NfL z score less than or equal to 1 or greater than 1 was used as a time-varying covariate, either at CDW-NR(−1) or CDW-NR(−2), correcting for age, sex, disease course (relapsing vs progressive multiple sclerosis [MS]), disease-modifying treatment (DMT) category (high-efficacy monoclonal antibodies, oral DMT, platform DMT, and untreated), recent relapse (within 90 days) at measurement visit, and Expanded Disability Status Scale (EDSS) at baseline. NfL z score was associated with higher risk for future CDW-NR at visits CDW-NR(−1) in the Expression, Proteomics, Imaging, Clinical (EPIC) study (B) and CDW-NR(−2) in Swiss Multiple Sclerosis Cohort (SMSC) (C). NfL z scores at visits closest to the event, CDW-NR(−1) in SMSC (A), or too distant from the event, CDW-NR(−2) in EPIC (D), were not significantly associated with CDW-NR. aHR indicates adjusted hazard ratio.