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Background <p>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.</p> Methods <p>We conducted a prospective cohort study including MS patients with a single sNfL measurement at first clinical evaluation. Follow-up was performed every 6&#xa0;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 &gt; 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.</p> Results <p>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 <i>p</i>-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; <i>p</i>-value:0.036], contrary to T2-weighted lesion activity (β:0.40; 95%CI:0.17–0.94; <i>p</i>-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; <i>p</i>-value:0.041].</p> Conclusions <p>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.</p>

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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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年3月9日

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  • Evangelia Makrina Dimitriadou,
  • Dimitrios Tzanetakos,
  • Aikaterini Theodorou,
  • Alexandra Akrivaki,
  • Dimitrios Papadopoulos,
  • Vasileios Mastorodemos,
  • Aleksandra Maleska,
  • Stefania Alexia Sotirli,
  • Nikolaos Fakas,
  • Christos Stergiou,
  • Dimitrios Kitsos,
  • Vasileios Giannopapas,
  • Christos Moschovos,
  • Sotirios Giannopoulos,
  • Jens Kuhle,
  • Georgios Tsivgoulis,
  • John S. Tzartos

摘要

Background

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.

Methods

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.

Results

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].

Conclusions

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.