Researchers presenting data on Crescendo Bioscience's Vectra DA test at the American College of Rheumatology annual meeting late last month shared a number of studies supporting the potential of the test not just for disease monitoring, but also to predict patients' risk of joint damage.
Crescendo's Vectra DA is a blood-based test that measures the levels of 12 proteins associated with rheumatoid arthritis, yielding a test score between one and 100 that is intended to help doctors determine whether a patient has high, moderate, or low RA disease activity.
The company announced this July that Medicare contractor Palmetto GBA had agreed to reimburse for the test, which the company performs through its CAP-accredited, CLIA-certified lab (PGx Reporter 7/10/2013)
Previous scientific presentations by Crescendo have largely focused on the test as a disease monitoring tool. But at the ACR meeting this year several studies — among a group of three oral presentations and a handful of posters — also tracked the test's ability to predict patients' risk of developing joint damage, based on the Vectra DA score's correlation with radiographic measurements of changes in patients' joints.
According to Oscar Segurado, Crescendo's chief medical officer, the company is working to build up scientific evidence to support the test's use not only for disease monitoring and predicting joint damage but also to track response to RA therapies, and to indicate whether a patient is in clinical remission, which could potentially help physicians make decisions about when to taper or discontinue treatment.
"The framework of our presentations at ACR reflects scientific and clinical data we have been generating to demonstrate clinical utility and value of the test in three areas of RA disease management: clinical uncertainty, prediction of joint damage, and monitoring of the disease," Segurado told PGx Reporter this week.
The new data on joint damage risk doesn't represent a research shift for the company, but rather a tipping point in terms of having been able to collect data from studies that clearly demonstrate this aspect of the tests clinical utility, he said.
In one oral presentation at the meeting, researchers focused on data from a study by the Leiden Early Arthritis Clinic in The Netherlands. The group reported a correlation between Vectra DA score and risk of radiographic progression over a 12-month period — independent of CRP levels — in 163 disease-modifying anti-rheumatic drug-treated patients.
According to the team's poster, "radiographic progression increased non-linearly with increasing [test] scores, with the greatest increase in risk observed for scores in the 40−60 range, and the greatest risk observed for MBDA scores [at or above] 60."
The results also indicated that Vectra DA's association with joint damage risk is independent of other clinical risk variables. According to the researchers, in subgroups of patients with low DAS28-CRP or low CRP concentrations, there was still a clear relationship between increasing Vectra DA score and increasing risk of radiographic progression. Also, among seropositive patients — who as a group are expected to be at increased risk for joint damage, according to the researchers — patients with lower scores were less likely to have radiographic progression.
In a poster by the same group, also presented at the conference, the Leiden team showed that Vectra DA measured at baseline predicted the degree of radiographic progression observed after one year, and that Vectra DA score at that one-year mark was in turn able to predict progression over the second year.
According to the team, the results suggest the test could help rheumatologists identify patients at high risk for radiographic progression and potentially change their treatment strategy in order to prevent resulting joint damage.
In another oral presentation, Crescendo representatives and collaborating researchers from the Karolinska Institute in Sweden presented data from the SWEFOT study, a Swedish study evaluating patients with early RA who were started on methotrexate therapy and re-assessed at three months and after a year.
The group assessed the ability of Vectra DA, as well as its 12 individual biomarkers, measured at baseline, to predict clinical response to therapy at three months and radiographic progression after one year. The team found that the Vectra DA score significantly improved after three months in the patients who had responded to methotrexate treatment. In addition, Vectra DA score at baseline was independently associated with radiographic progression at the one-year mark.
This data was also detailed in a poster at the meeting, where the Karolinska group reported that high Vectra DA score at baseline was associated with a higher risk of radiographic progression in their cohort, even in patients who had moderate disease activity assessed by DAS28 or low CRP at baseline. In addition, 98 percent of patients who had rapid radiographic progression at one year had a high Vectra DA score at baseline, independent of CRP level, the group reported.
In another poster presented at the meeting, Crescendo Bioscience and researchers from the University of Occupational and Environmental Health in Kitakyushu, Japan, shared data from a study of patients treated with TNF inhibitors adalimumab, etanercept, or infliximab.
The group found that patients who had a low Vectra DA score (29 or less) in at least two of three study visits over one year were much less likely — with an odds ratio of 14.3 — to show progression toward joint damage compared to patients who had low scores for only one visit. Meanwhile, patients with high Vectra DA scores (greater than 44) for at least two of three visits had a much higher risk — an odds ration of 15.3 — of clinically relevant radiographic progression versus those with a high score at only one visit.
A fourth poster presentation by Danish researchers and Crescendo looked at the association of baseline Vectra DA score and changes in the score after six weeks, with MRI-indicated joint inflammation, rather than radiographic progression.
"This data really shows for the first time that a blood test is able to correlate with future joint damage, as measured by radiographic progression over time. And we were able to show we were significantly better than DAS28 and CRP in the SWEFOT study," Segurado said.
"If you look at the study, we conducted a very precise analysis using cumulative probability plots … and we were able to show in a very distinct way how the lines representing patients with a high, moderate, and low score are distinguished from each other [in terms of joint damage risk] so when you have a high score — over 44 — you are going to have a higher likelihood of radiographic progression which is going to lead to disabilities. It is clearly differentiated from either DAS28 or CRP, where those three lines overlap," he said.
In addition to the data focused on the test's association with risk of future joint damage, the presentations at the ACR meeting also included another study looking at the test's strength in tracking disease activity even in the presence of comorbid conditions like fibromyalgia.
In this presentation, researchers from Brigham and Women’s Hospital and Harvard Medical School found that the presence of fibromyalgia markedly increased disease activity measures based on clinical assessments like tender joint count, DAS28-CRP, and Patient Global Assessment. In contrast, the Vectra DA test measured essentially the same level of disease activity in patients with RA independent of the presence of fibromyalgia or low CRP, the group reported.
According to Segurado, demonstrating this kind of objectivity and independence for Vectra DA is also an important scientific goal for the company right now.
He also said that Crescendo has several studies in the works on Vectra DA's ability to be a more precise indicator of RA remission. "This may have tremendous health economics implications in helping physicians decide when to taper off or withdraw therapy," he said.
And, Segurado said, the company is also planning a prospective study of how Vectra DA influences physician decision-making.
Crescendo earlier this year secured $28 million through a Series D financing round, which it has been using to expand its sales force, educate rheumatologists about Vectra DA, and drive adoption and coverage of the test (PGx Reporter 1/9/2013). Medicare coverage represents a key milestone for Crescendo in increasing use of its flagship test.
According to the company, Crescendo has reached a milestone of 100,000 total tests performed.
Segurado said that the company's next test development target will be diseases that are close to rheumatoid arthritis, like its childhood-onset form, juvenile idiopathic arthritis. "We also have plans for psoriatic arthritis and ankylosing spondylitis," he said.
Within rheumatoid arthritis itself, the company also thinks there may be other applications for Vectra DA, or a "tweaked" version of the algorithm, such as predicting which patients are at higher risk of cardiovascular disease.
According to Segurado, Crescendo also recently concluded a prospective study looking at the possibility that Vectra DA could help predict response to anti-TNF therapy.