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Serum NfL as biomarker for suboptimal treatment response

MS Virtual 2020
Cohort study, Swiss MS
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.


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