CSF chitinase 3-like 1 is associated with iron rims in patients with a first demyelinating event

2021 ◽  
pp. 135245852110100
Author(s):  
Manuel Comabella ◽  
Margareta A Clarke ◽  
Sabine Schaedelin ◽  
Mar Tintoré ◽  
Deborah Pareto ◽  
...  
Keyword(s):  
Single Molecule ◽  
Multivariable Analysis ◽  
Enzyme Linked Immunosorbent Assay ◽  
Lesion Volume ◽  
Univariable Analysis ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Multivariable Analyses ◽  
Prognostic Implications ◽  
The Relationship

Background: Chronic active lesions with iron rims have prognostic implications in patients with multiple sclerosis. Objective: To assess the relationship between iron rims and levels of chitinase 3-like 1 (CHI3L1), neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) in patients with a first demyelinating event. Methods: Iron rims were identified using 3T susceptibility-weighted imaging. Serum NfL and GFAP levels were measured by single-molecule array assays. CSF (cerebrospinal fluid) CHI3L1 levels were measured by enzyme-linked immunosorbent assay (ELISA). Results: Sixty-one patients were included in the study. The presence of iron rims was associated with higher T2 lesion volume and higher number of gadolinium-enhancing lesions. In univariable analysis, having ⩾2 iron rims (vs 0) was associated with increased CSF CHI3L1 levels (β = 1.41; 95% confidence interval (CI) = 1.10–1.79; p < 0.01) and serum NfL levels (β = 2.30; 95% CI = 1.47–3.60; p < 0.01). In multivariable analysis, however, only CSF CHI3L1 levels remained significantly associated with the presence of iron rim lesions (β = 1.45; 95% CI = 1.11–1.90; p < 0.01). The presence of ⩾2 iron rims was not associated with increased serum GFAP levels in univariable or multivariable analyses. Conclusion: These findings support an important contribution of activated microglia/macrophages to the pathophysiology of chronic active lesions with iron rims in patients with a first demyelinating event.

scholarly journals Increased Expression of PAD4 in Neutrophils of MPO-ANCA Associated Vasculitis and its Correlation with the Vasculitis Activity

2021 ◽  
Author(s):  
Menglu Pan ◽  
Sen Wang ◽  
Meijuan Zheng ◽  
Weici Zhang ◽  
Zongwen Shuai
Keyword(s):  
Patient Group ◽  
Mean Fluorescence Intensity ◽  
Activity Index ◽  
Multivariable Analysis ◽  
Enzyme Linked Immunosorbent Assay ◽  
Peptidylarginine Deiminase ◽  
Asian Countries ◽  
Univariable Analysis ◽  
Anca Associated Vasculitis ◽  
The Relationship

Myeloperoxidase (MPO)-specific anti-neutrophil cytoplasmic autoantibody (ANCA) associated vasculitis (MPO-AAV) is the most common ANCA associated vasculitis (AAV) in china and other East Asian countries. Its pathogenesis remained elusive. We evaluated the expression of peptidylarginine deiminase (PAD4) in neutrophils from MPO-AAV and explored the relationship between the expression and the vasculitis activity, and also investigated the pathogenic mechanism. 40 patients initially diagnosed with MPO-AAV in the active state and 40 comparable healthy controls (HC) were enrolled in this study. The patient disease activity were evaluated with Birmingham Vasculitis Activity Index version 3 (BVAS-V3). The expression of PAD4 in their neutrophils, which was described as percentage of PAD4+ neutrophils in all neutrophils and mean fluorescence intensity (MFI) of PAD4+ neutrophils, was measured by flow cytometry (FCM). Their serum level of NETs, C5a and MPO-ANCA were detected using enzyme linked immunosorbent assay (ELISA). The percentage of PAD4+ neutrophils, MFI of PAD4+ neutrophils, the levels of serum NETs and C5a were markedly higher in patient group than that in HC group. Meanwhile, in patient group, the percentage of PAD4+ neutrophils, MFI of PAD4+ neutrophils and MPO-ANCA presented significantly correlation with NETs. Although univariable analysis showed the percentage of PAD4+ neutrophils, MFI of PAD4+ neutrophils, NETs, C5a and MPO-ANCA had respective correlation with BVAS, multivariable analysis indicated that only the percentage of PAD4+ neutrophils as well as the level of serious MPO-ANCA owned independent correlations with BVAS.PAD4 might be a new potential target for MPO-AAV treatment in the future.

