Literature Review

Serum neurofilament light chain level may indicate MS disease activity


 

FROM JAMA NEUROLOGY

In patients with multiple sclerosis (MS), serum neurofilament light chain (sNfL) levels are associated with brain atrophy, according to an investigation published online August 12 in JAMA Neurology. Furthermore, changes in sNfL levels are associated with disability worsening, and sNfL levels may be influenced by treatment. These data support the potential of sNfL as an objective surrogate of ongoing MS disease activity, according to the researchers.

Neuronal and axonal loss increase levels of NfL in cerebrospinal fluid (CSF) in patients with MS. Previous research indicated that sNfL levels are correlated with CSF levels of NfL and are associated with clinical and imaging measures of disease activity. For the purpose of repeated sampling, collecting blood from patients would be more practical than performing lumbar punctures, said the investigators. No long-term studies of sNfL concentrations and their associations with MS disease outcomes had been performed, however.

Ester Cantó, PhD, of the University of California, San Francisco (UCSF), and colleagues examined data from the prospective Expression, Proteomics, Imaging, Clinical (EPIC) study to assess sNfL as a biomarker of MS disease activity and progression. The ongoing EPIC study is being conducted at UCSF. Dr. Cantó and colleagues analyzed data collected from July 1, 2004, through August 31, 2017, for 607 patients with MS. Participants underwent clinical examinations and serum sample collections annually for 5 years, then at various time points for as long as 12 years. The median follow-up duration was 10 years. The researchers measured sNfL levels with a sensitive single-molecule array platform and compared them with clinical and MRI variables using univariable and multivariable analyses. Dr. Cantó and colleagues chose disability progression, defined as clinically significant worsening on the Expanded Disability Status Scale (EDSS) score, and brain fraction atrophy as their primary outcomes.

The population’s mean age was 42.5 years. About 70% of participants were women, and all were of non-Hispanic European descent. At baseline, sNfL levels were significantly associated with EDSS score, MS subtype, and treatment status.

Dr. Cantó and colleagues found a significant interaction between EDSS worsening and change in levels of sNfL over time. Baseline sNfL levels were associated with approximately 11.6% of the variance in participants’ brain fraction atrophy at year 10. When the investigators controlled for sex, age, and disease duration, they found that baseline sNfL levels were associated with 18% of the variance in brain fraction atrophy at year 10. After 5 years’ follow-up, active treatment was associated with lower levels of sNfL. High-efficacy treatments were associated with greater decreases in sNfL levels, compared with platform therapies.

More frequent sample acquisition could provide greater detail about changes in sNfL levels, wrote Dr. Cantó and colleagues. They acknowledged that their study had insufficient power for the researchers to assess the outcomes of individual MS therapies. Other limitations included the lack of data on NfL stability and the lack of a group of healthy controls.

“For an individual patient, the biomarker prognostic power of sNfL level for clinical and MRI outcomes was limited,” said the investigators. “Further prospective studies are necessary to assess the assay’s utility for decision making in individual patients.”

The National Institutes of Health and the U.S. National MS Society supported the study. Several of the investigators received compensation from Novartis, which provided funds for the reagents needed for the single-molecule array assay.

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