Serum NfL as biomarker for suboptimal treatment response

Serum neurofilament light chain (sNfL) levels are independently associated with clinical and MRI measures of MS disease activity in MS patients [1]. Increased sNfL in patients on disease-modifying therapies for at least 3 months therapy predicted relapses, EDSS worsening, and MRI activity in the subsequent year. Current sNfL levels predicted future clinical disease activity, can detect subclinical disease activity in NEDA-3 patients and may serve as independent of standard metrics for treatment monitoring, and can detect subclinical disease activity in NEDA-3 patients.

Participants were 1,062 patients from the Swiss MS Cohort Study, of whom 95.9% had relapsing-remitting MS and 4.1% clinically isolated syndrome (CIS). Median age was 39.7 years, median EDSS 2.0, and median follow-up 5 years. All patients were on disease-modifying therapy for at least 3 months. sNfL was measured every 6 or 12 months with the NF-light^® assay. A total of 5,192 longitudinal samples were analysed and compared with 8,865 samples of healthy controls.

Clinical events (EDSS worsening or relapse; n=4,624) in the following year were predicted by the sNfL z-score (OR 1.21; P<0.001). There was a “dose-effect relationship” with increasing sNfL z-score (see Figure). Results for the prediction of future new/enlarging T2 lesions and brain volume loss were similar. In a multivariable mixed logistic regression model, new/enlarging T2 lesions (OR 1.88; P=0.016) and sNfL z-score >1.5 (OR 2.18; P=0.009) predicted future clinical events (n=853); previous EDSS worsening, previous relapses and current contrast enhancement did not. Even in NEDA-3 patients, change of sNfL z-score could predict clinical events (relapses, EDSS worsening, contrast enhancing or new/enlarging T2 lesions in brain MRI; n=587) in the subsequent year (OR 1.37; P=0.025).

Figure: sNfL z-score predicts relapse or EDSS-worsening in the following year [1]

These study results in a well-characterised, large, real-world cohort support the use of sNfL to monitor treatment effects in MS clinical practice. According to the authors, sNfL gives a unique signal that is not captured by other markers.

1. Yaldizli Ö, et al. Value of serum neurofilament light chain levels as a biomarker of suboptimal treatment response in MS clinical practice. MSVirtual 2020, Abstract PS09.05.