scholarly journals Brain disconnectome mapping and serum neurofilament light levels in multiple sclerosis

2021 ◽  
Author(s):  
Henning H. Rise ◽  
Synne Brune ◽  
Claudia Chien ◽  
Tone Berge ◽  
Steffan D. Bos ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Single Molecule ◽  
Brain Network ◽  
Axonal Damage ◽  
Base Line ◽  
Lesion Volume ◽  
Neurofilament Light Chain ◽  
Random Factor ◽  
Neurofilament Light ◽  
Multiple Sclerosis Patients

AbstractThe pathophysiological mechanisms for classical plaque characteristics and their predictive value for clinical course and outcome in multiple sclerosis is unclear. Connectivity-based approaches incorporating the distribution and magnitude of the extended brain network aberrations caused by lesions may offer higher sensitivity for axonal damage. Using individual brain disconnectome mapping, we tested the longitudinal associations between putative brain network aberrations and levels of serum neurofilament light chain (sNfL) as a neuroaxonal injury biomarker.Multiple sclerosis patients (n = 328, mean age 42.9 years, 71 % female) were prospectively enrolled at four European multiple sclerosis centres, and reassessed after two years (n = 280). Post-processing of 3 Tesla (3T) MRI data was performed at one centre using a harmonized pipeline, and disconnectome maps were calculated using BCBtoolkit based on individual lesion maps. Global disconnectivity (GD) was defined as the average disconnectome probability in each patient’s white matter. Serum NfL concentrations were measured by single molecule array (Simoa). Robust linear mixed models (rLMM) with GD or T2-lesion volume (T2LV) as dependent variables, patient and centre as a random factor, sNfL, age, sex, timepoint for visit, diagnosis, and treatment as fixed factors were run.Robust LMM revealed significant associations between higher levels of GD and increased sNfL (t = 2.30, β = 0.03, p = 0.02), age (t = 5.01, β = 0.32, p < 5.5 × 10−7), and diagnosis progressive multiple sclerosis (PMS); t = 1.97, β = 1.06, p = 0.05), but not for sex (t = 0.78, p = 0.43), treatments (effective; t = 0.85, p = 0.39, highly-effective; t = 0.86, p = 0.39) or sNfL change between base line and two-year follow up (t = −1.65, p = 0.10). Voxel-wise analyses revealed distributed associations in cerebellar and brainstem regions.In our prospective multi-site multiple sclerosis cohort, rLMMs demonstrated that the extent of global brain disconnectivity is sensitive to a systemic biomarker of axonal damage, sNfL, in patients with multiple sclerosis. These findings provide a neuropathological correlate of advanced disconnectome mapping and provide a platform for further investigations of the functional and clinical relevance in patients with brain disorders.

Serum neurofilament light chain is a biomarker of acute and chronic neuronal damage in early multiple sclerosis

2018 ◽  
Vol 25 (5) ◽  
pp. 678-686 ◽  
Author(s):  
Nelly Siller ◽  
Jens Kuhle ◽  
Muthuraman Muthuraman ◽  
Christian Barro ◽  
Timo Uphaus ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Single Molecule ◽  
Light Chain ◽  
Neuronal Damage ◽  
Axonal Damage ◽  
Lesion Volume ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Magnetic Resonance Imaging Mri ◽  
Brain Parenchymal

Background: Monitoring neuronal injury remains one key challenge in early relapsing-remitting multiple sclerosis (RRMS) patients. Upon axonal damage, neurofilament – a major component of the neuro-axonal cytoskeleton – is released into the cerebrospinal fluid (CSF) and subsequently peripheral blood. Objective: To investigate the relevance of serum neurofilament light chain (sNfL) for acute and chronic axonal damage in early RRMS. Methods: sNfL levels were determined in 74 patients (63 therapy-naive) with recently diagnosed clinically isolated syndrome (CIS) or RRMS using Single Molecule Array technology. Standardized 3 T magnetic resonance imaging (MRI) was performed at baseline and 1–3 consecutive follow-ups (42 patients; range: 6–37 months). Results: Baseline sNfL correlated significantly with T2 lesion volume ( r = 0.555, p < 0.0001). There was no correlation between baseline sNfL and age, Expanded Disability Status Scale (EDSS) score or other calculated MRI measures. However, T2 lesion volume increased ( r = 0.67, p < 0.0001) and brain parenchymal volume decreased more rapidly in patients with higher baseline sNfL ( r = −0.623, p = 0.0004). Gd-enhancing lesions correlated positively with sNfL levels. Initiation of disease-modifying treatment led to a significant decrease in sNfL levels. Conclusion: sNfL indicates acute inflammation as demonstrated by correlation with Gd+ lesions. It is a promising biomarker for neuro-axonal damage in early multiple sclerosis (MS) patients, since higher baseline sNfL levels predicted future brain atrophy within 2 years.

