Prognostic Value of Serum Neurofilament Light Chain for Disease Activity in Patients with Relapsing Multiple Sclerosis: Results from Subgroup Analysis Based on Body Mass Index and Age from the Phase 3 ASCLEPIOS I/II Trials
Anne Cross1, Tjalf Ziemssen2, Douglas Arnold3, Eric Thouvenot4, Scott Zamvil5, Alit Bhatt6, Wenjia Wei7, Ibolya Boer7, Enrique Alvarez8, Heinz Wiendl9
1Washington University School of Medicine, Saint Louis, MO, USA, 2Center of Clinical Neuroscience, Department of Neurology, University Clinic Carl-Gustav Carus, Dresden, Germany, 3Brain Imaging Centre, Montreal Neurological Institute and Hospital, McGill University, Montreal, Quebec, Canada, 4Department of Neurology, Centre Hospitalier Universitaire (CHU) Nîmes, University of Montpellier, Nîmes, France; Institut de Génomique Fonctionnelle, UMR, Institut National de la Santé et de la Recherche Médicale (INSERM), University of Montpellier, Montpellier, France, 5UCSF Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, CA, USA, 6Novartis Healthcare Pvt. Ltd., Hyderabad, India, 7Novartis Pharma AG, Basel, Switzerland, 8Department of Neurology, Rocky Mountain MS Center at the University of Colorado, Aurora, CO, USA, 9University of Münster, Münster, Germany
Objective:

To evaluate the prognostic value of serum neurofilament light chain (sNfL) for future disease activity according to body mass index (BMI) and age in people with relapsing multiple sclerosis (pwRMS).

Background:

In the Phase 3 ASCLEPIOS I/II trials (ofatumumab versus teriflunomide [pwRMS aged 18–55]), sNfL levels were prognostic for on-study lesion formation and brain volume loss in the overall and recently diagnosed treatment-naive populations. Age and BMI may affect sNfL levels.

Design/Methods:

A baseline sNfL cut-off was predefined by the median sNfL value across ASCLEPIOS I/II and participants were stratified into high (≥median [9.3 pg/mL]) and low (<9.3 pg/mL) groups, irrespective of treatment received. The prognostic value of high versus low baseline sNfL for the annualized rate of new/enlarging T2 (neT2) lesions was assessed in baseline BMI [<24.5 versus ≥24.5 kg/m2] and age [<38 versus ≥38 years] subgroups. Negative binomial regression model adjusting for sNfL group, and sNfL group by BMI/age subgroup interaction, were used to estimate the lesion rate ratio (RR) for high versus low sNfL levels in each BMI/age subgroup.

Results:

Of the 1,882 participants randomized in ASCLEPIOS I/II, 1,678 (89.2%) had baseline sNfL and neT2 data available. In both BMI subgroups (<24.5 and ≥24.5 kg/m2), participants with high versus low sNfL had a higher mean annualized rate of neT2 lesions (BMI <24.5: 4.04 versus 2.10, RR: 1.92; BMI ≥24.5: 4.14 versus 1.66, RR: 2.49; p<0.001 for both). In both age subgroups (<38 and ≥38 years), participants with high versus low sNfL had a higher mean annualized rate of neT2 lesions (<38: 5.68 versus 2.91, RR: 1.95; ≥38: 2.50 versus 0.94, RR: 2.66; p<0.001 for both).

Conclusions:

Baseline sNfL levels were prognostic of future lesion formation irrespective of baseline BMI and age, supporting the use of sNfL as a prognostic biomarker for RMS disease activity.

10.1212/WNL.0000000000206068