Author Response: Serum Neurofilament Light Association With Progression in Natalizumab-Treated Patients With Relapsing-Remitting Multiple Sclerosis

We are grateful for the interest in our study.¹ We did not conclude that serum neurofilament light chain (sNfL) is not a valid biomarker for disease progression. Rather, we indicated that it may not be well suited to monitor or predict progression in people with relapsing-remitting multiple sclerosis (RRMS) treated with natalizumab. At least 2 reasons may explain the discrepancy between our findings and those reported by Kropshofer et al.² First, the population we investigated consisted exclusively of people with RRMS, as opposed to people with secondary progressive multiple sclerosis in the EXPAND study.³ The rate of progression differs greatly between these 2 populations, and prediction of progression in people with RRMS may require more sensitive tools. Second, in our study, all patients were treated with natalizumab, which silences acute focal inflammatory disease activity in a vast majority of patients compared with placebo.⁴ In the EXPAND study, 43% of the siponimod-treated patients had new or enlarging T2 lesions during the 24 months follow-up.³ Thus, siponimod-treated patients are less well suited to investigate the biological underpinnings of progression because of residual focal inflammatory disease activity. We contend that larger studies investigating natalizumab and/or ocrelizumab patients are needed to determine the prognostic and monitoring potential of sNfL in terms of progression.