Using Serum Neurofilament Light Chains as a Biomarker of MS Disease Activity

Serum neurofilament light chain (sNFL) is associated with brain atrophy and disability worsening, which means it can be used as an objective surrogate of ongoing disease activity in multiple sclerosis (MS), according to research published in JAMA Neurology.

Currently, decisions about who to treat, how long to treat them, and when to change therapy are all based on tolerability of treatment and presumptions of long-term efficacy. “The lack of sensitive laboratory measures of worsening, progression, and treatment response represent an important unmet need,” the authors explained.

The authors studied 607 patients with MS from the EPIC (Expression, Proteomics, Imaging, Clinical) study that took place at the University of California, San Francisco between July 1, 2004 and August 31, 2017. For 5 years, clinical evaluations and sample collections were performed annually, then at different time points for up to 12 years. There was a median follow-up duration of 10 years.

The majority of patients (n = 435, 71.6%) had relapsing-remitting MS, followed by clinically isolated syndrome (n = 93, 15.3%), secondary progressive MS (n = 54, 8.9%), and primary progressive MS (n = 25, 4.1%). The median baseline sNFL concentration was 25.5 pg/mL, and the levels were positively associated with age. Baseline sNFL levels were also associated with Expanded Disability Status Score, with higher sNFL levels associated with more disability.

Baseline sNFL levels were associated with a relapse in the 90 days before sampling and treatment status. When participants were separated into inactive (no relapses from baseline to year 5) or active (1 or more relapses), the researchers noted that activate participants had significantly higher levels of sNFL at baseline. Similarly, when patients were separated into those who experienced worsening disability from years 4 to 6 versus those who did not experience worsening, the researchers found that sNFL levels increased steeply among patients with worsening. However, there was no difference at sNFL levels at baseline.

When looking at sNFL levels after treatment, the researchers found that active treatment was associated with lower levels of sNFL after 5 years’ follow-up and high-potency treatments were associated with greater decreases in sNFL levels compared with platform therapies.

“The potential of sNFL to serve as a surveillance biomarker for treatment response should be further defined by including sNFL levels as an outcome in treatment-specific clinical trials,” the authors noted.

Reference

Cantó E, Barro C, Zhao C, et al. Association between serum neurofilament light chain levels and long-term disease course among patients with multiple sclerosis followed up for 12 years [published online August 12, 2019]. JAMA Neurol. doi: 10.1001/jamaneurol.2019.2137.