A Closer Look at Biomarker-Based Disease Activity Measures in RA

Rheumatology Advisor spoke with Jeffery R Curtis MD, MS, MPH, Harbert-Ball Endowed Professor of Medicine, University of Alabama at Birmingham, about 2 studies presented at the 2019 American College of Rheumatology/Association of Rheumatology Professionals (ACR/ARP) Annual Meeting, held in Atlanta, Georgia. Both studies evaluated the potential of the multibiomarker disease activity (MBDA) blood test, Vectra^®, in measuring disease activity among patients with rheumatoid arthritis (RA).

In the first study, researchers combined data from separate cohorts to validate the MBDA score as a predictor of radiographic progression and as a continuous variable to predict risk for radiographic progression in RA. Results indicated that radiographic progression risk was nearly absent with low MBDA scores and was >40% with the highest MBDA scores.¹ The second study was conducted to validate cardiovascular (CV) risk prediction score in RA, and results demonstrated a good accuracy of the biomarker-based test.²

Recently, the MBDA score/Vectra test was also added to the updated 2019 ACR recommendations for RA disease activity measures for regular use.

Rheumatology Advisor: Dr Curtis, could you tell us the highlights of the 2 studies based on the biomarker-based test in RA presented at ACR 2019?

Jeffery Curtis, MD: The studies that we’re talking about are based on Myriad Genetics’ Vectra, a simple blood test that measures disease activity in RA. This test is commercially available and has been around in [clinics across the country], including my own, for quite a number of years.

The new research presented at this meeting explored the Vectra test and the inflammation that is being measured by it, to help predict the future risk for irreversible joint damage. The relevance of this research is that we currently do not have tools [to measure inflammation in RA]. We may be able to assess patient [data] based on how they are doing and feeling, but we do not have tools to help understand what the risk for certain conditions, including irreversible joint damage, might be in the future. Therefore, the idea is to give [patients with RA] a prediction or risk score for radiographic progression.

The second, and somewhat thematically related, abstract [presented at ACR 2019], was also based on the Vectra test. With other easily collectable risk factors, this test would help predict patients’ future risk for CV events. The relevance here is that [comorbidities such as these] are what kills patients with RA; these patients have about a 50% increased risk for a CV event.³ Therefore, apart from identifying patients at high risk on the basis of traditional risk factors, the Vectra test assesses level of inflammation in patients with RA.

Rheumatology Advisor: The Vectra test has been reported to be a better quantitative measure of disease activity than conventional methods. Can you discuss this further?

Dr Curtis: The test was trained against traditional measures of disease activity assessment, including the disease activity score in 28 joints. This model was formative in the development of the [Vectra test]. It has also been recognized that joint examinations by physicians aren’t perfect, and there may be patients who are hard to assess. Compared with standard clinical practices that involve disease activity assessment, the Vectra test also helps inform the future. For example, there may be patients with severe damage and [uncontrolled levels of inflammation] where we may have to consider changing medicines or treatments, and the Vectra test helps do that.

Rheumatology Advisor: Would the Vectra test be helpful in early diagnosis and screening for RA?

Dr Curtis: Early diagnosis and screening might be a bit beyond the testing, as it is only validated for use in patients already diagnosed with RA. Where [Vectra’s] real strength lies is in assessing patients who are, for example, on an every 6 months schedule. Instead of returning to their doctor’s office only every 6 months, patients can take the Vectra test at other times and locations as well. This system may provide important insights; for example, a patient has been doing great at every 6-month visit, but suddenly their Vectra score has increased and perhaps their patient-reported outcomes have changed, too. We, as clinicians, should not be waiting for 6 months and must get the patient back in to reevaluate. Vectra has provided that critical clue to inform and make such an important change.

Rheumatology Advisor: What is the future direction of these studies presented at ACR 2019? Do you have any final thoughts on the subject?

Dr Curtis: Gaining additional specificity and validation is where I want to see Vectra go. As with any prediction test, there will be constant evolution, which will happen like with the other diagnostic or predictive tests. An interesting near-term objective would be, how do we use Vectra in an effective manner to communicate with patients that, in turn, helps motivate them to want to do better and to strive for remission? Many doctors see the Vectra test as a more objective measure of disease activity, and these studies [presented at ACR 2019] are an extension of it, of predicting future radiographic progression or CV events. I think it’s pretty exciting to think about how doctors can effectively use the test because, in some sense, it’s a teaching tool, it’s a window of opportunity to have a discussion.

My hope and goal are that we continually find ways to strive to motivate patients to want to do better, specifically those who are passive and wait for their doctors to recommend treatment changes. [We could explain concepts like the Vectra test] in a way that patients understand and they could be responsible for wanting to do better rather than passively waiting for their doctors. Just like how patients now understand unacceptable levels of blood pressure, we want them to have a similar comfort with unacceptable levels of RA disease inflammation and what it may lead to in the future. It is an exciting opportunity to facilitate shared decision making, where patients understand that they want to do better and strive for remission. Currently, the concept of remission, be it biomarker based or any of the other ways, is not centered on treatment between patients and doctors making decisions.

Disclosure: Dr Curtis declared an affiliation with Myriad Genetics.

References

1. Huizinga T, Weinblatt M, Shadick N, et al. Predicting risk of radiographic progression for patients with rheumatoid arthritis. Presented at: 2019 ACR/ARP Annual Meeting; November 8-13, 2019; Atlanta, GA. Abstract 466.

2. Curtis J, Xie F, Crowson C, et al. Derivation and validation of a biomarker-based cardiovascular risk prediction score in rheumatoid arthritis. Presented at: 2019 ACR/ARP Annual Meeting; November 8-13, 2019; Atlanta, GA. Abstract 2350.

3. Chodara AM, Wattiaux A, Bartels CM. Managing cardiovascular disease risk in rheumatoid arthritis: clinical updates and three strategic approaches. Curr Rheumatol Rep. 2017;19(4):16.