The concentration of plasma neurofilament light chain (pNfL) is associated with clinical and radiologic measures of disease and the effects of treatment in relapsing multiple sclerosis (RMS), according to a study published in the European Journal of Neurology.

This finding supports the use of pNfL as a biomarker of RMS. It is already used as a biomarker of axonal damage in many neurological diseases regardless of cause, including Amyotrophic lateral sclerosis (ALS) and Alzheimer’s disease.

Using data from phase 3 clinical trials of ozanimod in RMS, investigators measured pNfL concentrations before and after 2 doses of ozanimod (0.46 mg or 0.92 mg daily) or interferon β-1a (30 µg weekly) in patients with RMS. The patients were treated as part of the SUNBEAM and RADIANCE trials. They found that the median level of pNfL at baseline was 14.70 pg/mL in the participants of the SUNBEAM trial and 13.35 pg/mL in the participants of the RADIANCE trial.

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Based on MRI outcomes, researchers saw that the gadolinium-enhancing and T2 lesion counts at baselines increased and brain volume decreased with increasing pNfL levels. Moreover, the baseline levels of pNfL were higher in patients who had relapses while on the treatment compared to those who had no relapses.

The median percentage reduction in pNfL concentration was greater in those treated with ozanimod, compared to those treated with interferon β-1a, in both trials. A greater reduction was also associated with fewer gadolinium-enhancing lesions, fewer new or enlarging T2 lesions, less brain volume loss, lower annualized relapse rate, and no evidence of disease activity.

“pNfL was associated with clinical and radiologic measures of disease and treatment effects in RMS, supporting its use as a biomarker,” the authors stated. 

Ozanimod is a sphingosine-1-phosphate (S1P) receptor modulator, which is thought to exert its action by inhibiting the migration of lymphocytes out of peripheral lymphoid tissue into the bloodstream, thereby limiting their ability to reach inflamed tissues and modulating immunity. The treatment is approved in the US under the brand name Zeposia® for the treatment of adult patients with RMS.


Harris S, Comi G, Cree BAC, et al. Plasma neurofilament light chain concentrations as a biomarker of clinical and radiologic outcomes in relapsing multiple sclerosis: post hoc analysis of phase 3 ozanimod trials. Eur J Neurol. Published online July 22, 2021. doi:10.1111/ene.15009