Neurofilament Light Prognostic Value in MS Is Limited on Individual Level

August 13, 2019

Although the biomarker was associated with disease activity, its prognostic value on the individual patient level is still limited per these 10-year data of more than 600 patients with multiple sclerosis.

Ester Cantó, PhD

Recent study results showed serum neurofilament light (NfL) chain levels increased significantly faster in patients with multiple sclerosis (MS) who were experiencing disability worsening than those who were clinically stable, though the biomarker was not predictive of future disease progression or relapse.

The findings strengthen the argument in favor of NfL as a biomarker of disease activity in MS, though its prognostic value on the individual level is still limited per these data, wrote Ester Cantó, PhD, of the Weill Institute for Neurosciences, University of California San Francisco, and colleagues. Serum NfL levels were associated with brain fraction loss, however

At baseline, the serum NfL levels showed significant associations with a number of factors, including Expanded Disability Status Scale (EDSS) scores (β, 1.080; 95% CI, 1.047—1.114; P&thinsp;<.001), MS subtype (β, 1.478; 95% CI, 1.279—1.707; P&thinsp;<.001), and treatment status (β, 1.120; 95% CI, 1.007-1.245; P&thinsp;=&thinsp;.04).

“[In the long-term,] we were also unable to replicate the finding that levels of [serum] NfL are associated with future EDSS worsening,” Cantó and colleagues noted. “Possible explanations for these discrepancies may be unidentified confounders inherent to each data set, the lack of a healthy control data set in our study for calculating the sNFL percentiles, or therapeutic practices that could attenuate sNFL levels as well as clinical outcomes.”

The investigators wrote that this data, however, is representative of the long-term variability that is inherent in MS, with the lack of association found possibly due to the lag in evolution of disability after neuronal injury.

“On the other hand, we show for the first time, to our knowledge, that participants who experienced disability worsening as measured by a clinically significant increase in EDSS have a different rate of [serum] NfL change over time compared with those not showing worsening,” they detailed.

Overall, the study included 607 patients with MS over a 12-year period (median follow-up, 10 years; interquartile range, 7—11 years), with 3904 quality-assured samples. At 5 years follow-up, active treatment was linked to lower serum NfL levels (ß, 0.946; 95% CI, 0.915–0.976; P <.001), and higher potency therapies were associated with greater decreases in their levels compared with platform treatments (ß, 0.972; 95% CI, 0.948—0.998; P&thinsp;=&thinsp;.04).

Based on area under the curve (AUC) values, baseline NfL levels were not associated with subsequent clinical relapses (AUC range, 0.59—0.72). Although higher levels were associated with a greater risk of relapse In the 60 days and 1 year prior to sampling, extreme levels were not associated with future relapse. Likewise, NfL levels were not associated with long-term disability (AUC range, 0.54–0.59).

At year 10, only baseline serum NfL levels were linked with approximately 11.6% of brain fraction atrophy variance. When considering sex, age, and disease duration in multivariable analysis, these baseline levels were associated with 18.0% of the variance in brain fraction atrophy. “We also observed a significantly different atrophy rate over time between patients with serum NfL levels greater than and less than established percentiles, further supporting the potential of serum NfL levels as biomarkers of brain damage,” Cantó and colleagues wrote.

When restricting the analysis to patients who began With relapsing MS or clinically isolated syndrome (n = 372), T2 lesion volume was associated with NfL levels over time (β, 3.361; 95% CI, 2.300—4.420; P&thinsp;=&thinsp;5.8×10−10). As well, there was an association between serum NfL levels and brain fraction (β, 2.0×10−4; 95% CI, 4×10−6—0.000396; P&thinsp;=&thinsp;.02). These links remained significant when adjusted. Upon stratifying patients into extreme percentiles at baseline, there was also an interaction between percentile and time (β,&thinsp;0.00028; 95% CI, 0.00014—0.00042; P&thinsp;<.001).

“Our findings from a large observational cohort followed up for 12 years at a single center suggest that sNFL levels are associated with brain atrophy, changes in [serum] NfL levels are associated with disability worsening, and [serum] NfL levels may be influenced by treatment,” the investigators concluded.


Canto E, Brro 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. JAMA Neurol. Published online August 12, 2019. doi: 10.1001/jamaneurol.2019.2137.