Serum Neurofilament Light Chain in Determining Multiple Sclerosis Disease Activity

Serum neurofilament light chain (sNfL) percentiles in addition to Z scores can help identify patients with multiple sclerosis (MS) who are at risk for detrimental disease courses, according to recent findings published in the Lancet Neurology.

“The absence of representative reference values to correct for physiological age-dependent increases in sNfL has limited the diagnostic use of this biomarker at an individual level. We aimed to assess the applicability of sNfL for identification of people at risk for future disease activity by establishing a reference database to derive reference values corrected for age and body-mass index (BMI),” wrote Pascal Benkert, PhD, Department of Clinical Research, Clinical Trial Unit, University Hospital Basel, University of Basel, Basel, Switzerland, and co-researchers.

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Using a reference database, Benkert et al examined sNfL as an endpoint of effectiveness across disease-modifying therapies. A control group of participants with no central nervous system (CNS) disease from four cohort studies in North America and Europe was also created.

“We modelled the distribution of sNfL concentrations in function of physiological age-related increase and BMI-dependent modulation, to derive percentile and Z score values from this reference database, via a generalized additive model for location, scale, and shape,” explained Dr Benkert et al.

The Swiss Multiple Sclerosis Cohort was used to test the reference database for participants with MS. Researchers compared clinical and MRI characteristics with association of sNfL Z scores.

A total of 10,133 blood samples from 5390 people were recorded in the control group, which showed group saw a rise in SNfL concentrations with age. Additionally, 7769 samples from 1313 participants with MS were collected from the Swiss Multiple Sclerosis Cohort, which showed sNfL percentiles and Z scores increasing risk for future acute and chronic disease activity.

In participants with MS, an sNfL Z score that was more than 1.5 has an association with risk of future clinical and MRI disease activity. Similar outcomes were recorded in stable participants with no disease activity.

“At the group level, the longitudinal course of sNfL Z score values in people with multiple sclerosis from the [Swiss Multiple Sclerosis Cohort-Study] decreased to those seen in the control group with use of monoclonal antibodies and, to a lesser extent, oral. However, longitudinal sNfL Z scores remained elevated with platform. Results were fully supported in the validation cohort (n=4341) from the Swedish Multiple Sclerosis registry,” Dr Benkert et al concluded.

Researchers interpreted that the use of sNfL percentiles and Z scores can help identify patients with MS who are at risk for detrimental disease courses.

Reference

Benkert P, Meier S, Schaedelin S, et al. Serum neurofilament light chain for individual prognostication of disease activity in people with multiple sclerosis: a retrospective modelling and validation study. Lancet Neurol. 2022;21(3):246-257. doi:10.1016/S1474-4422(22)00009-6