ObjectiveTo evaluate the use of CSF neurofilament light chain (NfL) measurements in clinical practice as well as their effect on treatment strategies and outcomes in patients with MS.MethodsThis was an observational cohort study of patients with MS who had a CSF NfL measurement between December 2015 and July 2018 as part of their routine clinical care. Treatment strategies were classified as “No Treatment/No Escalation” (no treatment or no escalation of treatment) or “Treatment/Escalation” (first-line injectable/oral disease-modifying therapies (DMTs), highly active DMTs, or treatment escalation). Change in Expanded Disability Status Scale (EDSS) scores was evaluated after 1-year follow-up.ResultsOf 203 patients with MS, 117 (58%) had relapsing-remitting MS. Disease activity was most frequently indicated by elevated CSF NfL (n = 85), followed by clinical (n = 81) and MRI activity (n = 65). CSF NfL measurements were independently associated with clinical (p= 0.02) and MRI activity (p< 0.001). Of those with elevated CSF NfL as the only evidence of disease activity (n = 22), 77% had progressive MS (PMS). In patients with PMS, 17 (20%) had elevated CSF NfL as the sole indicator of disease activity. Elevated CSF NfL resulted more frequently in Treatment/Escalation than normal CSF NfL (p< 0.001). Median EDSS change at follow-up was similar between patients receiving No Treatment/No Escalation and Treatment/Escalation decisions (p= 0.81).ConclusionsCSF NfL measurements informed treatment strategies, alongside clinical and MRI measures. CSF NfL levels were the only indicator of disease activity in a subset of patients, which was more pronounced in patients with PMS. Elevated CSF NfL was associated with more Treatment/Escalation strategies, which had an impact on EDSS outcomes at 1 year.