In patients who experienced a first clinical demyelinating event, baseline levels of serum neurofilament light chain (sNfL), a biomarker of neural damage, were associated with conversion to McDonald 2005 multiple sclerosis (MS). This was assessed in a post-hoc analysis of the phase 3 REFLEX trial. Age, multifocal disease, and the amount of T1 or T2 lesions at baseline predicted conversion to definite MS as well.


sNfL is a known biomarker to evaluate therapy effectiveness and disease activity in MS patients. The phase three REFLEX trial (NCT00404352) showed that treatment with subcutaneous interferon-beta-1a (scIFNβ-1a) delayed the onset of McDonald 2005 MS in patients with a first clinical demyelinating event. This treatment also reduced sNfL levels from 6 months post-baseline. The current post-hoc analysis of this trial analysed whether baseline sNfL levels in patients treated with scIFNβ-1a could predict the onset of McDonald 2005 MS. Results were presented by Prof. Jens Kuhle (University of Basel, Switzerland). A two-year follow up of patients in the scIFNβ-1a thrice-weekly (n=171), once-weekly (n=175), and placebo (n=171) groups showed that baseline levels of sNfL predicted the conversion to McDonald 2005 MS in all groups. Patients with high sNfL levels at baseline (>26.1 μg/mL) have an increased risk of developing definite MS within a 2-year timeframe. sNfL subgroup analysis demonstrated that treatment with scIFNβ-1a delayed MS onset in both patients with low and high baseline levels of sNfL. Other findings from this study demonstrated that a younger age, multifocal first clinical demyelinating event, and the number of T1 and T2 lesions predicted the onset of definite MS in all groups of the REFLEX trial.


  1. Kuhle J, et al. Baseline Serum Neurofilament Light Chain Levels Predict Conversion to McDonald 2005 Multiple Sclerosis (MS) Within 2 Years of a First Clinical Demyelinating Event in Patients with MS. P5.080, AAN 2021 Virtual Congress, 17-22 April.