Contributions
Abstract: P849
Type: Poster Sessions
Abstract Category: Pathology and pathogenesis of MS - Biomarkers
Background: Serum neurofilament light chain (sNfL) quantifies neuroaxonal injury in blood samples and has a promising potential to be implemented in routine clinical practice.
Objectives: The project primarily focused on evaluating whether sNfL in patients after first demyelinating event suggestive of multiple sclerosis (MS) may predict future disease activity.
Methods: 157 patients from the original SET cohort (Study of Early Interferon b1-a Treatment in patients after first demyelinating event suggestive of MS) and 40 age matched healthy controls participated in this project. Clinical and MRI data were collected regularly over the course of four years. EDSS (Expanded Disability Status Scale) was performed at least every six months. Annual MRI data included brain parenchymal fraction (BPF), corpus callosum volume (CCV), T2 lesion volume (T2LV) and gadolinium enhancing lesion number (GAD lesions). We analyzed the levels of sNfL collected at screening, i.e., before intravenous corticosteroids, and in the first month after initiation of disease-modifying drugs (M1). To estimate the predictive potential of early sNfL levels, we divided the patients into two groups based on NEDA 3 (no evidence of disease activity) at four years of follow up. The sNfL levels were measured by single molecule array (Simoa) assay.
Results: Patients exhibited significantly higher sNfL levels than healthy controls (p< 0.001). The correlation between both sNfL time points was very strong (rho=0.78; p< 0.05). The sNfL level highly correlated with MRI parameters at baseline (T2LV, rho=0.50; GAD lesions, rho=0.38; p< 0.01), except for BPF, and slightly correlated with EDSS at M48 (rho=0.27; p< 0.01). Interestingly, patients with sNfL levels in the highest tertile had significantly lower BPF at M48 compared with the rest of the patients (p< 0.01). Similarly, patients with sNfL levels within the highest tertile had significantly higher volume of T2 lesions at M48 (p< 0.001). NEDA 3 (n=18) versus no NEDA 3 (n=127) patients over the monitored four years showed lower levels of early sNfL (median=13.58, interquartile range 7.89-15.63 pg/ml versus median=18.64, interquartile range 11.85-37.13 pg/ml; p< 0.001).
Conclusions: Increased early sNfL levels in patients after first demyelinating event suggestive of MS are associated with higher clinical and radiological disease activity. Congruently, lower sNfL level is associated with sustained NEDA 3 status over four years follow up.
Disclosure: Barbora Benova received compensation for traveling and conference fees from Novartis, Sanofi Genzyme and Biogen.
Christian Barro received conference travel grant from Teva and Novartis.
Michaela Andelova received compensation for traveling and conference fees from Novartis, Merck and Biogen.
Zuzanna Michalak reports no disclosures.
Karolina Kucerova reports no disclosures.
Tereza Hrnciarova reports no disclosures.
Tomas Uher received financial support for conference travel and honoraria from Biogen Idec, Novartis, Genzyme, Roche and Merck Serono.
Dr. Vaneckova received financial support for research activities from Biogen Idec and received financial support for conference travel and honoraria from Biogen Idec, Novartis, Genzyme and Merck Serono.
Eva Havrdova received speaker honoraria and consultant fees from Biogen Idec, Merck Serono, Novartis, Genzyme and Teva, as well as support for research activities from Biogen Idec and Merck Serono.
Dana Horakova received compensation for travel, speaker honoraria, and consultant fees from Biogen Idec, Novartis, Merck, Bayer, Sanofi Genzyme, and Teva, as well as support for research activities from Biogen Idec.
Jiri Motyl received compensation for travelling and conference fees from Novartis and Merck.
Lucie Kadrnozkova received compensation for travelling and conference fees from Novartis and Merck.
Michaela Tyblova received financial support for conference travel from Biogen Idec, Novartis, Genzyme, Roche and Merck Serono.
Jens Kuhle received speaker fees, research support, travel support, and/or served on advisory boards by ECTRIMS, Swiss MS Society, Swiss National Research Foundation, (320030_160221), University of Basel, Bayer, Biogen, Genzyme, Merck, Novartis, Protagen AG, Roche, Teva.
The project was supported by the Charles University Grant Agency (GAUK) 230217, Czech Ministry of Education project PRVOUK-P26/LF1/4, Czech Ministry of Health project RVO-VFN64165 and grant NV18-04-00168.
Research grant was provided by Biogen.
