Neurofilament Light Chain Levels in Blood of Value as Biomarker of MS Activity and Treatment Response, Study Finds

Blood levels of a nerve cell-derived component known as neurofilament light chain (NfL) could be used as a biomarker of disease severity and treatment response in patients with relapsing-remitting multiple sclerosis (RRMS), a new study shows.

The research article, “Blood neurofilament light chain as a biomarker of MS disease activity and treatment response,” was published in the journal Neurology.

Currently, brain cell damage or loss in multiple sclerosis (MS) patients is assessed using magnetic resonance imaging (MRI) — an imaging technique that generates images of organs. However, brain MRI assessments are costly, difficult to standardize, and require complex analysis after the exam.

A disease biomarker that is more cost-effective, and easier to use and interpret could have a huge impact on the long-term monitoring of MS in both clinical practice and clinical trials.

NfL is exclusively present in nerve cells; therefore, NfL presence in blood or cerebral spinal fluid is a sign of neuron degeneration. Studies have shown that high levels of NfL in blood and cerebrospinal fluid are associated with an increased number of MS relapses, disability worsening, brain volume loss, and disease activity in MS.

A highly sensitive and reliable immunoassay — called SIMOA — has been developed to measure NfL levels in blood samples, which are easier and safer to obtain from patients than cerebrospinal fluid samples.

To further assess the prognostic value of NfL in MS, researchers with Novartis and collaborating universities used blood samples from RRMS patients taking part in two large, Phase 3 controlled clinical trials testing the MS therapy Gilenya (fingolimod, marketed by Novartis).

Blood samples from 269 RRMS patients from the FREEDOMS (NCT00289978) trial, 320 patients from the TRANSFORMS (NCT00340834) trial, and 35 healthy controls were assessed for NfL levels, and compared with clinical and MRI-related outcomes.

At baseline (measures taken prior to the start of each trial), the patients had about twice the levels of NfL in their blood compared with healthy controls — 30.5 pg/mL among those FREEDOMS, and 27.0 pg/mL in TRANSFORMS, versus 16.9 pg/mL in controls.

NfL levels at baseline were also found to correlate with MRI markers of disease activity, like brain lesion load and tissue destruction (brain volume loss). RRMS patients with MRI lesions had higher blood NfL levels than patients without lesions.

In both FREEDOM (a two-year study) and TRANSFORM (one year), Gilenya treatment was associated with lower NfL blood levels compared to treatment with placebo or IFN-β-1a. This effect was seen in measures first taken at six months of treatment until the end of each trial, suggesting that blood NfL levels are useful in assessing treatment response.

“We have shown that blood neurofilament light chain levels are closely related to clinical and MRI measures in patients with RRMS, which capture features of acute disease activity, worsening of disability, and tissue loss,” the researchers wrote.

“In contrast to imaging markers, it is feasible to measure blood NfL serially, with minimal burden to the patient. NfL levels in blood appear suitable to monitor disease activity and drug response in real time,” they added.

Interestingly, researchers noticed that categorizing RRMS patients according to their blood NfL levels at baseline — high versus low — was predictive of a greater risk of new or enlarging lesions, relapses, and accelerated brain volume loss over two years.

These findings suggest that blood NfL levels at baseline could be indicators (have a prognostic value) of future disease activity and progression.

“Together, these results suggest that NfL in blood is likely to reflect an integral measure of recent and ongoing neuronal damage (over weeks, and possibly months),” the team wrote.

Based on the results, researchers suggested creating a database to catalog NfL levels in MS patients, with the purpose of strengthening neurofilament light chain’s prognostic utility. Using this database to collect information on factors including age, length of disease, and comorbidities could inform treatment decisions at the individual level.