Test Assesses Response to RA Treatment

A biomarker test by Crescendo Bioscience could help doctors determine how patients will respond to treatments for rheumatoid arthritis. Three new studies on the biomarker blood test Vectra DA, found the test can predict patient responses to particular therapies. It can also show how patients could react to stopping therapy. In an interview with Rheumatology Network, Elena Hitraya, M.D., Ph.D., Chief Medical Officer of San Francisco-based Crescendo Bioscience, said a biomarker-based test can steer doctors toward the best and most cost-effective option. "Physicians always face a question of what is the best possible treatment option for patients," she said. Personalizing therapies In collaboration with Crescendo, which developed the test, researchers from Sweden conducted a prospective, observational study in which patients with rheumatoid arthritis who were methotrexate incomplete responders were randomized to receive biological therapy or the cheaper triple therapy of sulfasalazine, hydroxycholorquine and methotrexate.  A study published in the New England Journal of Medicine in 2013 found thattriple therapy is as effective as biological treatment in methotrexate incomplete responders. However, this similarity on the group level could mask subsets of patients who respond better to one drug or the other, Karen Hambardzumyan of The Karolinska Institute in Stockholm and colleagues reported on November 8 at the annual meeting of the American College of Rheumatology in San Francisco.  The researchers evaluated 157 methotrexate incomplete responders in the Swedish Farmacotherapy trial, measuring their multi-biomarker disease activity (MBDA) score from the Vectra DR test at the time of randomization to a treatment group. At the year one follow-up point, the researchers evaluated the clinical response in each group.  The MBDA scale is based on levels of twelve different cytokines, hormones and growth factors, and ranges from 1 to 100. Scores under 30 are considered low, Scores between 30 and 44 are moderate, and scores above 44 are high.  Patients with high MBDA scores responded better to anti-TNF inhibitor biological therapy than to triple therapy, the researchers found. Fifty-eight percent in this group responded to anti-TNF inhibitor drugs compared to a 35 percent response rate to triple therapy (p=0.04).  The low-MBDA group showed opposite results. Among these patients, 88 percent responded to triple therapy, while 18 percent responded to anti-TNF inhibitors (p=0.006).  The ideal cutoff appeared to be at a score of 38, the researchers found, with a highly significant difference between responses to the two options above and below this score. (p=0.001).   "This data indicates for patients in low disease activity, taking triple therapy provides better results," Hitraya said. "And for those patients who are in high disease activity, as measured by Vectra, they do much better on anti-TNF therapy."  Stopping treatments [[{"type":"media","view_mode":"media_crop","fid":"44635","attributes":{"alt":"©damerau/Shutterstock.com","class":"media-image media-image-right","id":"media_crop_9923731621820","media_crop_h":"0","media_crop_image_style":"-1","media_crop_instance":"5010","media_crop_rotate":"0","media_crop_scale_h":"0","media_crop_scale_w":"0","media_crop_w":"0","media_crop_x":"0","media_crop_y":"0","style":"font-size: 13.008px; line-height: 1.538em; float: right;","title":"©damerau/Shutterstock.com","typeof":"foaf:Image"}}]] The Vectra DA test can also predict the response of patients to tapering or stopping therapies, two additional studies found.  The first examined the likelihood of relapse in rheumatoid arthritis patients tapering disease modifying anti-rheumatic drug (DMARD) therapy. Using the Rheumatoid Arthritis in Ongoing Remission (RETRO) study, study leader Juergen Rech of the University of Erlangen-Nuremberg and colleagues gathered baseline MBDA scores in rheumatoid arthritis patients and compared these scores in patients who relapsed versus stayed in remission after being randomly assigned to taper DMARD treatment.  Moderate-to-high MBDA scores were twice as common in patients who relapsed compared to those who stayed in stable remission, the researchers reported at the ACR meeting on November 10. Fifty-eight percent of relapsing patients had moderate or high MBDA scores compared to 25 percent of patients who stayed in stable remission.  While MBDA scores independently predicted relapse versus remission, the reliability of the prediction increased when Vectra DA scores were combined with a test of anti-citrullinated protein antibody (ACPA) status. Combined, the two tests enabled the correct prediction of relapse in 80 percent of patients, the researchers found.  Another study found that Vectra DA scores can predict flares in rheumatoid arthritis patients who stop anti-TNF inhibitor therapy. Led by Femke Lamers-Karnebeek of Radboudumc in the Netherlands, researchers studied 439 rheumatoid arthritis patients randomly assigned to stop anti-TNF inhibitor treatment in the Dutch Potential Optimalisation of (Expediency) and Effectiveness of TNF-blockers (POET) trial. They found that within 12 months of tapering medication, 49.9 percent of patients had restarted their anti-TNF regimen, 59 percent had increased use of any medication and 57.2 percent had experienced at least one flare as reported by their doctors. Each of these outcomes was predicted by MBDA score at baseline, the researchers reported on November 10.  "Adjusted for baseline DAS28-ESR, disease duration, BMI and erosions, high MBDA scores (>44) were associated with an increased risk for TNFi re-initiation (OR=1.85, 95% CI 1.00–3.40), medication escalation (OR=1.99, 95% CI 1.01–3.94) and physician- reported flare (OR=2.00, 95% CI 1.06–3.77)," they wrote.  The three studies suggest new uses for the Vectra DA test, Hitraya said, though the test does not replace a physician's clinical assessment and understanding of patient comorbidities that might influence treatment choices, she said. Vectra DA is approved by Medicare for use twice a year. Approximately 40 percent of U.S. rheumatologists use the test, Hitraya said. Private coverage of the test varies by insurer. "We are actually in the process of planning a clinical utility study, prospective, that actually will provide data on both clinical utility on the test as well as looking at the economic endpoint," Hitraya said.   

References:

1. O'Dell, et al.

Therapies for Active Rheumatoid Arthritis after Methotrexate Failure.

N Engl J Med 2013; 369:307-318, July 25, 2013. DOI: 10.1056/NEJMoa1303006. 2. Hambardzumyan K, Bolce RJ, Saevarsdottir S, Forslind K, Karlsson JA, van Vollenhoven RF. The Multi-Biomarker Disease Activity Score in Methotrexate Incomplete Responders Predicts Clinical Responses to Non-Biological Versus Biological Therapy in Early RA [

abstract

]. Arthritis Rheumatol. 2015; 67 (suppl 10).  3. Rech J, Hueber AJ, Englbrecht M, Finzel S, Haschka J, Manger B, Kleyer A, Reiser M, Tony HP, Kleinert S, Feuchtenberger M, Fleck M, Manger K, Ochs W, Schmitt-Haendle M, Wendler J, Schuch F, Ronneberger M, Lorenz HM, Nüßlein H, Alten R, Cobra JF, Henes JC, Krüger K, Schett GA. Prediction of Disease Relapses By Multi-Biomarker Disease Test Activity in Rheumatoid Arthritis Patients Tapering DMARD Treatment [

abstract

]. Arthritis Rheumatol. 2015; 67 (suppl 10). 4. Lamers-Karnebeek F, Ghiti Moghadam M, Vonkeman HE, Tekstra J, Schilder A, Visser H, ten Klooster PM, Sasso EH, Chernoff D, Lems W, van Schaardenburg D, Landewé R, Van Albada I, Radstake TRDJ, van Riel P, van de Laar MAFJ, Jansen T. Multi-Biomarker Disease Activity Score As a Predictor of Flare in Patients with Rheumatoid Arthritis Who Stop TNF-Alpha-Inhibitor Therapy [

abstract

]. Arthritis Rheumatol. 2015; 67 (suppl 10).