Plasma NfL Levels Predict NEDA-BVL Status as an MS Biomarker

Jarmila Szilasiova, MD, PhD

Data from a recent study published in Multiple Sclerosis Journal suggest that plasma neurofilament light (pNfL) chain levels are a useful biomarker that correlate with no evident disease activity with brain volume loss (NEDA-BVL; NEDA-3 extended by brain volumetry) in relapsing-remitting multiple sclerosis (RRMS).

Researchers performed receiver operating characteristics (ROC) analysis that showed that pNfL predicts NEDA-3 status, with a sensitivity of 92% and specificity of 78% (P <.001) and NEDA-BVL status, with a sensitivity of 80% and specificity of 65% (P <.001).

"Slowing brain atrophy is currently one of the important markers of effective MS treatment... We analyzed the relationship between pNfL and demographic, clinical, and radiological parameters, as well as associations with NEDA-3 and NEDA-BVL in our RRMS cohort. To the best of our knowledge, these variables have not been studied in such a context,” wrote first author Jarmila Szilasiova, MD, PhD, assistant professor, neurology clinic, Pavol Jozef Šafárik University, Košice, and neurologist, Louis Pasteur University Hospital.

Szilasiova and colleagues analyzed data from 95 patients with RRMS enrolled in the cohort study in Louis Pasteur University Hospital in Košice, 59 of which were women (62%). The patients had a mean age of 37.85 years (standard deviation [SD], 9.62), with a median expanded disability status scale (EDSS) score of 3.5 (range, 2.5-4.1).

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Patients’ median disease duration was 8.0 years (interquartile range [IQR], 5-15), and the median pNfL was 8.3 pg/mL (IQR, 6-11.1). First-line disease-modifying therapy (DMT) was used by 63 patients (66.3%) and second line by 32 (33.7%).

Single Molecule Array technology was used to analyze pNfL levels. Brain MRI was performed using a standardized 3D 1-weighted magnetization-prepared rapid gradient-echo sequence and a 3D T2-weighted fluid-attenuated inversion recovery sequence and whole brain (WB) volume and gray matter (GM) volume were measured using the Icobrain program. 

Szilasiova and colleagues found that 45 patients (47.4%) showed NEDA-3 status, while 50 (52.6%) patients showed EDA-3 status. pNfL was significantly higher in the EDA-3 group (11.55 pg/mL [SD, 6.03]) than in the NEDA-3 group (6.99 pg/mL [SD, 1.99]; P <.001). NEDA-BVL status was present in 27 (29.7%) patients and EDA-BVL was present in 68 (70.3%).

Of patients with NEDA-3 status, 32 (68.1%) showed NEDA-BVL status. pNfL was significantly higher in the EDA-BVL group (10.49 pg/mL; SD, 5.72) than in the NEDA-BVL group (6.96 pg/mL [SD, 2.17]; P <.001). The researchers found that after adjusting for age, sex, disease duration, EDSS and pNfL in multivariable logistic regression analysis, pNfL was a significant predictor of NEDA-3 status (B = −0.382; Exp(B) = 0.682; P <.01) and NEDA-BVL status (B = −0.322; Exp(B) = 0.725; P <.01).

ROC curve analysis showed similar results with pNfL and NEDA-3 status (area under the curve (AUC), 0.902 [95% CI, 0.830-0.973]; P <.001), with a sensitivity of 92.3% and a specificity of 78%. Lower pNfL values were more strongly correlated with NEDA-3 status, with a cut-off level of 8.4pg/mL for pNfL.

ROC curve analysis also confirmed pNfL as a predictor of NEDA-BVL status (AUC, 0.757 [95% CI, 0.654-0.860]; P <.001), with a sensitivity of 80% and specificity of 65%. Again, lower pNfL values were more strongly correlated with NEDA-BVL status, with a cut-off level of 7.3pg/mL for pNfL.

“Based on the results of this study, we assume that pNfL has the potential to discriminate those patients having NEDA-3 and NEDA-BVL status. NfL samples taken every 6months may in the future be an alternative to annual brain MRI as a part of a combined assessment of disease activity in individual MS care. pNfL seems to be a supportive marker in those patients who have been apparently stable for a long period or a possible indicator of absent disease activity,” Szilasiova and colleagues concluded.

REFERENCE

Szilasiova J, Mikula P, Rosenberger J, et al. Plasma neurofilament light chain levels are predictors of disease activity in multiple sclerosis as measured by four-domain NEDA status, including brain volume loss. Mult. Slcer. J Published online February 26, 2021. doi: 10.1177/1352458521998039