Serum neurofilament light chain shows modest diagnostic performance for multiple sclerosis disease activitySerum neurofilament light chain shows limited accuracy for MS activity

This meta-analysis evaluated the utility of serum neurofilament light chain (sNfL) as a biomarker for monitoring disease activity in patients with multiple sclerosis (MS). The study included a large aggregate population of 11,213 adults with MS. The primary objective was to assess the diagnostic performance of sNfL specifically regarding inflammatory disease activity.

The analysis focused on identifying the predictive value of sNfL levels and determining optimal cutoffs for clinical utility. Secondary outcomes included the ability of sNfL to predict clinical relapses and the identification of specific thresholds that could inform clinical decision-making. The study aimed to determine if sNfL could serve as a reliable indicator for monitoring MS progression or activity.

Regarding primary outcomes, the diagnostic performance of sNfL for MS disease activity was characterized as modest. The area under the curve (AUC) values ranged from 0.61 to 0.71. These results were noted to be below the prespecified threshold of 0.80 required for high-confidence clinical utility. Consequently, sNfL did not achieve sufficient diagnostic accuracy to serve as a standalone biomarker for inflammatory disease activity in this analysis.

Secondary outcomes focused on predicting clinical relapses and identifying optimal cutoffs. For the prediction of clinical relapse, an optimal cutoff was identified at 10 pg/mL. However, this specific threshold demonstrated limited discriminative performance, with a sensitivity of 0.69, a specificity of 0.65, and an AUC of 0.72. These figures suggest that while sNfL shows some correlation with disease activity, it lacks the precision required for individual patient management.

Safety and tolerability data were not reported in this meta-analysis, as sNfL is a laboratory biomarker rather than a therapeutic intervention. There were no reports of adverse events, serious adverse events, or discontinuations related to the use of sNfL as a diagnostic tool in the included studies.

Methodological limitations significantly impacted the certainty of these findings. The analysis noted substantial methodological heterogeneity across the included studies. Furthermore, there was a high risk of bias in 50% of the studies due to post hoc threshold selection. These factors suggest that the reported values may be influenced by inconsistent study designs and retrospective data selection.

Clinical implications for practice are currently limited. The findings indicate that sNfL did not achieve sufficient diagnostic accuracy for routine clinical use as a standalone biomarker of inflammatory disease activity. Clinicians should not rely on sNfL alone to guide treatment decisions or monitor disease activity at this time.

Several questions remain regarding the role of sNfL in MS management. Future research may need to determine if combining sNfL with other biomarkers can improve diagnostic accuracy. Additionally, more standardized protocols are needed to reduce heterogeneity and bias in future studies evaluating neurofilament levels as a proxy for inflammatory activity.