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New Crescendo Data Shows Vectra DA Test Predicts Second-Line Therapy Response in RA Patients


This story has been updated to clarify the role of academic collaborators in presenting data from the studies of Crescendos' Vectra DA.

NEW YORK (GenomeWeb) – Crescendo Bioscience's Vectra DA rheumatoid arthritis test appears to predict response to specific second-line RA drugs, in addition to indicating disease state and potentially predicting disease course, according to new data presented by the firm last week.

Academic collaborators working with Crescendo, a Myriad Genetics subsidiary,  shared the data in a poster at the annual meeting of the American College of Rheumatology in San Francisco last Saturday. They retrospectively compared Vectra DA scores with patient outcomes from a two-arm prospective study of triple therapy versus biologic therapy in patients who failed first-line therapy with methotrexate.

Crescendo initially advanced Vectra DA as a disease monitoring tool, but the company has been working more recently to expand the test's purview to predict RA patients' response to specific therapies, as well as their risk of specific aspects of disease progression, like disease flares.

In 2014, Crescendo presented data hinting that Vectra DA could not only track disease activity and predict aspects of RA progression, but also predict response to specific therapies from a separate analysis of data from the same clinical trial as last week's study.

More specifically, patients whose Vectra DA score decreased the most after three months of methotrexate therapy had a higher likelihood of response to triple therapy than those who did not 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.

In the new analysis, researchers working with the company further crystalized the potential utility of Vectra DA in predicting therapy response even further, from a change in score to a single score measurement correlated with better response to either triple therapy or anti-TNF treatment.

The investigagors, led by Karen Hambardzumyan of Sweden's Karolinska Institute, studied a subset of patients from the Swedish Farmacotherapy (SWEFOT) trial, in which patients were randomized to either Disease-modifying antirheumatic drug (DMARD) therapy or the biologic anti-TNF drug infliximab (Jannsen's Remicade) after failing to respond completely to methotrexate.

Overall, patients in the trial did approximately the same regardless of whether they were treated with infliximab or DMARD triple therapy.

"In terms of the treatment landscape, methotrexate is the gold standard and is where pretty much every patients starts unless it is contraindicated for some reason. And once patients start to not respond to methotrexate, there are then two main strategies. You can add DMARD – disease modifying agents … or there are biological drugs," explained Elena Hitraya, Crescendo's chief medical officer. "But in terms of how to make treatment decision as to one or the other option, though, all of this was an open question," she said.

The researchers hypothesized that Vectra DA score might be able to identify subgroups from SWEFOT with a better response to one or the other of the two therapies, offering for the first time a method of personalizing post-methotrexate drug choices.

To that end, the investigators looked at a set of 157 methotrexate incomplete responders from the trial cohort, comparing their Vectra DA scores prior to starting the next arm of treatment with their response to treatment after one year.

They saw a clear difference in response to the two therapies that was associated with Vectra DA score. Patients with a low score of less than 30 had a significantly greater likelihood of responding to triple therapy than the anti-TNF drug infliximab.

More precisely, 88 percent of low-score patients did well on triple therapy, while only 18 percent responded to infliximab.

Meanwhile, among patients with a high Vectra DA score of greater than 44 prior to therapy, the reverse appeared to be true — only 35 percent responded well to triple therapy, while 58 percent responded to the anti-TNF drug.

Most striking in the results is the implication that a low Vectra DA score could be used to identify a subset of patients who are much more likely to respond to traditional triple therapy than to biologics, which are significantly costlier, Hitraya said.

An open question Crescendo is looking at moving forward is whether Vectra DA could also predict which patients may respond better to one biologic treatment over another, something that could make the test more useful  to clinical practice as the field of available RA drugs expands.

"Anti-TNFs dominate right now," Hitraya said. "For about 90 percent of patients, it's the first-line biologic, and still for 80 percent, it's also the second-line. But with new drugs with different mechanisms of action entering the market, that's something to look at."

Hitraya said that Crescendo has 15 ongoing collaborations with pharmaceutical partners in the RA drug space, ranging from early development to drugs close to coming to market. This raises the potential that Vectra could be advanced someday as a complementary diagnostic, a type of test that is not essential for determining who should receive the drug, but can give doctors an idea of how well their patients might respond to treatment.

In addition to the data on Vectra DA's ability to predict response to anti-TNF or triple therapy presented last week, Crescendo researchers and separate academic collaborators also presented two other studies at the ARA meeting, including one suggesting that Vectra DA could help identify which patients in remission can safely taper off DMARD treatment and which should not.

A third study evaluated Vectra DA score as a predictor of RA disease flare after discontinuation of treatment with anti-TNF therapy. In 439 RA patients who were randomized to stop anti-TNF treatment in the Dutch multi-center POET trial, the researchers found that a high Vectra DA score at baseline was an independent predictor of flare within 12 months of discontinuing therapy.

"Hopefully we are getting to a place with these studies, and more to come, [where we can start to] predict who is going to respond and who can come off of these therapies. These are serious drugs with side effects, and if you are not going to benefit, you don't want to be taking them," said Myriad spokesperson Ron Rogers.

Earlier this year, several physicians expressed skepticism to GenomeWeb that Vectra DA adds enough to the clinical decision-making process to significantly impact patient outcomes despite Crescendo's efforts to collect and disseminate data supporting the test's utility.

In a statement, Myriad said that the company's ACR presentations this year — focusing on the link between Vectra DA score and specific disease events, like flares or recurrences, as well as response to specific therapies — show more directly the potential the test has to help physicians tailor treatment plans for their patients and improve the use of healthcare resources, something that may help persuade clinicians and expand adoption of the assay.

"Personalized medicine is relatively established in oncology, but it's just now becoming [so] in rheumatology," Rogers said.

Crescendo Bioscience president Bernie Tobin told GenomeWeb that currently about 40 percent of rheumatologists use Vectra DA each month.