Serum neurofilament light (NfL), a marker of neuronal injury, was tied to multiple sclerosis (MS) disability, brain atrophy, and disease activity, a large real-world study showed.
Among nearly 7,000 MS patients, those with elevated serum NfL had worse walking speed, manual dexterity, and processing speed; lower whole brain and thalamic volumes; and higher number of gadolinium-enhancing lesions (P<0.001 for all), reported Elias Sotirchos, MD, of Johns Hopkins University in Baltimore.
The findings were presented at a scientific session at ACTRIMS Forum 2021, the annual meeting of the Americas Committee for Treatment and Research in Multiple Sclerosis.
This is one of the largest studies to assess serum NfL in MS, Sotirchos noted. “Evaluations of serum NfL in large heterogeneous populations of people with MS are limited,” he said.
“It’s important to characterize the effects of demographics, comorbid conditions, lifestyle factors, and MS clinical characteristics on serum NfL levels, as well as to perform large-scale clinical validation of serum NfL” before it could be used as a biomarker of MS in clinical practice, Sotirchos told MedPage Today.
The cross-sectional analysis showed not only that NfL was linked with signs of disease progression, but that diabetes, smoking, or BMI may affect NfL levels. “This supports that these factors need to be accounted for” when constructing reference ranges to avoid misinterpretation of serum NfL values, Sotirchos pointed out.
Neurofilament light is being studied as a possible biomarker in several neurodegenerative disorders, including Alzheimer’s disease and Guillain-Barré syndrome. “Serum NfL is a marker of axonal damage and is not specific to MS,” observed Tanuja Chitnis, MD, of Harvard Medical School in Boston, who wasn’t involved with the study.
“In MS, elevated serum NfL levels are associated with new MRI lesions in the short-term and are modestly associated with brain atrophy in the longer term,” Chitnis told MedPage Today. “Serum NfL may be useful in monitoring response to disease modifying treatments in MS patients.”
The study incorporated questionnaire data and electronic health records from 6,968 patients in MS PATHS, a network of healthcare institutions in the U.S. and Europe. MS patients had an average age of 48; 72% were women and 80% were white. Most (62.1%) had relapsing-remitting MS. Median disease duration was 13 years.
The analysis also inclueded 201 healthy controls who were age 43 on average; 74% were women and 84% were white. The researchers derived age-specific cutoffs from healthy control data, defining the 97.5th percentile as the threshold for elevated NfL.
In total, 1,202 MS patients (17.2%) had elevated serum NfL. Factors associated with elevated NfL included progressive MS (OR 1.63, 95% CI 1.38-1.92), non-white race (OR 1.43, 95% CI 1.17-1.74), diabetes (OR 1.89, 95% CI 1.42-2.49), and smoking status (current vs never smoker OR 1.49, 95% CI 1.20-1.85). Age and symptom duration showed complex associations with serum NfL status, Sotirchos said, but the highest frequency of elevated NfL overall was seen in younger patients with shorter disease duration.
Higher BMI was associated with lower odds of elevated serum NfL (OR 0.83 per 5 kg/m2 increase, 95% CI 0.78-0.88). This inverse association also was reported in another recent study, Sotirchos noted.
Follow-up assessments of the MS PATHS cohort are ongoing, he added. Planned analyses include comparisons of serial NfL with longitudinal clinical and MRI outcomes.
Disclosures
MS PATHS is supported by Biogen.
Sotirchos disclosed relevant relationships with Alexion, Viela Bio, Genentech, and Biogen.