Octave’s blood test accurately captures MS disease activity: Study

A test that assesses the levels of 18 proteins in the blood and uses artificial intelligence algorithms can help to measure the level of new disease activity in multiple sclerosis (MS), according to a new study.

The test, developed by Octave Bioscience, is already available to MS patients in the U.S. and is currently used in routine clinical practice across multiple leading institutions and pharmaceutical studies.

The test’s validation was described in “Clinical validation of a multi-protein, serum-based assay for disease activity assessments in multiple sclerosis,” which was published in Clinical Immunology. The work was funded by Octave and the U.S. Department of Defense.

“The data published in this study represent a major advancement in providing deeper insights for the MS community,” Ferhan Qureshi, vice president of biomarker product development at Octave, said in a company press release.

“The clinical validation of this test is a meaningful step forward for the providers and researchers working to glean a more complete understanding of a patient’s MS and how the disease can vary between individuals,” said Tanuja Chitnis, MD, director of the Mass General Brigham Pediatric MS Center and co-author of the study.

MS is caused by inflammation in the brain and spinal cord, which damages the myelin sheath, a fatty covering around nerve fibers. Damage to myelin interferes with nerve signaling, causing MS symptoms.

MS is a very heterogeneous disease, meaning its activity and progression can vary widely among people. While MRI scans can help track disease activity to some extent, these are expensive and are usually performed only every six months to two years, so there’s still a need for better ways to routinely measure MS activity.

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How does Octave’s MSDA test work?

Octave’s MS disease activity (MSDA) test measures levels of 18 proteins in the blood. The proteins were selected based on analyses of more than 1,000 candidate proteins in blood samples from thousands of patients.

Based on the proteins’ levels, algorithms calculate an overall disease activity score, along with subscores related to four different disease processes — immune activity, inflammation in the nervous system, myelin biology, and nerve fiber damage.

“The test interrogates multiple biological pathways important in MS pathophysiology with a diverse set of biomarkers to provide a highly sensitive, dynamic perspective of disease at the subclinical level. This provides an important complement to clinical evaluation of signs and symptoms of disease and MRI findings,” Qureshi said.

In this study, scientists evaluated how well the test could identify patients at risk of new disease activity. The analysis included data from 614 people with MS. Of these samples, 426 were used to train the algorithms that interpreted the MSDA test. The remaining 188 samples were used to evaluate its accuracy.

The researchers looked at three measures of disease activity — actively inflamed lesions, new or enlarging lesions, and overall disease activity (as measured by MRI scans and/or clinical signs).

To assess the test’s accuracy, the scientists used a statistical measure called the area under the receiver operating characteristic curve (AUROC), a benchmark of how well a test can differentiate between two groups — in this case, patients with or without disease activity. AUROC values range from 0.5 to 1, with higher numbers indicating better performance.

The MSDA test had an AUROC of 0.781 for identifying inflamed lesions, 0.75 for new or enlarging lesions, and 0.768 for overall disease activity. The accuracy of the 18-protein test was notably higher than any test using only one blood protein marker, including the neurofilament light chain (NfL), a marker of nerve damage used to assess disease activity in neurodegenerative conditions.

“Our analysis revealed that the multi-protein model outperformed single-protein models … which indicated a more accurate representation of the various pathways, processes, and cell types involved in a complex disease state, such as MS, by a combination of biomarkers,” the researchers wrote.

What the MSDA scores mean

People with moderate to high MSDA scores were more than four times as likely to have at least one inflamed lesion, compared to those with low scores, statistical tests showed. Patients with a high MSDA score were more than 20 times as likely to have two or more such lesions.

People treated with high-efficacy MS therapies, such as anti-CD20 antibodies or Tysabri (natalizumab), tended to have lower MSDA scores than those on lower-efficacy therapies.

“We are encouraged that these results validate the performance of the Octave MSDA Test and demonstrate its ability to quantitatively and objectively measure disease activity of patients with MS,” Qureshi said.

The study “supports a validated multivariate blood test that correlates with new MRI lesions in MS patients and can allow for improved monitoring of disease activity,” Chitnis said.

The researchers said the test could monitor disease activity and track responses to treatment in routine MS clinical practice, but noted further validation is needed, particularly in more diverse populations, as most patients in this analysis were white. Cost-effectiveness assessments should also be done to ensure the test is offered at a cost that reflects its value in the context of MS care, which is expensive, they said.