*Article* **Longitudinal Serum Neurofilament Levels of Multiple Sclerosis Patients Before and After Treatment with First-Line Immunomodulatory Therapies**

#### **André Huss 1, Makbule Senel 1, Ahmed Abdelhak 1,2,3, Benjamin Mayer 4, Jan Kassubek 1, Albert C. Ludolph 1, Markus Otto 1 and Hayrettin Tumani 1,5,\***


Received: 9 July 2020; Accepted: 25 August 2020; Published: 28 August 2020

**Abstract:** Serum neurofilament light chain (NfL) has been shown to correlate with neuroaxonal damage in multiple sclerosis (MS) and various other neurological diseases. While serum NfL is now regularly reported in clinical approval studies, there is a lack of longitudinal data from patients treated with established basic immunotherapies outside of study conditions. In total, 34 patients with early relapsing-remitting MS (RRMS) were included. The follow-up period was 24 months with regular follow-up visits after 3, 6, 9, 12 and 18 months. Therapy with glatiramer acetate was initiated in 20 patients and with interferon-beta in 12 patients. The disease course was monitored by the events of relapses, Expanded Disability Status Scale (EDSS) score and MRI parameters. Overall, serum NfL levels were higher at time points with a current relapse event than at time points without relapse (12.8 pg/mL vs. 9.7 pg/mL, *p* = 0.011). At follow-up, relapse-free patients showed significantly reduced serum NfL levels starting from 9 months compared to baseline (*p* < 0.05) and reduced levels after 12 months compared to baseline (*p* = 0.013) in patients without EDSS progression for 12 months. In this explorative observational study, our data sugges<sup>t</sup> that the longitudinal measurement of serum NfL may be useful in addition to MRI to monitor disease activity and therapy response.

**Keywords:** multiple sclerosis; serum neurofilament; immunomodulatory therapies; therapy-response marker
