Increasing serum neurofilament light chain (sNfL) levels show promising results as a new biomarker for multiple sclerosis (MS) relapses, according to results of a new study published in Multiple Sclerosis and Related Disorders.

The authors demonstrated that a 2-fold increase in sNfL compared to a 1-month-old measure was associated with a 2.3-fold higher risk of relapse. Furthermore, when comparing current sNfL levels to data from 1 year prior, patients with a 2-fold increase had an additional increased risk of relapse of 1.46 times.

While higher levels of sNfL have long been used as a biomarker for long-term negative outcomes, a team of researchers led by Simon Thebault aimed to determine the clinical significance of longitudinal serum increases.

Continue Reading

This prospective study included patients with MS with evidence of recent disease activity who enrolled in a 1-year phase 2 clinical trial that studied the safety and efficacy of autologous mesenchymal stem cells and underwent clinical assessments, magnetic resonance imaging (MRI), and sNfL and serum glial fibrillary acidic protein (sGFAP) quantification every 3 months or less.

Read more about MS diagnosis

All 58 participants were classified according to sNfL levels on the first visit into a “low” group (<10 pg/mL) that included 17 patients, an “intermediate” group (10-20 pg/mL) with 23 patients, or a “high” group (>20 pg/mL) with 18 patients. Relapse was defined as any perceived change in symptoms or signs that increased the Expanded Disability Status Score by at least 0.5-1.0 points for 48 hours or more.

Nineteen patients experienced a combined total of 34 relapses, and among these, 4 were from the low group, 6 were from the intermediate group, and 23 were from the high group, yielding an absolute risk of relapse difference in the high group vs low group of 104.3% and a relative risk of 444%.

Like sNfL, sGFAP has been proposed as a disease-progression biomarker, although its use in medical practice is not completely understood. In this study, sGFAP was only associated with future MRI activity, and no link was evident to relapses or other clinical outcomes. “Additional endpoints may be more relevant to sGFAP prediction including MRI brain volume loss and Progression Independent of Relapse Activity,” the authors wrote.

“In some jurisdictions where sNfL is already approved and used for monitoring MS subclinical disease activity, our data may assist clinicians in assessing the possible need for treatment optimization in a given patient,” the authors concluded.


Thebault S, Reaume M, Marrie RA, et al. High or increasing serum NfL is predictive of impending multiple sclerosis relapses. Mult Scler Relat Disord. Published online January 19, 2022. doi:10.1016/j.msard.2022.103535