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Molecular Testing Could Allow for Greater Precision in Treating RA

Kelly Davio
While the emergence of new antirheumatic agents—including biologics—has revolutionized the treatment of rheumatoid arthritis (RA), these drugs come a high cost to the healthcare system. Furthermore, many patients who receive these drugs may not respond to therapy, thereby increasing costs without improving outcomes.
While the emergence of new antirheumatic agents—including biologics—has revolutionized the treatment of rheumatoid arthritis (RA), these drugs come a high cost to the healthcare system. Furthermore, many patients who receive these drugs may not respond to therapy, thereby increasing costs without improving outcomes, and many patients may not respond to therapy, but existing tools, such as C-reactive protein (CRP), are not predictive enough to make delivery of the right treatment to the right patient at the right time consistently achievable.

During the American College of Rheumatology Annual meeting, held October 19-24 in Chicago, Illinois, 2 research teams examined the potential for a multibiomarker disease activity score to better predict response to antirheumatics, including tofacitinib (Xeljanz) and rituximab (Rituxan). 

The first team, from the David Geffen School of Medicine at the University of California Los Angeles, used the test (sold under the brand name Vectra DA) to measure 12 inflammatory biomarkers together with a baseline power doppler assessment to assess whether their measurements could predict response to tofacitinib in patients with RA.The researchers found that, in the 25 enrolled patients, the doppler score and the Vectra score were predictive of the clinical disease activity index scores and disease activity scores in a count of 28 joints (DAS28) at 12 weeks of treatment. 

Similarly, a team from University Medical Center Utrecht reviewed 3 cohort studies representing 57 patients with RA who were treated with rituximab and methylpresnisone and found there was a significant correlation between the multibiomarker score and DAS28 with erythrocyte sedimentation rate and CRP at baseline and at 6 months.2

Elena Hitraya, MD, PhD, chief medical officer of Crescendo Bioscience, which developed the test, told The American Journal of Managed Care® in an interview that the company is also in the process of submitting a paper that demonstrated that the test was approximately 3 times more predictive of joint progression than existing disease activity measures, and that the test was also a better predictor of progression when adjusted for patients’ age and adiposity. 

Hitraya said that using the test could help patients be prescribed appropriate therapies faster, and bringing RA into low disease activity quickly has significant implications for cost savings. It could also spare patients and health systems the burden of having to cycle through multiple ineffective treatments. 

However, an equally important benefit could be preventing radiographic progression in patients who appear to be responding well to treatment. Hitraya explained that, in some cases, patients may feel that their disease is improving with treatment, but they may still have a high multibiomarker test score 6 months after initiating a therapy. As the score is linked with the risk of radiographic progression, patients can be tested at 6 months to identify whether they are still at risk of disease progression despite improvement in symptoms so that their regimen can be amended. On the other hand, in treating patients who still have pain despite treatment, a low test score (and thus a low risk of radiographic progression) at 6 months can allow the clinician to investigate and address common comorbidities that may be contributing to patients’ symptoms. 

Despite the potential benefits of molecular testing—and despite the fact that Medicare and Medicaid reimburse for Vectra and rheumatology provider groups, such as United Rheumatology and Bendcare, have endorsed the use of Vectra as a way to improve patient care—commercial plans have been slow to adopt the test.

However, according to Hitraya, that could be changing. When her company talks with commercial payers about what matters to them most, she said, “the strongest evidence is in the radiographic changes and progression as an objective measure.” Thus, her team is working with multiple payers on collaborative studies that can help them to gain confidence in the test. 

Gathering more data to support use of the test has begun to pay rewards; Kroger Prescription Plans announced in July of this year that it will offer the test as a benefit option for employer group clients, calling it a “highly attractive diagnostic test for our members” for its ability to optimize pharmaceutical spending for patients with RA.

References

1. Razmjou A, Brook J, Kaeley G, Elashoff D, Ranganath VK. Baseline power doppler and MBDA score predicts 12-week disease activity response to tofacitinib. Presented at the American College of Rheumatology 2018 meeting, October 19-24, 2018; Chicago, Illinois. Abstract 582. https://acrabstracts.org/abstract/baseline-power-doppler-and-multi-biomarker-disease-activity-score-predict-12-week-disease-activity-response-to-tofacitinib/.

2. Roodenrijs NMT, de Hair MJH, Wheater G, et al. The multi-biomarker disease activity score tracks response to rituximab treatment in rheumatoid arthritis patients: a post-hoc analysis of 3 cohort studies. Presented at the American College of Rheumatology 2018 meeting, October 19-24, 2018; Chicago, Illinois. Abstract 1500. https://acrabstracts.org/abstract/the-multi-biomarker-disease-activity-score-tracks-response-to-rituximab-treatment-in-rheumatoid-arthritis-patients/.

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