scholarly journals 1118 Examining the Role of Serum and Exosomal Biomarkers in Symptoms of Fatigue and Daytime Sleepiness Following Traumatic Brain Injury

SLEEP ◽  
2020 ◽  
Vol 43 (Supplement_1) ◽  
pp. A426-A426
Author(s):  
J J Leete ◽  
C L Pattinson ◽  
V A Guedes ◽  
C Lai ◽  
C Devoto ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Single Molecule ◽  
Daytime Sleepiness ◽  
Blood Levels ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Ultrasensitive Assay ◽  
Fatigue Severity ◽  
The Relationship

Abstract Introduction Fatigue and daytime sleepiness are two of the most common chronic symptoms reported after traumatic brain injury (TBI). However, there is limited understanding of the pathophysiological mechanisms following TBI that result in these symptoms. Previous research has observed elevations in peripheral blood levels of proteins in TBI patients versus controls, including neurofilament light chain (NFL)—predominantly expressed in long myelinated subcortical axons—and glial fibrillary acidic protein (GFAP)—predominantly expressed in reactive astrocytes responding to central nervous system injuries. This study examines the relationship between serum and exosomal NFL and GFAP, and symptoms of fatigue and daytime sleepiness in TBI patients 1-year after injury. Methods Sixty-seven patients with TBIs ranging from mild to severe were included in this study. Blood samples were collected from all participants 1-year post TBI, with concentrations of GFAP and NFL measured in serum and exosomes using Single Molecule Array technology (Simoa), an ultrasensitive assay. Participants reported fatigue using the Fatigue Severity Scale (FSS), and daytime sleepiness using the Epworth Sleepiness Scale (ESS). Results A linear regression model of fatigue symptoms and exosomal NFL controlling for age revealed that fatigue was negatively associated with exosomal NFL concentrations (β = -.317, p = .041, ηp2 = -.343) and accounted for 20.2% of the change in NFL. Serum NFL concentrations were not associated with fatigue, nor were GFAP serum or exosomes. No significant associations were found between NFL, GFAP, and daytime sleepiness. Conclusion Our findings suggest that exosomal NFL may be related to mechanisms underlying TBI-related fatigue and the potential of NFL as a biomarker of fatigue. To our knowledge, this study is the first to examine the relationship between post-TBI NFL levels and fatigue symptoms. Further investigation into serum and exosome biomarkers of TBI-related fatigue and daytime sleepiness is warranted. Support National Institutes of Health and Center for Neuroscience and Regenerative Medicine

scholarly journals Neurofilament light is a novel biomarker for mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yong-Sheng Zheng ◽  
Chong Sun ◽  
Rong Wang ◽  
Ne Chen ◽  
Su-Shan Luo ◽  
...  
Keyword(s):  
Lactic Acidosis ◽  
Single Molecule ◽  
Acute Attack ◽  
Mitochondrial Encephalomyopathy ◽  
Neurological Dysfunction ◽  
Lesion Volume ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Phase Group ◽  
Remission Phase

AbstractMitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) is a complicated maternally inherited disorder lacking of sensitive and specific biomarkers. The objective of this study was to investigate the serum neurofilament light chain (NfL) as a novel biomarker of neurological dysfunction in MELAS. Patients with different status of MELAS were enrolled in this study. The Mini-Mental State Examination (MMSE) was given to the participants to evaluate cognition status. Multiple functional MRI was performed on the participants. Blood samples were collected and the serum NfL concentrations were determined by the single-molecule array technology (Simoa). This study enrolled 23 patients with MELAS, 15 people in the acute attack phase of MELAS and 10 people in the remission phase, including 2 patients in both acute attack and remission phase. Sixteen healthy controls (HCs) were also enrolled. Serum NfL level increased significantly in patients with MELAS. Serum NfL level in the acute attack group (146.73 [120.91–411.31] pg/ml, median [IQR]) was higher than in the remission group (40.31 [19.54–151.05] pg/ml, median [IQR]) and HCs group (7.70 [6.13–9.78] pg/ml, median [IQR]) (p < 0.05). The level of NfL in the remission phase group was higher than in HCs group (p < 0.05). A negative correlation was found between the serum NfL level and MMSE (p = 0.006, r = -0.650). The NfL concentration correlated positively with stroke-like lesion volume in the brain (r = 0.740, p < 0.001). Serum NfL may serve as a novel biomarker for the neurological dysfunction in MELAS patients.

