# The predictive value of serum neurofilament light chain in achieving no evidence of disease activity-3 (NEDA-3) status in treatment-naïve patients with multiple sclerosis

## TL;DR

This study shows that high levels of a protein called sNfL in the blood can predict whether treatment-naive multiple sclerosis patients will achieve a state with no disease activity.

## Contribution

The study demonstrates that sNfL levels are a useful predictor of NEDA-3 status in treatment-naive MS patients.

## Key findings

- High sNfL Z-scores are associated with a lower probability of achieving NEDA-3 in treatment-naive MS patients.
- Gadolinium-enhancing lesions are linked to higher sNfL Z-scores, indicating active inflammation.

## Abstract

Serum neurofilament light chain (sNfL) has emerged as a biomarker reflecting neuroaxonal damage. The role of sNfL in predicting clinical outcome and guiding therapeutic management in multiple sclerosis (MS) is an ongoing research topic. We sought to evaluate sNfL utility for the prediction of achieving No Evidence of Disease Activity-3 (NEDA-3) among MS patients.

We conducted a prospective cohort study including MS patients with a single sNfL measurement at first clinical evaluation. Follow-up was performed every 6 months/clinical relapse and included clinical and MRI evaluation. The main outcome was NEDA-3 achievement during follow-up. sNfL levels were measured, using single-molecule-array (SIMOA) assay. sNfL age- and BMI-normalized Z-scores > 1.5 were defined as high. Linear regression analyses were performed to identify predictors of baseline sNfL Z-score and multivariable Cox proportional hazard regression models were used to evaluate predefined outcomes.

We included 125 patients [age at sNfL measurement:40 ± 12, 30% men, 82% relapsing–remitting and 18% progressive MS]:37 treatment-naïve patients, 88 patients under Disease-Modifying-Treatment (DMT) with 19.1 (Interquartile Range:12.1–24.5) months median follow-up. Prior DMT use [β:-0.93; 95%CI:-1.48– -0.38 p-value:0.001] was negatively associated with baseline sNfL Z-scores. Gadolinium-enhancing lesions were associated with higher sNfL Z-scores [adjusted standardized linear regression coefficient-β:0.68; 95%CI:0.03–1.32; p-value:0.036], contrary to T2-weighted lesion activity (β:0.40; 95%CI:0.17–0.94; p-value:0.232). In treatment-naive patients, high sNfL Z-scores were associated with lower probability of achieving NEDA-3 during follow-up [hazard-ratio:0.35; 95%CI:0.13–0.96; p-value:0.041].

This study demonstrated that gadolinium-enhancing lesions, indicative of active inflammation, are associated with elevated sNfL Z-scores, contrary to T2-weighted lesion-activity and highlights the prognostic value of sNfL in achieving NEDA-3 in treatment-naive patients.