What’s Holding Back Biomarker Innovation, & How Can We Solve It?

Think about it. Most rheumatology labs are stuck in the 1960s. Translational biomarker research looks excellent on paper and in theory. However, many barriers exist from the bench to the bedside. This article highlights this problem for the rheumatology community and proposes practical solutions.

Case in Point

For an example, let’s examine systemic lupus erythematosus (SLE). SLE is the 14th most common cause of death, excluding accidents and suicide, in all U.S. women aged 15–64 years old, and the fifth or sixth cause for women of color aged 15–34.¹ The average time to SLE diagnosis from symptom onset is four to six years; patients with longer delays have more severe disease and permanent organ damage.^2-4

This is no surprise. Our SLE biomarkers, henceforth called ancient biomarkers (e.g., anti-dsDNA, C3, C4, anti-Smith, anti-RNP, anti-SSA), are more than 50 years old.

Using ancient biomarkers, rheumatologists misdiagnose many SLE patients as healthy or having other disorders, only to have their SLE properly diagnosed later when they have more severe disease.⁵ We also misdiagnose non-SLE patients as having SLE, treating these patients inappropriately with high-dose glucocorticoids.⁶ The ancient biomarkers also lead to difficulty assessing disease activity, which is crucial in guiding proper management.⁷

During the past two decades, improved SLE biomarkers have become available. However, most insurance companies refuse to pay for them. This negatively impacts patients and clinicians while dissuading lab research companies and investors from pursuing biomarker research and development (R&D). Biomarkers that ultimately survive end up in the hands of the giant insurance-backed laboratories LabCorp and Quest (i.e., the duopoly), which typically do not invest in their R&D.

Medical System Failures

Consider the proprietary biomarker, the SLE-key rule-out test (by ImmunArray). This test would identify numerous autoantibody and immune system molecular patterns and indicate if a patient does not have SLE. A positive result could rule out SLE with a 94% sensitivity, 75% specificity and a 93% negative predictive value.⁸ Despite these impressive performance characteristics, ImmunArray couldn’t navigate the complicated and expensive lab approval system and the absence of insurance support that forced patients to pay for the test out of pocket. ImmunArray ultimately filed for bankruptcy, and the SLE-key test is no longer commercially available.

At other times, research biomarkers have been offered cheaply by the commercial lab duopoly of LabCorp and Quest to the financial detriment of the companies that developed such tests in the first place. Diffuse fine speckled-70 antinuclear antibody (DFS-70) helps to discriminate between the likelihood of systemic autoimmune disease in ANA-positive patients who are negative for disease-specific autoantibodies.⁹ The test was developed by a proprietary lab (Inova), which develops tests for research rather than clinical purposes. The test can now be ordered through LabCorp.