Abstract: P849
Type: Poster Sessions
Abstract Category: Pathology and pathogenesis of MS - Biomarkers
Background: Serum neurofilament light chain (sNfL) quantifies neuroaxonal injury in blood samples and has a promising potential to be implemented in routine clinical practice.
Objectives: The project primarily focused on evaluating whether sNfL in patients after first demyelinating event suggestive of multiple sclerosis (MS) may predict future disease activity.
Methods: 157 patients from the original SET cohort (Study of Early Interferon b1-a Treatment in patients after first demyelinating event suggestive of MS) and 40 age matched healthy controls participated in this project. Clinical and MRI data were collected regularly over the course of four years. EDSS (Expanded Disability Status Scale) was performed at least every six months. Annual MRI data included brain parenchymal fraction (BPF), corpus callosum volume (CCV), T2 lesion volume (T2LV) and gadolinium enhancing lesion number (GAD lesions). We analyzed the levels of sNfL collected at screening, i.e., before intravenous corticosteroids, and in the first month after initiation of disease-modifying drugs (M1). To estimate the predictive potential of early sNfL levels, we divided the patients into two groups based on NEDA 3 (no evidence of disease activity) at four years of follow up. The sNfL levels were measured by single molecule array (Simoa) assay.
Results: Patients exhibited significantly higher sNfL levels than healthy controls (p< 0.001). The correlation between both sNfL time points was very strong (rho=0.78; p< 0.05). The sNfL level highly correlated with MRI parameters at baseline (T2LV, rho=0.50; GAD lesions, rho=0.38; p< 0.01), except for BPF, and slightly correlated with EDSS at M48 (rho=0.27; p< 0.01). Interestingly, patients with sNfL levels in the highest tertile had significantly lower BPF at M48 compared with the rest of the patients (p< 0.01). Similarly, patients with sNfL levels within the highest tertile had significantly higher volume of T2 lesions at M48 (p< 0.001). NEDA 3 (n=18) versus no NEDA 3 (n=127) patients over the monitored four years showed lower levels of early sNfL (median=13.58, interquartile range 7.89-15.63 pg/ml versus median=18.64, interquartile range 11.85-37.13 pg/ml; p< 0.001).
Conclusions: Increased early sNfL levels in patients after first demyelinating event suggestive of MS are associated with higher clinical and radiological disease activity. Congruently, lower sNfL level is associated with sustained NEDA 3 status over four years follow up.
Disclosure: Barbora Benova received compensation for traveling and conference fees from Novartis, Sanofi Genzyme and Biogen.
Christian Barro received conference travel grant from Teva and Novartis.
Michaela Andelova received compensation for traveling and conference fees from Novartis, Merck and Biogen.
Zuzanna Michalak reports no disclosures.
Karolina Kucerova reports no disclosures.
Tereza Hrnciarova reports no disclosures.
Tomas Uher received financial support for conference travel and honoraria from Biogen Idec, Novartis, Genzyme, Roche and Merck Serono.
Dr. Vaneckova received financial support for research activities from Biogen Idec and received financial support for conference travel and honoraria from Biogen Idec, Novartis, Genzyme and Merck Serono.
Eva Havrdova received speaker honoraria and consultant fees from Biogen Idec, Merck Serono, Novartis, Genzyme and Teva, as well as support for research activities from Biogen Idec and Merck Serono.
Dana Horakova received compensation for travel, speaker honoraria, and consultant fees from Biogen Idec, Novartis, Merck, Bayer, Sanofi Genzyme, and Teva, as well as support for research activities from Biogen Idec.
Jiri Motyl received compensation for travelling and conference fees from Novartis and Merck.
Lucie Kadrnozkova received compensation for travelling and conference fees from Novartis and Merck.
Michaela Tyblova received financial support for conference travel from Biogen Idec, Novartis, Genzyme, Roche and Merck Serono.
Jens Kuhle received speaker fees, research support, travel support, and/or served on advisory boards by ECTRIMS, Swiss MS Society, Swiss National Research Foundation, (320030_160221), University of Basel, Bayer, Biogen, Genzyme, Merck, Novartis, Protagen AG, Roche, Teva.
The project was supported by the Charles University Grant Agency (GAUK) 230217, Czech Ministry of Education project PRVOUK-P26/LF1/4, Czech Ministry of Health project RVO-VFN64165 and grant NV18-04-00168.
Research grant was provided by Biogen.