Neurofilament Light Levels Predict Future MS Disease Activity Regardless of Race or Ethnicity

Silvia R. Delgado, MD

A post-hoc analysis of the phase 3 ASCLEPIOS I and II trials (NCT02792218; NCT02792231) showed that baseline serum neurofilament light (NfL) chain levels predicted future disease activity in all patients with relapsing multiple sclerosis (MS), including those of diverse racial/ethnic subpopulations.¹

Presented at the 2024 Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum, held February 29 to March 2, in West Palm Beach, Florida, the analysis included 1678 patients (89.2%) from the original cohort who had serum NfL and new/enlarging T2 lesion data available. Each patient was stratified into high (≥9.3 pg/mL) and low (<9.3 pg/mL) groups of NfL levels irrespective of treatment received and had new/enlarging T2 lesions analyzed at last available scan using a binomial model.

Led by Silvia R. Delgado, MD, a professor of neurology at the University of Miami Miller School of Medicine, the annualized mean rate of new/enlarging T2 lesions for those with high or low baseline serum NfL levels was 4.08 and 1.85, respectively, for the overall population. For those with high/low baseline NfL levels in the Asian (n = 31/29), Black (n = 29/26), and Other (n = 39/36) subgroups, investigators reported new/enlarging T2 lesion rates of 2.59/0.97 (rate ratio [RR], 2.68; P = .042), 5.10/2.04 (RR, 2.50; P = .061), and 7.79/3.07 (RR, 2.54; P = .029), respectively. For the Caucasian subgroup (n = 738/752), the values were 3.91/1.83 (RR, 2.14; P <.001).

Published in the New England Journal of Medicine in 2020, the ASCLEPIOS trials were 2 double-blind, double-dummy phase 3 studies that assessed the effects of ofatumumab (Kesimpta; Novartis), a subcutaneous anti-CD20 monoclonal antibody, and teriflunomide (Aubagio; Sanofi), an oral inhibitor of pyrimidine synthesis. All told, results showed that ofatumumab was associated with lower annualized relapse rates than teriflunomide. The annualized relapse rates in the ofatumumab and teriflunomide groups were 0.11 and 0.22, respectively, in trial 1 (difference, −0.11; 95% CI, −0.16 to −0.06; P <0.001) and 0.10 and 0.25 in trial 2 (difference, −0.15; 95% CI, −0.20 to −0.09; P <0.001).²

Previous research has shown that elevated circulating NfL levels correlate with and may be predictive of MS relapses and acute inflammatory disease activity typically identified as gadolinium-enhancing lesions or new/enlarging T2 hyperintense lesions on MRI, as well as measures of central nervous system injury including accelerated brain volume loss. Several studies have shown promising results as a short-term predictor of clinical outcomes and MRI changes up to 10 years later.

A 2020 paper investigated the prognostic value of serum NfL levels measured at an early-stage of MS for prediction of long-term clinical outcomes in a cohort followed up for more than 15 years, the longest follow-up to date. In total, 76 patients had a median follow-up of 18.9 years (range, 15.0-27.0). Participants with NfL levels less than 7.62 pg/mL were 4.3 times less likely to develop an Expanded Disability Status Scale (EDSS) score of at least 4 (P = .001) and 7.1 times less likely to develop progressive MS (P = .054).³

Additional data from that study revealed that those with the highest NfL levels (3rd-tertile, >13.2 pg/mL) progressed most rapidly with an EDSS annual rate of 0.16 (P = .004), remaining significant after adjustment for sex, age, and disease-modifying treatment (P = .022). The time-tertile interaction was statistically significant (P = .0031), indicating that the curves were significantly non-parallel.

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REFERENCES
1. Delgado SR, Alvarez E, Thouvenot E, et al. Baseline serum neurofilament light chain levels predict future disease activity irrespective of race/ethnicity: results from the phase 3 ASCLEPIOS I/II trials. Presented at: 2024 ACTRIMS Forum; Feb 29-March 2; West Palm Beach, FL. Abstract P036.
2. Hauser S:. Bar-Or A, Cohen JA, et al. Ofatumumab versus teriflunomide in multiple sclerosis. NEJM. 2020;383:546-557. doi:10.1056/NEJMoa1917246
3. Thebault S, Abdoli M, Fereshtehnejad SM, et al. Serum neurofilament light chain predicts long term clinical outcomes in multiple sclerosis. Nature. 2020;10:10381. doi:10.1038/s41598-020-67504-6