Higher Blood NfL Levels Predict Worse Disability Over Time in MS, Study Suggests

Higher blood levels of the neurofilament light chain (NfL) protein at diagnosis are predictive of worse disability over time in people with multiple sclerosis (MS), a large population study from Sweden suggests.

The study, “Plasma neurofilament light levels are associated with the risk of disability in multiple sclerosis,” was published in the journal Neurology.

When neurons become damaged, NfL protein is released; as such, NfL levels are commonly used as a marker for nervous system damage.

Previous research has suggested NfL as a prognostic biomarker in MS — however, most of these studies measured NfL levels in cerebrospinal fluid (CSF), the fluid that surrounds the brain and spinal cord. Because of its invasive nature, measuring NfL via a CSF sample is not feasible as a routine clinical test.

Other studies have shown that NfL levels in blood are closely related to levels in CSF, raising the possibility that blood NfL levels could have prognostic value in MS. However, whether these levels can predict long-term outcomes in MS has not been extensively evaluated.

“In a disease like MS that is so unpredictable and varies so much from one person to the next, having a noninvasive blood test like this could be very valuable, especially since treatments are most effective in the earliest stages of the disease,” Ali Manouchehrinia, PhD, of the Karolinska Institutet, Sweden, and a study co-author, said in a press release.

To address blood NfL as potential marker of likely disability worsening over time (a prognostic marker), researchers measured blood NfL levels in 4,385 people with MS, including 3,664 with relapsing-remitting MS (RRMS), 511 with secondary progressive MS (SPMS), and 129 with primary progressive MS (PPMS). The remaining 81 individuals did not have their MS type recorded in the data analyzed.

For comparison, NfL levels were measured in 1,026 people without MS (a control group), who were similar to the MS group in terms of age and sex.

Results showed that blood NfL levels varied significantly with age in all groups. After adjusting for this, NfL levels were significantly higher in all MS groups than in controls — the median NfL levels were 8.5 picograms (pg)/mL in controls, and 17.1 pg/mL in RRMS patients, 18.4 pg/mL in those with SPMS, and 14.7 pg/mL in PPMS patients.

Researchers then calculated whether higher NfL levels were predictive of worsening disability, as assessed by reaching various benchmarks on the Expanded Disability Status Scale (EDSS) during a median of five years of follow-up.

High NfL blood levels were defined based on the values measured in controls, and multiple cutoff values were assessed. The statistical models used for these calculations were adjusted taking into account other relevant factors, including sex, age, disease duration, and MS treatment.

Overall, high NfL levels were significantly predictive of sustained EDSS worsening (greater disability). Depending on the cutoff used, the risk of disability worsening rose by 40% to 65% in people with high blood NfL levels, compared to those with lower levels.

High NfL levels were also significantly associated with a risk of reaching an EDSS score of 3.0, indicating moderate disability without walking impairment. Similar results were found for reaching an EDSS score of 4.0, indicating significant disability with mild walking impairment.

At some cutoffs, but not others, high NfL was significantly associated with a risk of reaching an EDSS score of 6.o (corresponding to needing an aid to walk 100 meters, about 330 feet). Because statistical significance was not found for all cutoffs assessed, a definitive conclusion cannot be drawn from this data — future studies may help to clarify whether blood NfL levels can predict more severe disability, the researchers noted.

Similarly, high NfL levels were significantly predictive of progression from RRMS to SPMS at some cutoffs, but not at others, making it difficult to draw reliable conclusions and again highlighting a need for further research.

Taken together, the “findings suggest that [blood] NfL measurement can usefully provide additional predictive power in the form of an easily accessible and easy-to-measure biomarker for monitoring of disease activity and potentially treatment response in MS,” the researchers wrote.

Nonetheless, “more research is needed before a blood test could be used routinely in the clinical setting, but our results are encouraging,” Manouchehrinia concluded.