Applicability of sNfL measurement in clinical practice

Elevated baseline serum neurofilament light (sNfL) levels were associated with longitudinal brain atrophy and the development of new T2 lesions in patients with MS. The results were consistent across demographical and clinical subgroups [1]. First small steps were proposed towards the routine use of sNfL measurements in clinical practice [2].

NfL is a neuronal protein that reflects axonal damage in the cerebrospinal fluid of patients with MS [3]. Serum NfL levels can be used as a marker of drug response and can predict future disease activity in patients with MS [4]. According to Prof. Elias Sotirchos (Johns Hopkins University, MD, USA) there is evidence that sNfL is linked to clinic-radiological measures of inflammatory disease activity. However, assessments of sNfL in large heterogenous MS populations are scarce. The study evaluated the relation between sNfL levels, longitudinal brain atrophy, and new T2 lesion development in patients from the real-world, multicentre, prospective MS Partners Advancing Technology and Health Solutions (MS PATHS) network cohort. Biospecimens were collected from 6,968 participants from the MS PATHS cohort and 201 healthy controls. The assessment of sNfL levels was performed via high-throughput immunoassay and was adjusted for demographic and clinical variables. sNfL levels >97.5^th percentile in healthy controls were considered elevated.

Among the MS patients eligible for analysis (n=3,705), 615 (16.6%) participants displayed elevated sNfL levels at baseline. The prospective assessment showed that elevated sNfL levels were associated with higher rates of longitudinal brain atrophy, as measured by brain parenchymal MRI fraction (elevated sNfL annualised change 0.27% vs normal sNfL 0.16%; P<0.001). This result was consistent across disease subtypes, and age and sex stratification. Furthermore, elevated sNfL was related to an increased risk of developing new T2 lesions (OR 1.90; 95% CI 1.43–2.51; P<0.001). This finding was significant across the pre-defined subgroups.

Prof. Jens Kuhle (University Hospital Basel, Switzerland) argued that the routine use of sNfL measurement in clinical practice is approaching. “At the moment, normative data from a general population is being analysed to enable the differentiation between pathological and physiological (i.e. age- or-BMI related) changes of sNfL levels.” He added that a recent study has shown that fixed cut-off points lead to false negatives and false positives in young and old patients with MS, respectively [4]. According to Prof. Kuhle, a personalised approach of sNfL measurement, including factors such as disease duration, Expanded Disability Status Scale (EDSS) score, treatment type, and the number of contrast-enhancing lesions shows promising results in an ongoing trial at the University of Basel. Moreover, an internet-based application to calculate sNfL Z-scores is under development, supporting the use of sNfL measures in clinical practice. On a more critical note, Prof. Kuhle mentioned that pre-clinical studies should provide more insight regarding NfL metabolism and kinetics and that standardisation of sNfL measurement is needed to create a uniform tool to use in clinical practice.

1. Sotirchos ES, et al. Serum Neurofilament Light Chain is Associated with Longitudinal Brain Atrophy and Radiological Disease Activity in the MS PATHS Network. OP088, ECTRIMS 2021 Virtual Congress, 13–15 October.
2. Kuhle J. Neurofilaments: ready for routine clinical use? OP085, ECTRIMS 2021 Virtual Congress, 13–15 October.
3. Kuhle J, et al. Mult Scler. 2016;22(12):1550–1559.
4. Kuhle J, et al. Neurology. 2019;92(10)e1007–e1015.

 

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Posted on 9 December, 20219 December, 2021