Contributions
Abstract: P635
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - 25 Biomarkers
Background: Improved biomarkers are needed to facilitate clinical decision-making and as surrogate endpoints in clinical trials in multiple sclerosis. We assessed the correlation between levels of neurofilament light chain (NFL) in cerebrospinal fluid (CSF) and serum in patients with clinically isolated syndrome (CIS) and relapsing remitting multiple sclerosis (RRMS) and in healthy controls. We also assessed NFL levels in relation to disease activity during one, two and four years of follow-up and brain volume loss over time.
Methods: In 191 samples from 41 patients with CIS or RRMS and 22 healthy controls, NFL was analysed in CSF using an enzyme-linked immunosorbent assay and in serum using a single-molecule array (Simoa) method. No evidence of disease activity 3 (NEDA-3) status in patients was recorded during four years of follow-up in this prospective longitudinal cohort study and repeated measurements of brain volume, calculated as brain parenchymal fraction (BPF) using SyMRI 8.0 (SyntheticMR), were obtained from 37 patients. All patients were treatment-naïve at baseline.
Results: NFL levels in CSF and serum correlated significantly (Spearman´s rho 0.59, p < 0.001). Receiver operating characteristics (ROC) curves for baseline NFL levels and separation of patients with regard to NEDA-3 status during one, two and four years of follow-up showed a significantly higher area under curve (AUC) for CSF-NFL than for S-NFL at two years (0.85 compared to 0.65, p 0.03), but not at one year (0.81 compared to 0.75, p >0.05) or four years (0.73 compared to 0.69, p >0.05). Linear regression modeling of BPF decrease during the study showed that combining baseline CSF-NFL and mean CSF-NFL during the study resulted in a significant model (adjusted R2 0.28, p 0.002), as did combining baseline number of T2 lesions in brain MRI and number of new T2 lesions in brain MRI during follow-up (adjusted R2 0.20 p 0.008). Among these four variables and baseline BPF, the highest adjusted R2 was achieved by combining baseline CSF-NFL, mean CSF-NFL and baseline number of T2 lesions (adjusted R2 0.33, p 0.001).
Conclusions: NFL levels in CSF and serum correlate, but baseline CSF-NFL may perform better than baseline S-NFL at predicting disease activity during follow-up. Brain volume loss over time seem to be associated with both NFL levels in CSF and T2 lesions in brain MRI and may be best explained in linear regression by a combination of NFL data and MRI data.
Disclosure:
IH, AT, PC, PL and JE have no conflicts of interest to declare.
HZ is one of the founders of Brain Biomarker Solutions in Gothenburg AB, a GU Venture-based platform company at the University of Gothenburg and has served at advisory boards of Roche Diagnostics, Eli Lilly and Pharmasum Therapeutics.
KB has served as a consultant or at advisory boards for Alzheon, BioArctic, Biogen, Eli Lilly, Fujirebio Europe, IBL International, Pfizer and Roche Diagnostics and is also a co-founder of Brain Biomarker Solutions in Gothenburg AB, a GU Venture-based platform company at the University of Gothenburg.
CD has received honoraria for lectures from Biogen Idec, Teva, Sanofi Genzyme and Novartis and served at advisory boards of Roche Diagnostics, Novartis and Biogen Idec
MV has received unrestricted research grants from Biogen and Novartis, honoraria for lectures from Biogen and Genzyme and for advisory boards from Roche and Novartis.
Abstract: P635
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - 25 Biomarkers
Background: Improved biomarkers are needed to facilitate clinical decision-making and as surrogate endpoints in clinical trials in multiple sclerosis. We assessed the correlation between levels of neurofilament light chain (NFL) in cerebrospinal fluid (CSF) and serum in patients with clinically isolated syndrome (CIS) and relapsing remitting multiple sclerosis (RRMS) and in healthy controls. We also assessed NFL levels in relation to disease activity during one, two and four years of follow-up and brain volume loss over time.
Methods: In 191 samples from 41 patients with CIS or RRMS and 22 healthy controls, NFL was analysed in CSF using an enzyme-linked immunosorbent assay and in serum using a single-molecule array (Simoa) method. No evidence of disease activity 3 (NEDA-3) status in patients was recorded during four years of follow-up in this prospective longitudinal cohort study and repeated measurements of brain volume, calculated as brain parenchymal fraction (BPF) using SyMRI 8.0 (SyntheticMR), were obtained from 37 patients. All patients were treatment-naïve at baseline.
Results: NFL levels in CSF and serum correlated significantly (Spearman´s rho 0.59, p < 0.001). Receiver operating characteristics (ROC) curves for baseline NFL levels and separation of patients with regard to NEDA-3 status during one, two and four years of follow-up showed a significantly higher area under curve (AUC) for CSF-NFL than for S-NFL at two years (0.85 compared to 0.65, p 0.03), but not at one year (0.81 compared to 0.75, p >0.05) or four years (0.73 compared to 0.69, p >0.05). Linear regression modeling of BPF decrease during the study showed that combining baseline CSF-NFL and mean CSF-NFL during the study resulted in a significant model (adjusted R2 0.28, p 0.002), as did combining baseline number of T2 lesions in brain MRI and number of new T2 lesions in brain MRI during follow-up (adjusted R2 0.20 p 0.008). Among these four variables and baseline BPF, the highest adjusted R2 was achieved by combining baseline CSF-NFL, mean CSF-NFL and baseline number of T2 lesions (adjusted R2 0.33, p 0.001).
Conclusions: NFL levels in CSF and serum correlate, but baseline CSF-NFL may perform better than baseline S-NFL at predicting disease activity during follow-up. Brain volume loss over time seem to be associated with both NFL levels in CSF and T2 lesions in brain MRI and may be best explained in linear regression by a combination of NFL data and MRI data.
Disclosure:
IH, AT, PC, PL and JE have no conflicts of interest to declare.
HZ is one of the founders of Brain Biomarker Solutions in Gothenburg AB, a GU Venture-based platform company at the University of Gothenburg and has served at advisory boards of Roche Diagnostics, Eli Lilly and Pharmasum Therapeutics.
KB has served as a consultant or at advisory boards for Alzheon, BioArctic, Biogen, Eli Lilly, Fujirebio Europe, IBL International, Pfizer and Roche Diagnostics and is also a co-founder of Brain Biomarker Solutions in Gothenburg AB, a GU Venture-based platform company at the University of Gothenburg.
CD has received honoraria for lectures from Biogen Idec, Teva, Sanofi Genzyme and Novartis and served at advisory boards of Roche Diagnostics, Novartis and Biogen Idec
MV has received unrestricted research grants from Biogen and Novartis, honoraria for lectures from Biogen and Genzyme and for advisory boards from Roche and Novartis.