NEW YORK (GenomeWeb) — Data presented earlier this month at the 2014 European League Against Rheumatism (EULAR) Annual Congress by Crescendo Bioscience has added upon earlier retrospective data supporting the clinical utility of the company's Vectra DA test in measuring disease activity and predicting joint damage in rheumatoid arthritis patients.
Presentations also provided the first evidence that the multi-protein biomarker test may also be able to predict response to different second-line therapies in patients who appear, clinically, to be unresponsive to methotrexate.
Crescendo's Vectra DA is a blood-based test that measures the levels of 12 RA-associated proteins. The test classifies patients using a score between one and 100 intended to help doctors determine whether a patient has high, moderate, or low RA disease activity.
The company has mainly focused on marketing the test as a disease monitoring tool, but has begun recently to build evidence on the test's ability to predict RA patients' risk of joint damage and their response to different therapies.
Earlier this year, Crescendo published results in Annals of the Rheumatic Diseases of a retrospective analysis of data from the Swedish Farmacotherapy (SWEFOT) clinical trial that demonstrated that Vectra DA scores taken when patients began treatment were predictive of later joint damage over the following year as measured by radiographic imaging.
One poster presented at EULAR this month by Karen Hambardzumyan of Sweden's Karolinska Institute built this study out further, showing that Vectra DA scores measured in patients at three months and 12 months remained predictive of radiographic joint damage progression over up to two years of follow up.
According to the study authors, patients with a high score at baseline but subsequent lowering of MBDA score in response to treatment had a lower risk of joint damage, whereas patients with a persistently high score had up to 42% risk of radiographic progression.
Rebecca Bolce, senior director, medical affairs at Crescendo, and an author of the company's main SWEFOT study, told ProteoMonitor this week that she was excited to see this data demonstrate that Vectra DA not only identifies patients at baseline as being at high or low risk for subsequent damage, but that changes in patient scores during treatment are also predictive of later damage.
"By assessing at multiple time points after initiating different therapies you can continue to identify patients at higher or lower risk. This was very important from a clinical utility standpoint," Bolce said.
Data from SWEFOT also informed a separate poster presentation by Hambardzumyan, which suggested that Vectra DA may also have utility in predicting response to different therapies in patients who do not initially respond to methotrexate.
In this analysis, researchers looked at a subset of SWEFOT patients who did not respond to three months of initial methotrexate therapy and who were then randomized to receive either non-biological DMARD triple therapy or anti-TNF (infliximab) therapy.
The group found that in patients who had inadequate clinical responses to three months of methotrexate, some showed changes in their Vectra DA score, while others did not. Those whose Vectra DA score lowered the most after three months had a higher likelihood of response to triple (DMARD) therapy — based on achieving low DAS28 or good EULAR response criteria — than those who didn't show molecular changes after three months of methotrexate.
Patients with smaller decreases in their Vectra DA score, meanwhile, were more likely to respond to anti-TNF therapy.
"This was our first data set trying to associate with response to a particular therapy," Bolce said. Though early and retrospective, the data suggest that Vectra DA could help physicians choose how to treat patients that fail to respond to methotrexate. Additional validation will be necessary to confirm this is true.
Another question not answered by the company's studies so far, is whether using Vectra DA to monitor disease, predict joint damage, or guide treatment decisions actually improves patient outcomes.
Bolce said the company is thinking about the best way to potentially perform an appropriate outcomes study.
Crescendo and SWEFOT researchers also presented a separate data analysis at the meeting that suggested that Vectra DA might offer a way for pharmaceutical companies and researchers to recruit more patients into RA drug trials without harming their chances of success with a particular therapy.
In this analysis, researchers led by the Karolinska Institute's Ronald van Vollenhoven concluded that using Vectra DA scores of over 44 as a cutoff point, rather than the current standard of a CRP level over 10 mg/L, could bring more patients into RA clinical trials.
In the SWEFOT cohort, the authors wrote, such a strategy could have raised the number of DMARD-naïve patients by 24 percent and the number of eligible MTX Non-responder patients by 47 percent "with a comparable response to treatment and subsequent radiographic progression."
Additional studies on Vectra DA presented at the conference by a variety of other researchers working with Crescendo included data showing that Vectra DA score correlated with the amount of joint inflammation detected by ultrasound imaging, as well as high-resolution CT scans of joints, even in patients with low clinical disease activity or those in remission.
Other data by Seattle Children’s Hospital and Research Institute researchers working with Crescendo found a significant association between Vectra DA score and clinical disease activity in 90 patients with idiopathic juvenile arthritis from the Trial of Early Aggressive Therapy in JIA cohort.
Crescendo collaborators from the University of Occupational and Environmental Health in Japan also reported on using Vectra DA to evaluate treatment response in a clinical trial of the biologic agent tofacitinib. In this study, researchers found that leptin, one component of the Vectra DA biomarker panel, increased with active treatment.