Early detection and aggressive treatment of rheumatoid arthritis (RA) are vital to prevent joint damage. To spot RA and measure its progression, rheumatologists test the blood for certain biomarkers that are characteristic of RA. Although several biomarker tests – the erythrocyte sedimentation (sed) rate, the C-reactive protein (CRP), and rheumatoid factor (RF) – indicate inflammation, they are fairly non-specific to RA. So, the development of more specific biomarker tests is important. These tests allow earlier detection of RA and also pave the way for more customized care.
Below are descriptions of more specific biomarker tests that are being used to diagnose and monitor RA disease activity.
Polyglutamate Testing: Measuring Methotrexate’s Effectiveness
What It Is: Methotrexate is one of the most commonly prescribed and effective drugs for RA. Once it enters the cells, it is converted to methotrexate polyglutamates, explains rheumatologist Maria I. Danila, MD, assistant professor of medicine at the University of Alabama at Birmingham.
Unless that conversion occurs, methotrexate won’t work its therapeutic magic. Because 30–40% of patients do not respond to methotrexate, the measurement of methotrexate polyglutamates in the blood may show if a person if being adequately or inadequately treated. The measurement is taken three months after someone begins taking methotrexate.
Why It’s Different: It can take months for methotrexate to have an effect on how you feel. The theory is that measuring methotrexate polyglutamate levels at three months may indicate earlier whether the methotrexate is working.
What It Means for Personalized Medicine. Measuring methotrexate polyglutamate levels may allow a doctor to adjust methotrexate doses to raise or lower the polyglutamate levels in each patient until it reaches a therapeutic level – or change the medication choice altogether.
Vectra DA: A Multi-Biomarker Test
What It Is: Vectra DA is a blood test that measures 12 biomarkers of RA. The test is not used to diagnose RA but to monitor disease activity and to help predict joint damage.
Why It’s Different: It’s the first test that measures multiple biomarkers for RA at once. “It reveals disease activity in a way that correlates with the way we usually measure it,” says Jeffrey Curtis, MD, professor of medicine at the University of Alabama at Birmingham and a scientific advisory board member of Crescendo Bioscience, the manufacturer of Vectra DA. “It also does a pretty good job of predicting joint damage and flares that correlates with ultrasound and MRIs [magnetic resonance imaging].”
What It Means for Personalized Medicine. “It’s one more piece of information that a doctor can use to optimize the care of an RA patient,” says Dr. Curtis. He also stresses that not everyone who has RA needs the test: “It’s only needed when there is uncertainty about how active the RA is or if the doctor is unsure whether to make a change in treatment.”
Anti-CCP2 Test: More Accuracy
What It Is: This is the second generation of the first anti-CCP test, which has been around since the late 1990s, says John Griffiths, founder and CEO of Gold Standard Diagnostics, the manufacturer of the test. Antibodies of cyclic citrullinated peptides (CCP) are often present in the early stages of RA, even before clinical signs of RA appear.
Why It’s Different: The second generation test was developed by selecting the CCPs that best detected RA, making it a more sensitive and specific test than the first generation.
What It Means for Personalized Medicine: Although the test doesn’t have much impact on personalized medicine, it is an additional tool in the diagnosis and management of patients with RA.
Anti-MCV: Looking for Antibodies Common in Early RA
What It Is: This blood test checks for antibodies to mutated citrullinated vimentin, or MCV. MCV is a protein “that drives RA,” says Martin Fleck, MD, chief physician of the clinic for rheumatology and clinical immunology for the Asklepios Clinic in Bad Abbach, who has been involved in the research of anti-MCV.
Why It’s Different: “MCV antibodies are highly specific and may be detectable several years before the RA [is clinically obvious],” says Dr. Fleck. “You won’t find these antibodies in healthy people.” He notes that the MCV test is a better predictor of aggressive disease or erosions than the anti-CCP test. Because the CCP test and MCV test measure different antibodies, both tests are given along with a test for rheumatoid factor.
What It Means for Personalized Medicine: “The MCV test extends the repertoire of biomarkers for RA,” says Dr. Fleck. “And the [quick version] helps identify immediately RA patients among patients presenting with [other forms of] arthritis.”