To assess cross-sectional associations with neurofilament light (NfL) levels at baseline in relapsing multiple sclerosis (RMS) and primary progressive MS (PPMS).

NfL is a structural neuroaxonal protein released upon neuronal injury into the cerebrospinal fluid and blood independent of causal pathways. NfL may be a prognostic biomarker in MS.  

 Serum NfL concentrations were measured in 2 trials, including OPERA I in patients with RMS (ocrelizumab [OCR] vs interferon β-1a; n=716) and ORATORIO in patients with PPMS (OCR vs placebo; n=517), using the Quanterix NfL Advantage kit. Clinical and/or demographic covariates were examined for cross-sectional associations with NfL levels at baseline in each trial. 

Multivariate analysis identified higher gadolidium (Gd)-enhancing lesion counts (RMS, p<0.001; PPMS, p<0.001) and higher T2 lesion volumes (RMS, p<0.001; PPMS, p=0.002) in scans obtained at trial entry as most strongly associated with abnormally increased baseline NfL levels. Shorter clinical disease duration (RMS, p<0.001; PPMS, p=0.021) and lower body weight (RMS, p=0.035; PPMS, p<0.001) at trial entry were also significantly associated with baseline NfL in both populations. Shorter time since last relapse at trial entry was independently associated with increased baseline NfL concentrations in RMS (p=0.002). Older age (RMS, p=0.83; PPMS, p=0.016) and higher baseline Expanded Disability Status Scale score (RMS, p=0.41; PPMS, p=0.038) showed nominal associations with increased NfL levels at trial entry for PPMS only in univariate analyses.

Factors independently associated with higher serum NfL levels in RMS and PPMS at baseline included higher number of Gd-enhancing lesions, higher T2 lesion volume, shorter disease duration and lower body weight. These baseline factors should be considered as possible sources of abnormally high NfL concentrations when NfL levels are examined for prognostication of disability course or measuring treatment response in MS.