The Need for Better Diagnostic and Individualized Tests for RA
There are several blood tests that rheumatologists currently use to diagnose and monitor rheumatoid arthritis disease activity. Rheumatoid factor (RF) is an antibody identified with RA and other autoimmune diseases. A newer test specific to RA called anti-cyclic citrullinated peptide, or anti-CCP, has been found to have more predictive value than rheumatoid factor tests.1 Since RA involves inflammation, general tests of systemic inflammation including erythrocyte sedimentation rate (ESR) and c-reactive protein may be used. These tests are not specific to RA and are used for a variety of diseases and conditions. But these tests are not completely accurate and they may fail to identify disease activity.
The blood-markers for RA
In one study of thousands of RA patients, it was found that between 35-45% of patients showed normal rheumatoid factor (RF), ESR, or c-reaction protein blood tests.2 That is a large proportion of people who display the damaging symptoms of RA but did not have positive blood test results. I am a case in point. For several years I never showed a positive blood test of any kind yet displayed serious symptoms and joint damage resulting in several surgeries. Only sometime later did I display positive RF and c-reactive protein tests. Fortunately, my rheumatologist understood the problem with these tests and proceeded to diagnose and treat in spite of the results. Clearly, better tests are drastically needed.
While attending the recent American College of Rheumatology3 conference in San Diego, I spent considerable time attending sessions related to risk factors and blood markers for RA. There were many presentations related to all sorts of blood markers including anti-CCP and other novel proteins with exotic names such as citrate CLYBL, serum ImG free light chains, and anti-CarP. At one presentation, a researcher mentioned that finding an accurate and useful blood test for RA is the “Holy Grail” of research. According to an article published by a group of researchers from the Netherlands, “The development of biomarker-based disease activity scores might allow easy and frequent monitoring of patients to rapidly adjust treatment.”4
While we wait for accurate, reliable, and predictive blood tests for RA, there are several tests on the market or in development that hold therapeutic promise. A company called Crescendo Bioscience5 developed and markets a test called Vectra-DA6. The test provides results about 12 proteins7 that are related to RA processes and is designed to gauge the level of disease activity. It technically is not designed to make therapeutic decisions about treatments as according to Crescendo’s website8, “Vectra DA has not been studied for use in predicting which specific therapy or class of therapy will work for you.” But a RA patient recently told me that she did not respond well to anti-TNF biological treatments. She took the Vectra-DA test and it showed that her interleukin-6 (IL-6) levels were high. Her rheumatologist switched her to Actemra (tocilizumab) that is a biological targeting IL-6. She told me that she had a swift and positive response to Actemra. Vectra-DA is not yet typically covered by insurance and the company offers financial assistance9.
New tests for diagnosing RA?
A company called Prometheus Labs10 developed two bloods tests called Anser11 which are related to the effectiveness of anti-TNF biologicals in inflammatory bowel disease (IBD). Anser ADA is designed to measure blood levels of Remicade and antibodies to Remicade while Anser IFX is designed to measure blood levels of Humira and antibodies to Humira. The test results are given to doctors in a report (see sample) that shows how much of the drug is present in the patient’s blood along with a measure of antibodies to the drug. Such results can be helpful in making a determination about continuing with a biological medicine. But these tests are limited for use only in IBD cases and not for other autoimmune diseases like RA that is also treated with Remicade and Humira. It is not evident that this company is seeking to develop similar tests for RA. Such a test would be helpful since a large proportion of RA patients either fail to show an initial response or lose a response to a biological over time.
I was fortunate to have a conference call with researchers from a biotech company called Selventa12. Their goal is to use genetic data to predict an individual patient’s response to RA biological drugs. They are working on a test called ClarifyRA13. Their stated goal for the test is to “…identify likely responders and non-responders to all marketed and investigational therapeutic options based on the mechanistic insight of individual patient’s RA biology.” Such a test would be very beneficial when making treatment choices and could save the patient valuable time and money since such a large proportion of patients fail to respond to treatments. This test is still in the proof of concept phase and they hope to expand their work to large datasets in the future.
The notion of P4 medicine14, a term coined by renowned genetic scientist Dr. Leroy Hood, refers to the future of medicine where individual genetics are used to help Predict and Prevent disease. This will result in medical care that is Personalized and Participatory. P4 medicine may become a reality when the intersection between an individual’s genetics and predicted treatment efficacy proposed by Selventa’s model is realized. Perhaps, in the future, more individualized tests for RA will help P4 medicine become a reality. More research is clearly needed to help diagnose RA and to make treatment decisions for individual patients.
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