Makers of Test That Predicts RA Progression Present Results, Gain Foothold Among Clinicians

Crescendo Bioscience, creators of the Vectra DA blood test to predict the progression of rheumatoid arthritis (RA), is gaining market share in the United States, with its new parent company, Myriad Genetics, reporting that 25% of the nation’s rheumatologists are now using the test compared with 15% a year ago.¹

The increased use of Vectra DA comes amid a flurry of activity for Crescendo during 2014, which began with Myriad’s purchase of Crescendo for $270 million² and continued with the publication of results on the test’s effectiveness and clinical utility, including a landmark study from Sweden that appeared in Annals of Rheumatic Diseases.³

Results compare how well the test predicts radiologic progression (RP), which is an assessment performed by observing scans of the hands and feet of persons with RA and scoring the level of damage after a period of time, often 1 year. The most common scoring uses the van der Heijde-modified Sharp scale, which was used in the study in Sweden.^3,4 (In prior years, RA was sometimes not diagnosed until radiologic progression was observed, but the goal today is to avoid damage. See page SP429.)

RP is associated with an increase in inflammation and physical symptoms, including pain and loss of mobility,⁴ and is often used as an end point in clinical trials to gauge the effectiveness of new medications to treat RA, including many new biologics. Crescendo’s promotion of Vectra DA asserts that the test helps guide rheumatologists in how aggressively to treat patients, and may identify candidates for clinical trials.⁵

SWEFOT Trial. The Sweden Farmacotherapy (SWEFOT) trial involved 235 patients with early RA.³ Patients at baseline, who had not received any disease-modifying RA drugs, received both radiography and baseline screenings, including the Vectra DA blood test, which measures multiple-biomarker disease activity (MBDA). The MBDA score, which ranges from 1 to 100, is based on serum levels of 12 key biomarkers: the adhesion molecule VCAM-1, growth factors EGF and VEGF-A, cytokines/receptors IL-6 and TNFR, matrix metalloproteinases MMP-1 and MMP-3, skeletal-related protein YKL-40, hormones leptin and resistin, and acute phase proteins SAA and CRP.⁶

Among the 235 patients, 5 had low MBDA scores at baseline and 29 had moderate scores. Of this group, none of the patients with low scores and only 1 patient in the moderate group had RP after a year. Meanwhile, the share of patients who had both a high MBDA score at baseline and showed RP at 1 year was 20.9%. MBDA scores were better predictors of RP than other measures used, such as the C-reactive protein (CRP) test and erythrocyte sedimentation rate (DAS28-ESR).

The study, which appeared May 8, 2014, included the finding that with early RA, “MBDA score at baseline was a strong independent predictor of 1-year RP. These results suggest that when choosing initial treatment…the MBDA test may be clinically useful in identifying a subgroup of patients at low risk of RP.”³

Results Presented at EULAR. Vectra DA was featured in 8 poster presentations in June at the European League Against Rheumatism (EULAR) Congress held in Paris.⁵ Some presentations followed up results from the May SWEFOT study, while others explored the test’s ability to detect inflammation among patients who appeared to be in remission. Among the results presented:

Karen Hambardzumyan, MS, research assistant, Karolinska Institute, Stockholm, Sweden, and lead author of the May article,³ presented results showing that the predictive value of Vectra DA held up over a 2-year period. Researchers assessed whether MBDA scores at 3 and 12 months to determine if a change of MBDA category, due to treatment, predicted subsequent RP at the 2-year mark. “At all measured time points, a low MBDA score or achievement of the latter was associated with low risk for subsequent X-ray progression,” the authors found.⁷

Hambardzumyan also presented results on patients who did not initially respond to methotrexate, the first-line treatment for almost all RA patients. This project evaluated whether the change in MBDA score during methotrexate therapy could predict later response to triple therapy or biological therapy. Among early RA patients who did not achieve low disease activity on methotrexate, patients with the greatest decreases in MBDA score were more likely to respond to triple therapy, while those with smaller score decreases were more likely to respond to anti-TNF (tumor necrosis factor) therapy.⁸

Margaret H. Ma, locum consultant rheumatologist, King’s College NHS Trust, presented results showing that the Vectra DA score is associated with power Doppler ultrasound in patients with low-level disease activity. The results explored the potential use of MBDA scoring in the increasing numbers of patients who achieved remission, but nonetheless face the risk of RP progression. The 95 patients in the study, who had all been stable on therapy for at least 6 months, were assessed every 3 months up to the 1-year mark. Ma’s group found that MDBA scoring could detect low-grade inflammation in patients who otherwise had little disease activity.⁹

Ronald F. van Vollenhoven, MD, PhD, of the Department of Medicine, Karolinska Institute, presented conclusions from a SWEFOT follow-up study involving patients being evaluated for clinical trials before receiving disease-modifying therapy.⁹ Both MBDA and CRP scores were used to screen patients for participation, but later a group of patients who had qualifying MBDA scores without qualifying CRP scores was included. At intervals of 3 and 12 months, the patients who were initially excluded had similar clinical and RP outcomes. The authors concluded that MBDA scores can be used as a standalone measure, alongside patients screened based on CRP, to select patients for future trials.¹⁰

Plans for Expansion

Myriad’s February announcement of the Crescendo acquisition came 3 years after the company, best known for its genetic tests in cancer, loaned Crescendo $25 million, a deal that also gave Myriad the right to acquire Crescendo in 2014 if certain revenue targets were met.¹ In January 2013, Fierce Medical Devices reported that Crescendo had raised another $28 million in capital, and that some of those funds would be used to expand the sales force and increase penetration beyond the 15% of the rheumatologists in the United States using the test at that time.¹

EBIID

Ronald Rogers, Myriad spokesman, reported in an e-mail to Evidence-Based Immunology and Infectious Disease that as of the end of March 2014, Vectra DA tests were being used by 25% of rheumatologists in the United States. Myriad’s acquisition announcement included plans to expand Crescendo’s presence in Europe² and to use its relationships with commercial insurers to expand coverage for the test, which costs less than $1000. Asked whether it was easier to get coverage for Vectra DA compared with some of Myriad’s more expensive tests in the cancer realm, Rogers replied: “Our managed care team is working with Crescendo to utilize our established managed care relationships to begin expanding private insurance coverage for Vectra DA, and we are optimistic that we can ramp up private payer coverage over the next 12 to 18 months.”