scholarly journals Plasma neurofilament light chain level predicts outcomes in stroke patients receiving endovascular thrombectomy

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Chih-Hao Chen ◽  
Hai-Jui Chu ◽  
Yi-Ting Hwang ◽  
Yen-Heng Lin ◽  
Chung-Wei Lee ◽  
...  
Keyword(s):  
Scale Score ◽  
Single Molecule ◽  
Light Chain ◽  
Multivariable Analysis ◽  
Hemorrhagic Transformation ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Endovascular Thrombectomy ◽  
Plasma Biomarkers ◽  
Rate Of Increase

Abstract Background Timely endovascular thrombectomy (EVT) significantly improves outcomes in patients with acute ischemic stroke (AIS) with large vessel occlusion type. However, whether certain central nervous system-specific plasma biomarkers correlate with the outcomes is unknown. We evaluated the temporal changes and prognostic roles of the levels of these biomarkers in patients with AIS undergoing EVT. Methods We enrolled 60 patients who received EVT for AIS and 14 controls. The levels of plasma biomarkers, namely neurofilament light chain (NfL), glial fibrillary astrocytic protein (GFAP), tau, and ubiquitin C-terminal hydrolase L1 (UCHL1), were measured with an ultrasensitive single molecule array before, immediately after, and 24 h after EVT (T1, T2, and T3, respectively). The outcomes of interest were death or disability at 90 days (defined as a modified Rankin Scale score of 3–6) and types of hemorrhagic transformation (hemorrhagic infarction or parenchymal hemorrhage). Results Of the 180 blood samples from the 60 patients who received EVT, the plasma NfL, GFAP, and UCHL1 levels at T1 were significantly higher than those of the controls, and the levels of all four biomarkers were significantly higher at T3. Patients with parenchymal hemorrhage had a significantly higher rate of increase in GFAP (Pinteraction = 0.005) and UCHL1 (Pinteraction = 0.007) levels compared with those without parenchymal hemorrhage. In a multivariable analysis with adjustment for age, sex, National Institute of Health Stroke Scale score, history of atrial fibrillation, and recanalization status, higher NfL levels at T1 (odds ratio [OR] 2.05; 95% confidence interval [CI], 1.03–4.08), T2 (OR, 2.08; 95% CI, 1.05–4.01), and T3 (OR, 3.94; 95% CI, 1.44–10.79) were independent predictors of death or disability at 90 days. Conclusion Among patients with AIS who received EVT, those with hemorrhagic transformation exhibited significant increase in plasma GFAP and UCHL1 levels over time. Higher plasma NfL were predictive of unfavorable functional outcomes.

scholarly journals Serum Neurofilament Light Chain Levels and Myelin Oligodendrocyte Glycoprotein Antibodies in Pediatric Acquired Demyelinating Syndromes

2021 ◽  
Vol 12 ◽  
Author(s):  
Marta Simone ◽  
Claudia Palazzo ◽  
Mariangela Mastrapasqua ◽  
Luca Bollo ◽  
Francesco Pompamea ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Single Molecule ◽  
Light Chain ◽  
Myelin Oligodendrocyte Glycoprotein ◽  
Oligoclonal Bands ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Significant Difference ◽  
The Relationship

