034 – Serum neurofilament light chain predicts long-term clinical outcomes in multiple sclerosis

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034 – Serum neurofilament light chain predicts long-term clinical outcomes in multiple sclerosis

Simon Thebault (1) – Mohammad Abdoli (1) – Seyed-Mohammad Fereshtehnejad (1) – Daniel Tessier (2) – Vincent Tabard-Cossa (2) – Mark Freedman (1)
University of Ottawa, The Ottawa Hospital, Ottawa, Canada (1) – University of Ottawa, Department of Physics, Ottawa, Canada (2)


Objective
With the availability of more powerful treatments for multiple sclerosis (MS), prognostic biomarkers are badly needed. Levels of neurofilament light chains (NfL) found in serum result from the destruction of central nervous system (CNS) axons in MS and correlate with the aggressiveness of the disease. Our objective is to evaluate the prognostic values of serum NfL levels obtained close to the time of MS onset with long-term clinical outcomes.
Methods
In this prospective cohort study, we identified patients with serum collected within 5 years of first MS symptom onset (baseline) with more than 15 years of clinical follow-up. Clinical course, treatments and Expanded Disability Status Scale (EDSS) were recorded longitudinally. Levels of serum NfL were quantified in the patients as well as non-inflammatory age- and sex-matched controls using digital immunoassay technology (SiMoA HD-1 Analyzer from Quanterix).

Results:
Sixty-seven patients fit the inclusion criteria with a median follow-up period of 17.4 years (range: 15.1-26.1). Median serum NfL levels were 39.8% higher in MS patients compared to the 37 controls (p=0.004). Patients reaching EDSS≥4 had 62.0% higher baseline levels compared to the patients who did not (p=0.0001). The best NfL cutoff value for predicting progression was 7.62 pg/mL; patients with NfL >7.62 pg/mL had 8.9-times higher risk of developing progressive MS during follow-up (p = 0.034, 95% CI:1.2-68.1). Patients with the highest NfL levels (3rd-tertile) progressed most rapidly with an EDSS annual rate of 0.16 (p=0.004), remaining significant even after adjustment for sex, age, and disease-modifying treatment (p=0.022).
Interpretation:
This study demonstrates that higher levels of serum NfL detected early in the disease are associated with poorer long-term clinical outcomes. These patients may benefit from a more aggressive initial approach to initial treatment.
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