNF) inhibitor.
If one TNF inhibitor doesn't work, she'll try another. If the patient fails two TNF therapies, abatacept or rituximab are the next options, although rituximab is being used more cautiously these days since being linked with progressive multifocal leukoencephalopathy, she said.
Tocilizumab (Actemra)—which was approved by the Food and Drug Administration earlier this year as the first interleukin-6 receptor-inhibiting monoclonal antibody—is also an option if TNF inhibitors fail. The rheumatology community is still figuring out its place in the treatment paradigm, she said.
Research into biomarkers to predict treatment response may make that possible, Dr. Bathon said during her presentation.
While biomarkers for disease progression, treatment toxicity, and other aspects of RA care are also being sought, the biggest efforts are going into finding biomarkers for treatment response, according to Dr. Bathon.
Knowing, for instance, the particular molecular pathway—TNF, B cell, or T cell—that is most active in an individual RA patient would indicate if that patient would benefit from a TNF inhibitor such as etanercept, a B-cell depleter such as rituximab, or some other therapy.
Research into biomarkers for TNF inhibitor response is particularly active.
One study recently found that polymorphism in a TNF-alpha promoter gene (-308 G greater than A SNP) is associated with higher serum levels of TNF-alpha in RA patients, suggesting that the polymorphism is a weak predictor of response to anti-TNF therapy (Rheumatology Reports 2009 [doi:10.4081/rr.2009.e1]).
“If you have this, a TNF [inhibitor] may be the drug of choice,” Dr. Bathon said.
Another recent study measured an array of autoantibodies and cytokines in 93 patients from three different ethnic groups. A 24-biomarker signature was discovered that predicted good to excellent response, as well as lack of response, to etanercept (Arthritis Res. Ther. 2009;11:115).
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