Introduction: The relationship between serum neurofilament light chain (sNfL) and myelin oligodendrocyte glycoprotein antibody (MOG-Ab) status has not been yet investigated in children with the acquired demyelinating syndrome (ADS).Objective and Methods: The sNfL levels and MOG-Abs were measured by ultrasensitive single-molecule array and cell-based assay in a cohort of 37 children with ADS and negativity for serum anti-aquaporin 4 (AQP4) antibodies. The sNfL levels were compared in MOG-Ab+/MOG-Ab– and in two subgroups MOG-Ab+ with/without encephalopathy.Results: About 40% ADS resulted in MOG-Ab+. MOG-Ab+ were younger at sampling (median = 9.8; range = 2.17–17.5 vs. 14.7/9–17; p = 0.002) with lower frequency of cerebrospinal fluid oligoclonal bands positivity (27% vs. 70%; p = 0.013) compared to MOG-Ab–. About 53% of MOG-Ab+ presented encephalopathy at onset, 1/22 of MOG-Ab– (p = 0.0006). Higher sNfL levels (p = 0.0001) were found in MOG-Ab+ (median/range = 11.11/6.8–1,129) and MOG-Ab– (median/range = 11.6/4.3–788) compared to age-matched controls (median/range = 2.98/1–4.53), without significant difference. MOG-Ab+ with encephalopathy resulted significantly younger at sampling (median/range: 4.5/2.17–11.17 vs. 14.16/9.8–17.5; p = 0.004), had higher sNfL levels (median/range:75.24/9.1–1,129 vs. 10.22/6.83–50.53; p = 0.04), and showed a trend for higher MOG-Ab titer (0.28/0.04–0.69 vs. 0.05/0.04–0.28; p = 0.1) in comparison to those without encephalopathy.Discussion: We confirmed high sNfL levels in pediatric ADS independently from the MOG-Ab status. Encephalopathy at onset is associated more frequently with MOG Ab+ children with higher sNfL levels and MOG titer. These findings suggest a role of acute demyelination in association with axonal damage in the pathogenesis of encephalopathy in pediatric ADS.

scholarly journals Plasma NfL levels and longitudinal change rates in C9orf72 and GRN-associated diseases: from tailored references to clinical applications

2021 ◽  
pp. jnnp-2021-326914
Author(s):  
Dario Saracino ◽  
Karim Dorgham ◽  
Agnès Camuzat ◽  
Daisy Rinaldi ◽  
Armelle Rametti-Lacroux ◽  
...  
Keyword(s):  
Single Molecule ◽  
Light Chain ◽  
Rate Of Change ◽  
Longitudinal Change ◽  
Youden Index ◽  
Clinical Genetic ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Link Type ◽  
Therapeutic Trials

ObjectiveNeurofilament light chain (NfL) is a promising biomarker in genetic frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). We evaluated plasma neurofilament light chain (pNfL) levels in controls, and their longitudinal trajectories in C9orf72 and GRN cohorts from presymptomatic to clinical stages.MethodsWe analysed pNfL using Single Molecule Array (SiMoA) in 668 samples (352 baseline and 316 follow-up) of C9orf72 and GRN patients, presymptomatic carriers (PS) and controls aged between 21 and 83. They were longitudinally evaluated over a period of >2 years, during which four PS became prodromal/symptomatic. Associations between pNfL and clinical–genetic variables, and longitudinal NfL changes, were investigated using generalised and linear mixed-effects models. Optimal cut-offs were determined using the Youden Index.ResultspNfL levels increased with age in controls, from ~5 to~18 pg/mL (p<0.0001), progressing over time (mean annualised rate of change (ARC): +3.9%/year, p<0.0001). Patients displayed higher levels and greater longitudinal progression (ARC: +26.7%, p<0.0001), with gene-specific trajectories. GRN patients had higher levels than C9orf72 (86.21 vs 39.49 pg/mL, p=0.014), and greater progression rates (ARC:+29.3% vs +24.7%; p=0.016). In C9orf72 patients, levels were associated with the phenotype (ALS: 71.76 pg/mL, FTD: 37.16, psychiatric: 15.3; p=0.003) and remarkably lower in slowly progressive patients (24.11, ARC: +2.5%; p=0.05). Mean ARC was +3.2% in PS and +7.3% in prodromal carriers. We proposed gene-specific cut-offs differentiating patients from controls by decades.ConclusionsThis study highlights the importance of gene-specific and age-specific references for clinical and therapeutic trials in genetic FTD/ALS. It supports the usefulness of repeating pNfL measurements and considering ARC as a prognostic marker of disease progression.Trial registration numbersNCT02590276 and NCT04014673.

scholarly journals Blood neurofilament light concentration at admittance: a potential prognostic marker in COVID-19

