Early detection and aggressive treatment of rheumatoid arthritis are vital in order to prevent damage to joints. To spot RA and measure its progression, rheumatologists test the blood for certain biomarkers, or biological substances – proteins, for instance – that are characteristic of RA. Although several biomarker tests – the erythrocyte sedimentation (sed) rate, the C-reactive protein (CRP), and rheumatoid factor (RF) – indicate inflammatory activity, they are fairly non-specific to RA. In other words, the tests could be positive if you have an infection or another cause for inflammation besides RA. So, the development of new biomarker tests specific to RA is important.These tests may not only allow earlier detection of RA but they also represent an advance in personalized medicine: The more specific the test, the more customized care becomes for each RA patient.

As rheumatologist Jeffrey Curtis, MD, MS, MPH, associate professor of Medicine at the University of Alabama-Birmingham and a consultant for Crescendo Bioscience, the manufacturer of Vectra DA, a new test, says, “The desire is to measure biomarkers of RA beyond [the sed rate and the CRP] that do a better job of knowing how active the RA is.”

Below are descriptions of new and emerging biomarker tests that are being used to diagnose and monitor RA disease activity

Polyglutamate Testing: A Measure of Methotrexate’s Effectiveness

What It Is: Methotrexate is one of the most commonly prescribed and effective drugs for rheumatoid arthritis. Once it enters the cells, it is converted to methotrexate polyglutamates, explains Maria I. Danila, MD, MSc, assistant professor of Medicine, Division of Clinical Immunology and Rheumatology at the University of Alabama-Birmingham.

Unless that conversion occurs, methotrexate won’t work its therapeutic magic. Because 30 to 40 percent of patients do not respond to methotrexate, and early treatment of RA is essential, 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 work its effect, results largely gathered through a doctor’s assessment, a swollen joint count and a disease activity score. 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. But more research is needed, says Susan M. Goodman, MD, a rheumatologist at the Hospital for Special Surgery in New York City.

“There is significant overlap between polyglutamate levels in patients who have responded to methotrexate and those who haven’t, so standards would be difficult to define. And it takes months for methotrexate polyglutamate levels to reach a steady state, which lessens the usefulness in using the levels to guide therapy,” she says.

Vectra DA: A New Multi-Biomarker Test

What It Is. Vectra DA is a blood test that measures 12 biomarkers of RA. “Researchers began with 396 biomarkers and winnowed those down to the 12 that have the strongest and most consistent relationship with the disease activity of rheumatoid arthritis,” says Dr. Curtis. Some of the biomarkers include those that are of part of typical RA labwork such as c-reactive protein (CRP); interleukin 6, a driver of RA inflammation, and tumor necrosis factor, type 1 (TNF-R1), a chemical also involved in RA inflammation.  Vectra DA 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 Dr. Curtis. “It also does a pretty good job of predicting joint damage and flares that correlates with ultrasound and MRIs [magnetic resonance imaging].”

Dr. Curtis 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.”

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 notes that while not every doctor has ready access to ultrasound or MRI equipment, this test requires a blood draw only, so it’s a more accessible test and may help predict joint damage as well.

Anti-CCP2 Test: A New Kit with More Accuracy

What It Is. This test, available since October 2011, is the second generation, or second incarnation, 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), or proteins, are often present in the early stages of RA, even before clinical signs of RA appear. The second generation test was developed by screening CCPs from the blood of RA patients, selecting from those only the CCPs that best detected RA so that it’s a more sensitive and specific test than the first generation test.

Why It’s Different. “It uses basically the same testing method as the first anti-CCP test,” says Griffiths. But the new kit has a higher percentage of sensitivity than the older version because it has more narrowly selected the CCPs that are most sensitive and specific to RA.

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 (Mutated Citrullinated Vimentin): A Simple Blood Test Looking for Antibodies Common in Early RA

What It Is. This simple blood test checks for antibodies to mutated citrullinated vimentin, or MCV. MCV is a protein “that drives RA,” says Martin Fleck, MD, a researcher and teacher at the University of Regensburg, Germany, and 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. “But if the test is negative, RA is not excluded,” he says. It’s negative in approximately 20 to 30 percent of RA patients.

Because the CCP test and MCV test measure different antibodies, both tests are given along with a test for rheumatoid factor.

One version of the MCV test, Rheuma Check, is simple, requiring no lab equipment. A few drops of blood are placed on a test strip, revealing the presence of the MCV antibodies within 15 minutes. A more accurate version of the test that determines the exact concentration of MCV antibodies takes two hours to process. “The result is usually available the next day,” says Dr. Fleck.

What It Means for Personalized Medicine. “The MCV test extends the repertoire of biomarkers for RA,” says Dr. Fleck. “And the Rheuma Check helps identify immediately RA patients among patients presenting with [other forms of] arthritis.”