NfL Blood Test May Help Predict MS Activity, Treatment Response

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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Levels of a protein called neurofilament light chain (NfL) in the blood can be used to predict the risk of future disease activity in people with multiple sclerosis (MS), according to a new study.

The results also suggest that changes in NfL levels could be used to deduce the extent to which MS patients are responding to treatments.

“This study brings us a significant step closer to having a blood test that can predict an individual’s risk for upcoming MS disease activity and detect how well their disease-modifying therapy is working,” Robert Fox, MD, a neurologist at Cleveland Clinic, said in a press release.

“Moreover, this represents important progress toward the critical unmet need for biomarkers that give early reflections of treatment response which in turn may both improve clinical care and speed clinical trials testing new therapies,” he added.

Fox is chair of the scientific steering committee at the International Progressive MS Alliance, which helped fund this study alongside Biogen, Celgene, Novartis, Roche, and the Swiss National Science Foundation.

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The study, “Serum neurofilament light chain for individual prognostication of disease activity in people with multiple sclerosis: a retrospective modelling and validation study,” was published in The Lancet Neurology.

NfL is a structural protein inside of nerve cells that leaks out into the surrounding fluid and eventually to the blood when nerve cells are damaged. Measuring NfL in the blood has been explored as a way to indirectly assess disease activity in neurological disorders like MS, which is caused by the immune system erroneously attacking healthy parts of the brain and spinal cord.

A problem with using NfL as a biomarker of disease activity, however, is that levels of this protein vary naturally with age, and also with body mass index (BMI, a ratio of weight to height). These natural variations have made it difficult to establish clear cut-offs for NfL levels, since levels that are “high” in one individual might be within the normal range for someone else.

In the study, an international team of scientists analyzed NfL levels in 10,133 serum samples collected from 5,390 people with no sign of neurological disease. Serum is the non-cellular part of blood.

From these samples, the researchers constructed reference values for NfL levels based on age and BMI. Generally, NfL levels increased with age, and the rate of increase in NfL levels got faster past the age of 50 or so. A higher BMI was generally associated with lower NfL levels.

Based on the data, the team created an online app that other researchers and clinicians can use to calculate NfL references for a given individual.

The team then used these reference values to analyze data for 1,313 people with MS in a Swedish database. Among these patients, about two-thirds were female, nearly all were white, and most had relapsing-remitting disease.

Statistical analyses showed that higher-than-normal NfL levels — as determined based on the calculated references — were “strongly and independently” associated with “clinical and MRI measures of disease worsening or progression,” the researchers said.

Subsequent analyses showed that high NfL levels were predictive of a greater risk of relapsing or experiencing worsening disability. Specifically, people with higher NfL levels were 41% more likely to experience relapses and 11% more likely to experience disability worsening in the following year. They also had a 43% greater likelihood of having evidence of disease activity — which includes relapses, disability worsening, or new or enlarging brain lesions — in that year.

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NfL levels also were associated with treatments: patients treated with monoclonal antibodies (a type of MS therapy generally viewed as high-efficacy) had lower NfL levels than those treated with other medications, and NfL levels were highest in untreated patients.

Analyses of samples taken at different points over time showed that NfL levels dropped more quickly after treatment initiation in patients given higher-efficacy medications. While levels NfL levels remained low in patients receiving these high-efficacy antibodies and oral medications for at least five years, patients receiving low-efficacy medications, such as interferons and glatiramer acetate, had a moderate and transient decrease in NfL levels.

“Our results show that NfL can be used as a biomarker for monitoring of treatment efficacy and prognostication of disease course in individual people with multiple sclerosis,” the researchers concluded.

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