Serum neurofilament light: A biomarker for disease activity in MS

ECTRIMS 2018

Serum neurofilament light: A biomarker for disease activity in MS

1920 1080 Mea Holm, PhD

How close are we to establishing a reliable liquid biomarker for detecting disease onset, progression and treatment response in multiple sclerosis? According to Dr Peter Calabresi (Johns Hopkins, USA) at ECTRIMS 2018, we are not far from implementing neurofilament light (NfL) into clinical care as a predictive biomarker of neuronal damage in MS.

Dr Calabresi presented the results of a study aimed at identifying the relevant serum NfL levels for stratifying disease severity and treatment responses in patients with relapsing-remitting MS (RRMS). A total of 1,464 serum samples were collected from patients enrolled in four phase III clinical trials: ADVANCE (n=859 samples), CHAMPS (n=319 samples), MSCRG (n=164 samples), and SENTINEL (n=122 samples). NfL levels were measured using the SIMOA assay and correlated with disease outcomes.

Results showed that serum NfL levels above 16 pg/mL were indicative of high disease activity, whereas levels below 8 pg/mL were associated with lower activity. Patients were, therefore, placed into three groups according to their NfL level – low (<8 pg/mL), intermediate (8–16 pg/mL) and high (>16 pg/mL). The corresponding NfL levels at baseline were found to correlate significantly with a) the number of MRI-detected lesions at baseline, b) the volume of MRI lesions 5 and 10 years later, and c) the rate of brain atrophy 5 years later. In addition, patients with consistently high NfL levels at repeated time points had an increased probability of developing new lesions and experiencing greater brain atrophy over the next four years. Dr Calabresi emphasised the importance of measuring NfL levels repeatedly to improve the predictive power of this disease activity biomarker.

What about treatment response? Patients on highly effective disease-modifying therapies (DMTs) experienced a decrease in serum NfL levels. The proportion of patients with high NfL levels (>16 pg/mL) decreased from 25% to 10% on treatment with pegylated interferon-ß (ADVANCE study), and from 30% to 4% on treatment with natalizumab (SENTINEL study).

Researchers hope that these promising results will be a step in the evolution of serum NfL from an experimental approach to a robust, standardised and clinically applicable biomarker for MS disease activity and progression. Because NfL levels are not specific to MS, but rather associated with overall neuronal damage, NfL may well serve as a general biomarker for other neurological diseases.


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