Contributions
Abstract: P852
Type: Poster Sessions
Abstract Category: Pathology and pathogenesis of MS - Biomarkers
Background: Neurofilament light chain (NfL) is an emerging biomarker of disease activity that has been shown to predict outcome and treatment response in relapsing-remitting multiple sclerosis (RRMS). Dimethyl fumarate (DMF) is an approved treatment for relapsing MS.
Objectives: To examine changes in plasma, serum and cerebrospinal fluid (CSF) NfL levels in RRMS patients after treatment with DMF.
Methods: In the TREMEND clinical study, a prospective phase IV trial, plasma, serum and CSF (optional) were collected from newly diagnosed treatment-naïve RRMS-patients (n=52) and healthy controls (HC, n=28). Plasma/sera were collected at baseline (BL), and at 1, 3, 6 and 12 months after initiation of DMF treatment. CSF samples were collected at baseline and 12 months. Sera from a matched placebo control group from the ADVANCE trial (n=100, baseline and 12 months) were used for comparisons. NfL concentration was measured using a sensitive Single Molecular Array (SIMOA) assay (Quanterix).
Results: Pre-treatment CSF NfL concentrations were higher in MS patients compared to HC (mean±SD 2368±1947 pg/ml versus 417±191 pg/ml, p< 0.001). ROC analysis defined a cutoff value of 808 pg/ml to differentiate MS from HC (80 % sensitivity and 100 % specificity), and a cutoff value of 13.0 pg/ml (47% sensitivity and 100% specificity), for CSF NfL and plasma NfL, respectively. There was a high correlation between NfL concentration in the CSF, plasma and serum (RCSF/p:0.79, p< 0.0001; RCSF/s:0.72, p< 0.0001; Rp/s:0.97, p< 0.0001). After 12 months of DMF treatment, NfL concentration decreased by 73% in CSF and 55% in plasma (p< 0.0001 for both). The placebo group demonstrated no change in serum NfL from baseline to 12 months (p=0.71). Significant reduction in plasma levels was observed after 6 months (p< 0.01) and 12 months (p< 0.0001) of DMF treatment compared to baseline. Plasma NfL-levels 12 months after DMF treatment were lower compared to placebo (p=0.001) and no different than HC. Patients with NfL above 808 pg/ml in CSF had a relative risk of 3.25 of experiencing disease activity compared to those below the cutoff (p< 0.03). No significant difference in risk of disease activity was observed for patients with plasma NfL levels below and above threshold of 13.0 pg/ml.
Conclusions: Plasma NfL decreased after 6 months treatment with DMF and stayed low in contrast to a matched placebo cohort. NfL levels in CSF after 12 months of DMF treatment reflected disease activity within the first year.
Disclosure: This study was supported by Biogen (Cambridge, MA, USA)
Dr. Sejbaek has served on scientific advisory boards, received support for congress participation, received speaker honoraria, and received research support from Biogen, Merck-Serono, Lundbeck, Novartis and Teva
Dr. Penner: employee of and holds stock/stock options in Biogen
Dr. Plavina: employee of and holds stock/stock options in Biogen
Dr. Mendoza: employee of and holds stock/stock options in Biogen
Dr. Sangurdekar: employee of and holds stock/stock options in Biogen
Dr. Nielsen has served on scientific advisory boards, received support for congress participation, received speaker honoraria, and received research support from Biogen, Merck-Serono, Lundbeck, and Novartis
MSc Martin has nothing to disclose
MSc Elkjaer has nothing to disclose
Dr. Ravnborg has nothing to disclose
Dr. Illes has served on scientific advisory boards, served as a consultant, received support for congress participation, received speaker honoraria, and received research support from Biogen, Merck-Serono, Sanofi-Genzyme, Lundbeck, and Novartis.
Abstract: P852
Type: Poster Sessions
Abstract Category: Pathology and pathogenesis of MS - Biomarkers
Background: Neurofilament light chain (NfL) is an emerging biomarker of disease activity that has been shown to predict outcome and treatment response in relapsing-remitting multiple sclerosis (RRMS). Dimethyl fumarate (DMF) is an approved treatment for relapsing MS.
Objectives: To examine changes in plasma, serum and cerebrospinal fluid (CSF) NfL levels in RRMS patients after treatment with DMF.
Methods: In the TREMEND clinical study, a prospective phase IV trial, plasma, serum and CSF (optional) were collected from newly diagnosed treatment-naïve RRMS-patients (n=52) and healthy controls (HC, n=28). Plasma/sera were collected at baseline (BL), and at 1, 3, 6 and 12 months after initiation of DMF treatment. CSF samples were collected at baseline and 12 months. Sera from a matched placebo control group from the ADVANCE trial (n=100, baseline and 12 months) were used for comparisons. NfL concentration was measured using a sensitive Single Molecular Array (SIMOA) assay (Quanterix).
Results: Pre-treatment CSF NfL concentrations were higher in MS patients compared to HC (mean±SD 2368±1947 pg/ml versus 417±191 pg/ml, p< 0.001). ROC analysis defined a cutoff value of 808 pg/ml to differentiate MS from HC (80 % sensitivity and 100 % specificity), and a cutoff value of 13.0 pg/ml (47% sensitivity and 100% specificity), for CSF NfL and plasma NfL, respectively. There was a high correlation between NfL concentration in the CSF, plasma and serum (RCSF/p:0.79, p< 0.0001; RCSF/s:0.72, p< 0.0001; Rp/s:0.97, p< 0.0001). After 12 months of DMF treatment, NfL concentration decreased by 73% in CSF and 55% in plasma (p< 0.0001 for both). The placebo group demonstrated no change in serum NfL from baseline to 12 months (p=0.71). Significant reduction in plasma levels was observed after 6 months (p< 0.01) and 12 months (p< 0.0001) of DMF treatment compared to baseline. Plasma NfL-levels 12 months after DMF treatment were lower compared to placebo (p=0.001) and no different than HC. Patients with NfL above 808 pg/ml in CSF had a relative risk of 3.25 of experiencing disease activity compared to those below the cutoff (p< 0.03). No significant difference in risk of disease activity was observed for patients with plasma NfL levels below and above threshold of 13.0 pg/ml.
Conclusions: Plasma NfL decreased after 6 months treatment with DMF and stayed low in contrast to a matched placebo cohort. NfL levels in CSF after 12 months of DMF treatment reflected disease activity within the first year.
Disclosure: This study was supported by Biogen (Cambridge, MA, USA)
Dr. Sejbaek has served on scientific advisory boards, received support for congress participation, received speaker honoraria, and received research support from Biogen, Merck-Serono, Lundbeck, Novartis and Teva
Dr. Penner: employee of and holds stock/stock options in Biogen
Dr. Plavina: employee of and holds stock/stock options in Biogen
Dr. Mendoza: employee of and holds stock/stock options in Biogen
Dr. Sangurdekar: employee of and holds stock/stock options in Biogen
Dr. Nielsen has served on scientific advisory boards, received support for congress participation, received speaker honoraria, and received research support from Biogen, Merck-Serono, Lundbeck, and Novartis
MSc Martin has nothing to disclose
MSc Elkjaer has nothing to disclose
Dr. Ravnborg has nothing to disclose
Dr. Illes has served on scientific advisory boards, served as a consultant, received support for congress participation, received speaker honoraria, and received research support from Biogen, Merck-Serono, Sanofi-Genzyme, Lundbeck, and Novartis.