Temporal profile of serum neurofilament light in multiple sclerosis: Implications for patient monitoring

Calabresi, Peter A.; Arnold, Douglas L.; Sangurdekar, Dipen; Singh, Carol M.; Altincatal, Arman; Moor, Carl de; Engle, Bob; Goyal, Jaya; Deykin, Aaron; Szak, Suzanne; Kieseier, Bernd C.; Rudick, Richard A.; Plavina, Tatiana

doi:10.1177/1352458520972573

Cited by 26 publications

(59 citation statements)

References 34 publications

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“…Considering the temporal increase of sNfL levels following axonal injury over 3 to 6 months, 35 studies are also required to investigate the optimal frequency of sNfL assessment. 12,18,19 In this respect, more frequent sNfL assessment may further improve identification of patients at higher risk of future disease activity.…”

Section: Discussionmentioning

confidence: 99%

“…An increasing number of studies has established sNfL as marker of disease activity, drug response, and prediction of the disease course, both on clinical and MRI grounds. 9 –19 However, the practical value of sNfL as a monitoring tool for clinical practice has been less studied. 13 –20…”

Section: Introductionmentioning

confidence: 99%

“…9 –19 However, the practical value of sNfL as a monitoring tool for clinical practice has been less studied. 13 –20…”

Section: Introductionmentioning

confidence: 99%

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Measurement of neurofilaments improves stratification of future disease activity in early multiple sclerosis

et al. 2021

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Background: The added value of neurofilament light chain levels in serum (sNfL) to the concept of no evidence of disease activity-3 (NEDA-3) has not yet been investigated in detail. Objective: To assess whether combination of sNfL with NEDA-3 status improves identification of patients at higher risk of disease activity during the following year. Methods: We analyzed 369 blood samples from 155 early relapsing-remitting MS patients on interferon beta-1a. We compared disease activity, including the rate of brain volume loss in subgroups defined by NEDA-3 status and high or low sNfL (> 90th or < 90th percentile). Results: In patients with disease activity (EDA-3), those with higher sNFL had higher odds of EDA-3 in the following year than those with low sNFL (86.5% vs 57.9%; OR = 4.25, 95% CI: [2.02, 8.95]; p = 0.0001) and greater whole brain volume loss during the following year (β = −0.36%; 95% CI = [−0.60, −0.13]; p = 0.002). Accordingly, NEDA-3 patients with high sNfL showed numerically higher disease activity (EDA-3) in the following year compared with those with low sNfL (57.1% vs 31.1%). Conclusion: sNfL improves the ability to identify patients at higher risk of future disease activity, beyond their NEDA-3 status. Measurement of sNfL may assist clinicians in decision-making by providing more sensitive prognostic information.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Measurement of neurofilaments improves stratification of future disease activity in early multiple sclerosis

et al. 2021

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“…For multiple sclerosis (MS), it has been reported that baseline serum NfL (sNfL) is a predictor of long-term brain atrophy, development of new T2 lesions, T2 lesion volume, gadolinium (Gd+) lesions, and increased likelihood of progression from radiologically isolated syndromes or clinically isolated syndromes to clinically definite MS (10, 11). In addition, sNfL levels are higher and more variable in patients with evidence of active MS and decrease with a DMT (11). Multiple reports have shown that sNfL levels are responsive to treatment with MS DMTs (12-15).…”

Section: Introductionmentioning

confidence: 99%

Development of a Highly Sensitive Serum Neurofilament Light Chain Assay on an Automated Immunoassay Platform

Uzgiris

Calabresi

Stevenson

et al. 2022

Preprint

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Background: Neurofilament light chain (NfL) is an axonal cytoskeletal protein that is released into the extracellular space following neuronal or axonal injury associated with neurological conditions such as multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), and other diseases. NfL is detectable in cerebrospinal fluid (CSF) and blood. Numerous studies in MS have demonstrated that NfL correlates with disease activity, predicts disease progression, and is reduced by treatment with MS disease-modifying drugs, making NfL an attractive candidate to supplement existing clinical and imaging measures in MS. However, for NfL to achieve its potential as a clinically useful biomarker for clinical decision-making or drug development, a standardized, practical, widely accessible assay is needed. Our objective was to validate the analytical performance of the novel serum neurofilament light (sNfl) assay on the ADVIA Centaur(r) XP immunoassay system. Methods: The research assay was evaluated on the ADVIA Centaur XP immunoassay system from Siemens Healthineers. The lower limit of quantitation (LLoQ), intra-assay variation, assay range, cross-reactivity with neurofilament medium and heavy chains, and effect of interfering substances were determined. NfL assay values in serum and CSF were compared with radiological and clinical disease activity measures in patients with MS and ALS, respectively. This assay was further optimized to utilize serum, plasma, and CSF sample types and transferred to Siemens' CLIA laboratory, where it was analytically validated as a laboratory-developed test. Results: In this study, a LLoQ of 1.85 pg/mL, intra-assay variation of <6%, and an assay range of up to 646 pg/mL were demonstrated. A cross-reactivity of <0.7% with neurofilament medium and heavy chains was observed, and the assay was not significantly affected by various interfering substances encountered in clinical specimens. Serum and CSF NfL assay values were associated with radiological and clinical disease activity measures in patients with MS and ALS, respectively. Conclusion: The analytical performance of the NfL assay fulfilled all acceptance criteria; therefore, we believe the assay is acceptable for use in both research and clinical practice settings to determine elevated sNfL levels in patients.

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“…Recently, measurement of a structural axonal protein, neurofilament, in serum or plasma has shown promise as a marker of neuroaxonal injury and a measure of treatment response. 6 , 7 …”

Section: Introductionmentioning

confidence: 99%

Measuring treatment response to advance precision medicine for multiple sclerosis

Calabresi

Kappos

Giovannoni

et al. 2021

Ann Clin Transl Neurol

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Objective: To assess the independent contributions of clinical measures (relapses, Expanded Disability Status Scale [EDSS] scores, and neuroperformance measures) and nonclinical measures (new brain magnetic resonance imaging [MRI] activity and serum neurofilament light chain [sNfL] levels) for distinguishing natalizumab-treated from placebo-treated patients. Methods: We conducted post hoc analyses using data from the AFFIRM trial of natalizumab for multiple sclerosis. We used multivariable regression analyses with predictors (EDSS progression, no relapse, new or enlarging MRI activity, brain atrophy, sNfL levels, and neuroperformance worsening) to identify measures that independently discriminated between treatment groups. Results: The multivariable model that best distinguished natalizumab from placebo was no new or enlarging T2 or gadolinium-enhancing activity on MRI (odds ratio; 95% confidence interval: 7.2; 4.7-10.9), year 2 sNfL levels <97.5th percentile (4.1; 2.6-6.2), and no relapses in years 0-2 (2.1; 1.5-3.0). The next best-fitting model was a twocomponent model that included no MRI activity and sNfL levels <97.5th percentile at year 2. There was little difference between the three-and twocomponent models. Interpretation: Nonclinical measures (new MRI activity and sNfL levels) discriminate between treatment and placebo groups similarly to or better than clinical outcomes composites and have implications for patient monitoring.

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Temporal profile of serum neurofilament light in multiple sclerosis: Implications for patient monitoring

Cited by 26 publications

References 34 publications

Measurement of neurofilaments improves stratification of future disease activity in early multiple sclerosis

Measurement of neurofilaments improves stratification of future disease activity in early multiple sclerosis

Development of a Highly Sensitive Serum Neurofilament Light Chain Assay on an Automated Immunoassay Platform

Measuring treatment response to advance precision medicine for multiple sclerosis

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