Early Serum NfL Tied to Long-Term MS Brain Changes

DALLAS -- Early levels of serum neurofilament light chain protein (NfL) may help identify multiple sclerosis (MS) patients at risk for more severe disease who may need aggressive treatment, researchers reported here.

Serum NfL values in the first few years after MS onset were tied to long-term measures of brain lesion load and atrophy, according to a longitudinal analysis presented by Tanuja Chitnis, MD, of Brigham and Women's Hospital in Boston, and colleagues, at the 2019 Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) forum.

"There's evolving work showing that serum NfL correlates with the presence of new MRI lesions, with the presence of new attacks, and in general with treatment response," Chitnis told MedPage Today. "On that background -- which mostly includes short-term studies evaluating NfL over 2 or 3 years, sometimes up to 5 years -- we asked whether serum NfL levels had any impact on long-term outcomes."

In many neurodegenerative diseases, NfL has potential as a biomarker because it directly reflects neuronal degeneration, observed Tobias Derfuss, MD, of University Clinic in Basel, Switzerland, who was not part of the study.

"MRI captures neurodegeneration only in a time frame of years because brain atrophy develops very slowly and atrophy measurement in MRI is prone to artifacts like dehydration," Derfuss told MedPage Today. "In contrast, NfL gives a snapshot of currently ongoing neurodegeneration."

"This feature has obviously the caveat of how much a single NfL measurement might tell about the future," he added. "Multiple longitudinal measurements outside periods of inflammation might reflect better the background neurodegeneration that might be correlated with long-term disability development."

In this study, Chitnis and colleagues identified 122 patients from the CLIMB (Comprehensive Longitudinal Investigations in MS at Brigham and Women's Hospital) database who had annual blood samples for up to 10 years. They measured serum NfL using a highly sensitive single molecule array assay and averaged NfL values across multiple time points.

The researchers looked for correlations with several 10-year outcomes including T2 hyperintense lesion volume (T2LV) and brain parenchymal fraction (BPF), a surrogate of whole brain atrophy, from high-resolution 3T MRI and Expanded Disability Status Scale (EDSS) scores.

Averaged annual NfL values were negatively associated with BPF and T2LV, but "the significance was in the first 3 years of NfL values; they really had the highest impact on longer-term MRI outcomes," Chitnis said.

Approximately 15% to 20% of the BPF variance and T2LV could be predicted from early averaged annual NfL levels. "There was very little additional information gained after those first few years," she noted.

"As a clinician, this tells me that the early years are the most critical period to get the disease under control and treat patients with the most appropriate therapies," she added. "That was quite eye-opening."

A limitation of the study was that it did not find a significant correlation between NfL and 10-year EDSS scores or other long-term measures of disability. "However, this is likely because the CLIMB cohort is a highly managed, highly treated group of patients," Chitnis explained.

The authors declared no conflicts of interest.

Source: https://www.medpagetoday.com/meetingcoverage/actrims/78324

Monitoring disease activity in multiple sclerosis using serum

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