NEW YORK (360Dx) – Researchers from Myriad Genetics subsidiary Crescendo Bioscience and their collaborators have published a study in Rheumatology detailing a version of the firm's Vectra DA test for rheumatoid arthritis adjusted to account for patient age and adiposity.
The updated version of the test, which the company has been offering since the end of 2017, improves its performance in patients with either very high or very low levels of adiposity, said Elena Hitraya, chief medical officer at Crescendo.
Crescendo collaborators also recently published a study in The Journal of Rheumatology looking at the clinical use of Vectra DA among US rheumatologists. Hitraya said that the study, which found that patients with moderate and high Vectra DA scores were more likely than those with low scores to have their therapies adjusted following testing, had been key to convincing Medicare contractor Palmetto GBA to reject the draft local coverage determination it issued in late 2016 proposing Medicare end coverage of the test. Myriad President and CEO Mark Capone noted on a conference call in August following release of the company's fiscal Q4 2018 earnings results that Medicare had "formally removed the draft non-coverage LCD from their website."
Vectra DA measures the levels of 12 proteins in patient serum to provide a disease activity score for rheumatoid arthritis patients that can help doctors predict the likelihood that a patient will see worsening of their disease as assessed by measures like radiographic progression.
Hitraya noted that the company has tested more than 325,000 patients and said that as its collection of patient data grew, it observed that Vectra DA scores were higher in women than men and went up with increasing age, leptin concentration, and body mass index. These observations dovetailed with a growing clinical literature on the role of obesity in inflammation, she said, and this combination led Crescendo to explore whether adjusting for age and adiposity might improve the test's performance.
In the Rheumatology study the researchers developed two models that adjusted the Vectra DA score for age, sex, and adiposity — one that used BMI as a proxy for adiposity and one that used serum leptin concentration. They developed the models using a cohort of 325,781 rheumatoid arthritis patients who had received Vectra DA testing and for whom data on age, sex, and serum leptin levels were available. They also used an additional 1,411 patients from five studies of the test where patient BMI was collected to develop the BMI-based adjusted model.
They found that the leptin-based adjusted score more closely correlated with radiographic progression than either the BMI-based adjusted score or the non-adjusted score. Reanalyzing the 325,781 cohort with the leptin-adjusted score, the researchers found that 90 percent of patients would have seen a change from their original score of between -9 and +11 points (Vectra DA is scored on a one to 100 scale).
Among patients who scored low with the original Vectra DA test, 24 percent were reclassified as having moderate disease activity, while 9 percent and 12 percent of moderate patients were reclassified as low and high, respectively, and 21 percent of high patients were moved to the moderate category.
The authors noted that the largest changes from the original score were in cases where "age and leptin concentrations are both very high or very low."
Looking at the adjusted test's ability to predict radiographic progression in rheumatoid arthritis patients the researchers found that among low, moderate, and high scoring patients, 1.1 percent, 3.9 percent, and 9.3 percent, respectively, showed radiographic progression, demonstrating that risk of radiographic progression rose with test score.
The roughly 9 percent of high-scoring patients who showed progression is substantially lower than found in previous studies of Vectra DA. For instance, in a meta-analysis of six previous studies Crescendo published last year at the European League Against Rheumatism (EULAR) annual meeting, the company found that between 20 percent and 30 percent of patients with a high Vectra DA score showed radiographic progression within a year.
Vectra DA's relationship to radiographic progression has proved a point of contention in the past and was among the factors that led Palmetto to issue its draft local coverage decision proposing an end to Medicare coverage in 2016.
Crescendo has been working since the issuance of that draft decision to address Palmetto's concerns, which also included the lack of clinical utility data supporting the test.
In November, researchers funded in part by Crescendo published the Journal of Rheumatology study, which investigated doctor ordering patterns and how the Vectra DA score was linked to changes in patient treatment regimens. Using Medicare data from 60,596 rheumatoid arthritis patients tested with Vectra DA between 2011 and 2015, the researchers found that patients with high scores and moderate scores were 2.6 and 1.5-fold more likely to change therapy within six months of testing, though, as the authors note, the data don't "provide certainty that the main reasons that clinicians switched therapy was the [Vectra DA] result."
The study also provided some insight into usage rates of the test. Between 2011 and 2015, roughly 125,000 tests were ordered for roughly 75,000 patients, and in 2015, 1,426 rheumatologists with at least one rheumatoid arthritis patient ordered at least one test, which represented 25 percent of rheumatologists identified by Medicare as caring for patients with the condition.
Upon announcing the company's $270 million purchase of Crescendo in February of 2014, then Myriad President and CEO Peter Meldrum said Vectra DA was on a revenue run rate of $10 million per quarter "and growing rapidly."
Since then, revenues from the test have continued to rise, but not to the levels originally anticipated by the company, which gave an initial 2014 guidance of $65 million in sales. In fiscal year 2018, Crescendo posted $57.2 million in Vectra DA sales, up from $43.7 million in 2017, and $47.8 million in 2016.