2021 ◽  
Author(s):  
Anne Hege Aamodt ◽  
Einar August Høgestøl ◽  
Trine Haug Popperud ◽  
Jan Cato Holter ◽  
Anne Ma Dyrhol-Riise ◽  
...  
Keyword(s):  
Nervous System ◽  
Single Molecule ◽  
Linear Models ◽  
Clinical Signs ◽  
Repeated Measurements ◽  
Cns Injury ◽  
Serum Concentrations ◽  
Blood Biomarkers ◽  
Neurofilament Light Chain ◽  
Neurofilament Light

Abstract Objective To test the hypotheses that blood biomarkers for nervous system injury, serum concentrations of neurofilament light chain protein (NfL) and glial fibrillary acidic protein (GFAp) can serve as biomarkers for disease severity in COVID-19 patients. Methods Forty-seven inpatients with confirmed COVID-19 had blood samples drawn on admission for assessing serum biomarkers of CNS injury by Single molecule array (Simoa), NfL and GFAp. Concentrations of NfL and GFAp were analyzed in relation to symptoms, clinical signs, inflammatory biomarkers and clinical outcomes. We used multivariate linear models to test for differences in biomarker concentrations in the subgroups, accounting for confounding effects. Results In total, 21% (n = 10) of the patients were admitted to an intensive care unit, and the overall mortality rate was 13% (n = 6). Non-survivors had higher serum concentrations of NfL (p < 0.001) upon admission than patients who were discharged alive both in adjusted analyses (p = 2.6 × 10–7) and unadjusted analyses (p = 0.001). The concentrations of NfL in non-survivors increased over repeated measurements; whereas, the concentrations in survivors were stable. The GFAp concentration was also significantly higher in non-survivors than survivors (p = 0.02). Conclusion Increased concentrations of NfL and GFAp in COVID-19 patients on admission may indicate increased mortality risk. Measurement of blood biomarkers for nervous system injury can be useful to detect and monitor CNS injury in COVID-19.

Sustained reduction of serum neurofilament light chain over 7 years by alemtuzumab in early relapsing–remitting MS

2021 ◽  
pp. 135245852110323
Author(s):  
Jens Kuhle ◽  
Nadia Daizadeh ◽  
Pascal Benkert ◽  
Aleksandra Maceski ◽  
Christian Barro ◽  
...  
Keyword(s):  
Single Molecule ◽  
Light Chain ◽  
Interferon Beta ◽  
Efficacy And Safety ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Highly Active ◽  
Sustained Reduction ◽  
Relapsing Remitting ◽  
Healthy Control

Background: Alemtuzumab efficacy and safety was demonstrated in CARE-MS I and extension studies (CAMMS03409; TOPAZ). Objective: Evaluate serum neurofilament light chain (sNfL) in CARE-MS I patients and highly active disease (HAD) subgroup, over 7 and 2 years for alemtuzumab and subcutaneous interferon beta-1a (SC IFNB-1a), respectively. Methods: Patients received SC IFNB-1a 44 µg 3×/week or alemtuzumab 12 mg/day at baseline and month 12, with further as-needed 3-day courses. sNfL was measured using single-molecule array (Simoa™). HAD definition was ⩾2 relapses in year before randomization and ⩾1 baseline gadolinium-enhancing lesion. Results: Baseline median sNfL levels were similar in alemtuzumab ( n = 354) and SC IFNB-1a–treated ( n = 159) patients (31.7 vs 31.4 pg/mL), but decreased with alemtuzumab versus SC IFNB-1a until year 2 (Y2; 13.2 vs 18.7 pg/mL; p < 0.0001); 12.7 pg/mL for alemtuzumab at Y7. Alemtuzumab-treated patients had sNfL at/below healthy control median at Y2 (72% vs 47%; p < 0.0001); 73% for alemtuzumab at Y7. HAD patients ( n = 102) had higher baseline sNfL (49.4 pg/mL) versus overall population; alemtuzumab HAD patients attained similar levels (Y2, 12.8 pg/mL; Y7, 12.7 pg/mL; 75% were at/below control median at Y7). Conclusion: Alemtuzumab was superior to SC IFNB-1a in reducing sNfL, with levels in alemtuzumab patients remaining stable through Y7. ClinicalTrials.gov identifier: NCT00530348, NCT00930553, NCT02255656

Sign in / Sign up

Export Citation Format

Share Document