Temporal profile of serum neurofilament light in multiple sclerosis: Implications for patient monitoring

Peter A Calabresi, Douglas L Arnold, Dipen Sangurdekar, Carol M Singh, Arman Altincatal, Carl de Moor, Bob Engle, Jaya Goyal, Aaron Deykin, Suzanne Szak, Bernd C Kieseier, Richard A Rudick, Tatiana Plavina, Peter A Calabresi, Douglas L Arnold, Dipen Sangurdekar, Carol M Singh, Arman Altincatal, Carl de Moor, Bob Engle, Jaya Goyal, Aaron Deykin, Suzanne Szak, Bernd C Kieseier, Richard A Rudick, Tatiana Plavina

Abstract

Objective: To understand how longitudinal serum neurofilament light chain (sNfL) patterns can inform its use as a prognostic biomarker in multiple sclerosis (MS) and evaluate whether sNfL reflects MS disease activity and disease-modifying therapy usage.

Methods: This was a post hoc analysis of longitudinal data and samples from the ADVANCE trial (NCT00906399) of patients with relapsing-remitting MS (RRMS). sNfL was measured every 3 months for 2 years, then every 6 months for 4 years. Regression models explored how sNfL data predicted 4-year values of brain volume, expanded disability status scale score, and T2 lesions. sNfL levels were assessed in those receiving placebo, peginterferon beta-1a, and those with disease activity.

Results: Baseline sNfL was a predictor of 4-year brain atrophy and development of new T2 lesions. Clinical (p = 0.02) and magnetic resonance imaging (MRI) (p < 0.01) outcomes improved in those receiving peginterferon beta-1a whose sNfL decreased to <16 pg/mL after 12 months versus those whose sNfL remained ⩾16 pg/mL. Mean sNfL levels decreased in peginterferon beta-1a-treated patients and increased in placebo-treated patients (-9.5% vs. 6.8%; p < 0.01). sNfL was higher and more variable in patients with evidence of active MS.

Conclusion: These data support sNfL as a prognostic and disease-monitoring biomarker for RRMS.

Keywords: Biomarker; brain atrophy; magnetic resonance imaging; multiple sclerosis; prognosis; serum neurofilament light chain.

Conflict of interest statement

Declaration of Conflicting Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: P.A.C. received consulting fees from Biogen and Disarm and grants from Annexon and Biogen. D.L.A. reports equity interest in NeuroRx during the conduct of the study and consulting activities with Biogen, Celgene, Frequency, Genentech, GeNeuro, Genzyme, MedImmune, Merck Serono, Novartis, Receptos, Roche, and Sanofi-Aventis, and received grants from Biogen, Immunotec, and Novartis. D.S., J.G., and T.P. were employees of Biogen at the time of this study. C.M.S., A.A., C.d.M., B.E., A.D., S.S., B.C.K., and R.A.R. are employees of and hold stock/stock options in Biogen.

Figures

Figure 1.
Figure 1.
sNfL levels across time in patients classified as exhibiting NEDA or EDA: (a) patients classified as exhibiting NEDA for the entire duration of the study, n = 65 (NEDA for 4 years) and (b) patients classified as exhibiting EDA at any time during the study,n = 832 (EDA over 4 years). The average annualized PBVC is based on data collected at 6 months and at 1, 2, 3, and 4 years. Each line represents the sNfL data for an individual patient. CV: coefficient of variation; EDA: evidence of disease activity; NEDA: no evidence of disease activity; PBVC: percent brain volume change; sNfL: serum neurofilament light chain.
Figure 2.
Figure 2.
sNfL levels measured at baseline and 48 weeks. (a) Placebo,n = 373. (b) Peginterferon beta-1a cohorts,n = 350. sNfL: serum neurofilament light chain. Dotted horizontal lines indicate 16 pg/mL, which we consider to be the threshold for active MS disease.

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