Correlation with outcomes
At the group level, patients with MS have higher levels of NfL, compared with controls, and levels are higher in patients with progressive forms of MS versus relapsing forms. “Levels increase dramatically in the wake of relapse,” he said.
Barro et al. found that patients with higher serum levels of NfL are more likely to experience Expanded Disability Status Scale (EDSS) worsening (Brain. 2018 Aug 1;141:2382-91). Furthermore, MRI lesions are independently associated with serum NfL, and patients with higher levels of serum NfL have significantly greater average loss in brain volume and spinal cord volume over 5 years.
A treatment algorithm
NfL someday could be incorporated into MS treatment algorithms, Dr. Leppert suggested. For instance, if a patient has high levels of disease activity based on MRI or clinical grounds, then prescribe a high-efficacy therapy. If not, measure NfL. “If the levels are low, then you can be assured to use platform therapies or continue what the patient has. But if NfL levels are high, then you should choose high efficacious therapies or switch to high-efficacious therapies in the long run,” he said.
Limitations and next steps
Although NfL is a specific marker of neuronal damage, it is not specific for the cause of the damage. Further studies are needed to better understand NfL metabolism and confounding factors such as age. Reference biomarkers likely will be needed “to conceptualize whether the signal of NfL is due to acute disease or chronic disease,” Dr. Leppert said.
“We need to optimize the assay and come to a worldwide agreement on the platform. We need to have prospective studies, mainly to achieve regulatory acceptance. And we need to have a normative database” to determine which NfL values are pathologic at a particular age, he said.
Despite the biomarker’s potential, blood NfL levels will not replace clinical expertise. “Biomarkers cannot be of value without a clinical backing and a clinical evaluation,” Dr. Leppert said. “The idea that this will replace us or any other person who makes a clinical judgment is a big error. NfL will prevail as a biomarker. ... But interpretation of the clinical background is germane.”
Dr. Leppert has been an employee of pharmaceutical companies, most recently Novartis.