To assess the utility of sNfL levels in a diverse MS population on variable efficacy DMTs.

Serum neurofilament light chain (sNfL) has been established as a biomarker for disease activity in multiple sclerosis (MS) research. Impact of sNfL in clinical practice, with older population, multiple comorbidities, and variable efficacy disease modifying therapies (DMTs), has not yet been established.

Retrospective chart extraction of MS patients seen at our clinic with one or more sNfL levels drawn was completed. DMTs were classified as low efficacy (LeDMT: teriflunomide, fumarates, interferons, glatiramer acetate), moderate (MeDMT: S1P modulators, cladribine), high (HeDMT: B-cell therapy, natalizumab), and no DMT. Patients with highest sNfL values on HeDMT were further reviewed.

662 patients were identified, with 72.6% females and mean age 52 years (20-81). 67.5% of all patients were on HeDMT, and had average sNfL level of 1.9 pg/ml (0.2-19.6); MeDMT 1.7 pg/ml (0.7-3.4); LeDMTs 2.2 pg/ml (0.6-7.3); no DMT 3.04 pg/ml (0.3-30.7). Among patients on B-cell therapies, rituximab showed lowest average sNfL level of 1.81 pg/ml and ublituximab highest at 2.06 pg/ml. Twelve patients with highest sNfL levels on HeDMT were reviewed further (top 3rd percentile, 5.2-19.6). They had average disease duration of 15 years (1-35) with 3.8 years (0.1-7.9) on HeDMT, prior to which they were on LeDMT or no DMT. The patient with sNfL level of 19.6 pg/ml had confounding diabetes with HbA1C 9.2%. 83.3% of these patients had moderate-high disease burden on MRI brain, 66.7% had cervical lesions and 16.7% had both cervical and thoracic lesions. 

sNfL levels correlate with efficacy of DMTs and potentially the duration of therapy. Patients with high sNfL levels despite HeDMT, have high MRI disease burden, potentially requiring closer monitoring. Comorbidities and variable test techniques limit the generalisability of sNfL in current clinical practice.