Serum neurofilament light chain correlations in patients with a first clinical demyelinating event in the REFLEX study: a post hoc analysis

Abstract

Background: In REFLEX, subcutaneous interferon beta-1a (sc IFN β-1a) delayed the onset of multiple sclerosis (MS) in patients with a first clinical demyelinating event (FCDE).

Objectives: This post hoc analysis aimed to determine whether baseline serum neurofilament light (sNfL) chain can predict conversion to MS and whether correlations exist between baseline sNfL and magnetic resonance imaging (MRI) metrics.

Methods: sNfL was measured for 494 patients who received sc IFN β-1a 44 μg once weekly (qw; n = 168), three times weekly (tiw; n = 161), or placebo (n = 165) over 24 months. Median baseline sNfL (26.1 pg/mL) was used to define high/low sNfL subgroups. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox's proportional hazard model to determine factors influencing the risk of conversion to MS. Kaplan-Meier estimates calculated median time-to-conversion to MS (McDonald 2005 criteria) or clinically definite MS (CDMS; Poser criteria). Correlations between sNfL and MRI findings were assessed using Spearman's rank correlation coefficient (r).

Results: Multivariable models indicated that high baseline sNfL was associated with the likelihood of converting to MS and inversely to time-to-conversion (HR = 1.3, 95% CI: 1.03-1.64; p = 0.024). Significant additional factors affecting conversion to McDonald MS were on-study treatment (sc IFN β-1a/placebo; qw: HR = 0.59, 95% CI: 0.46-0.76; tiw: HR = 0.45, 95% CI: 0.34-0.59), classification of FCDE (monofocal/multifocal; HR = 0.69, 95% CI: 0.55-0.85), and most baseline imaging findings (T2 and T1 gadolinium-enhancing [Gd+] lesions; HR = 1.02, 95% CI: 1.01-1.03 and HR = 1.07, 95% CI: 1.03-1.11); all p ⩽ 0.001. Conversion to CDMS showed similar results. At month 24, sNfL was strongly correlated with a mean number of combined unique active (r = 0.71), new T2 (r = 0.72), and new T1 Gd+ (r = 0.60) lesions; weak correlations were observed between sNfL and clinical outcomes for all treatment groups.

Conclusion: Higher baseline sNfL was associated with an increased risk of MS conversion, a risk that was mitigated by treatment with sc IFN β-1a tiw.

Trial registration: ClinicalTrials.gov identifier: NCT00404352. Date registered: 28 November 2006.

Keywords: interferon beta-1a; multiple sclerosis; serum neurofilament light chain.

Figure 1.

Kaplan–Meier cumulative incidence curves for time to conversion to MS (McDonald 2005 criteria) or clinically definite MS (Poser criteria) by treatment group, for each baseline sNfL subgroup. (a) Time to conversion to MS (McDonald 2005 criteria). (i) Low baseline sNfL (⩽ median baseline value). (ii) High baseline sNfL (> median baseline value). (b) Time to conversion to clinically definite MS (Poser criteria). (i) Low baseline sNfL (⩽ median baseline value). (ii) High baseline sNfL (> median baseline value). CI, confidence interval; IFN, interferon; MS, multiple sclerosis; qw, once weekly; sc, subcutaneous; sc IFN β-1a, subcutaneous interferon beta-1a; sNfL, serum neurofilament light chain; tiw, three times weekly.