Abstract
Objectives: In a prospective phase IV trial of the first-line oral treatment dimethyl fumarate (DMF), we examined dynamics of neurofilament light (NFL) chain in serum, plasma and cerebrospinal fluid (CSF) samples collected over 12 months from relapsing-remitting multiple sclerosis (RRMS) patients. NFL changes were related to disease activity. Methods: We examined NFL levels by single-molecule array in 88 CSF, 348 plasma and 131 sera from treatment-naïve RRMS patients (n=52), healthy controls (n=23) and a placebo group matched by age, sex and NFL (n=52). Plasma/sera were collected at baseline, and 1, 3, 6 and 12 months after DMF. CSF samples were collected at baseline and 12 months after DMF. Results: NFL concentration in CSF, plasma and serum correlated highly (p<0.0001 for all), but plasma levels were only 76.9% of paired serum concentration. After 12 months of DMF treatment, NFL concentration decreased by 73%, 69% and 55% in the CSF, serum and plasma (p<0.0001, respectively). Significant reduction in blood was observed after 6 and 12 months treatment compared with baseline (p<0.01 and p<0.0001, respectively) and to placebo (p<0.0001). Patients with NFL above the 807.5 pg/mL cut-off in CSF had 5.0-times relative risk of disease activity (p<0.001). Conclusions: This study provides Class II evidence that first-line DMF reduces NFL in both blood and CSF after 6 months and normalises CSF levels in 73% of patients. High NFL concentration in CSF after a year reflected disease activity. NFL levels were higher in serum than in plasma, which should be considered when NFL is used as a biomarker.
| Original language | English |
|---|---|
| Journal | Journal of Neurology, Neurosurgery and Psychiatry |
| Volume | 90 |
| Issue number | 12 |
| Pages (from-to) | 1324-1330 |
| ISSN | 0022-3050 |
| DOIs | |
| Publication status | Published - Dec 2019 |
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Keywords
- biomarker
- cerebrospinal fluid
- dimethyl fumarate
- disease modifying therapy
- drug response
- multiple sclerosis
- neurofilament
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Dimethyl fumarate decreases neurofilament light chain in CSF and blood of treatment naïve relapsing MS patients. / Sejbaek, Tobias; Nielsen, Helle Hvilsted; Penner, Natasha; Plavina, Tatiana; Mendoza, Jason P.; Martin, Nellie Anne; Elkjaer, Maria Louise; Ravnborg, Mads Henrik; Illes, Zsolt.
In: Journal of Neurology, Neurosurgery and Psychiatry, Vol. 90, No. 12, 12.2019, p. 1324-1330.Research output: Contribution to journal › Journal article › Research › peer-review
TY - JOUR
T1 - Dimethyl fumarate decreases neurofilament light chain in CSF and blood of treatment naïve relapsing MS patients
AU - Sejbaek, Tobias
AU - Nielsen, Helle Hvilsted
AU - Penner, Natasha
AU - Plavina, Tatiana
AU - Mendoza, Jason P.
AU - Martin, Nellie Anne
AU - Elkjaer, Maria Louise
AU - Ravnborg, Mads Henrik
AU - Illes, Zsolt
PY - 2019/12
Y1 - 2019/12
N2 - Objectives: In a prospective phase IV trial of the first-line oral treatment dimethyl fumarate (DMF), we examined dynamics of neurofilament light (NFL) chain in serum, plasma and cerebrospinal fluid (CSF) samples collected over 12 months from relapsing-remitting multiple sclerosis (RRMS) patients. NFL changes were related to disease activity. Methods: We examined NFL levels by single-molecule array in 88 CSF, 348 plasma and 131 sera from treatment-naïve RRMS patients (n=52), healthy controls (n=23) and a placebo group matched by age, sex and NFL (n=52). Plasma/sera were collected at baseline, and 1, 3, 6 and 12 months after DMF. CSF samples were collected at baseline and 12 months after DMF. Results: NFL concentration in CSF, plasma and serum correlated highly (p<0.0001 for all), but plasma levels were only 76.9% of paired serum concentration. After 12 months of DMF treatment, NFL concentration decreased by 73%, 69% and 55% in the CSF, serum and plasma (p<0.0001, respectively). Significant reduction in blood was observed after 6 and 12 months treatment compared with baseline (p<0.01 and p<0.0001, respectively) and to placebo (p<0.0001). Patients with NFL above the 807.5 pg/mL cut-off in CSF had 5.0-times relative risk of disease activity (p<0.001). Conclusions: This study provides Class II evidence that first-line DMF reduces NFL in both blood and CSF after 6 months and normalises CSF levels in 73% of patients. High NFL concentration in CSF after a year reflected disease activity. NFL levels were higher in serum than in plasma, which should be considered when NFL is used as a biomarker.
AB - Objectives: In a prospective phase IV trial of the first-line oral treatment dimethyl fumarate (DMF), we examined dynamics of neurofilament light (NFL) chain in serum, plasma and cerebrospinal fluid (CSF) samples collected over 12 months from relapsing-remitting multiple sclerosis (RRMS) patients. NFL changes were related to disease activity. Methods: We examined NFL levels by single-molecule array in 88 CSF, 348 plasma and 131 sera from treatment-naïve RRMS patients (n=52), healthy controls (n=23) and a placebo group matched by age, sex and NFL (n=52). Plasma/sera were collected at baseline, and 1, 3, 6 and 12 months after DMF. CSF samples were collected at baseline and 12 months after DMF. Results: NFL concentration in CSF, plasma and serum correlated highly (p<0.0001 for all), but plasma levels were only 76.9% of paired serum concentration. After 12 months of DMF treatment, NFL concentration decreased by 73%, 69% and 55% in the CSF, serum and plasma (p<0.0001, respectively). Significant reduction in blood was observed after 6 and 12 months treatment compared with baseline (p<0.01 and p<0.0001, respectively) and to placebo (p<0.0001). Patients with NFL above the 807.5 pg/mL cut-off in CSF had 5.0-times relative risk of disease activity (p<0.001). Conclusions: This study provides Class II evidence that first-line DMF reduces NFL in both blood and CSF after 6 months and normalises CSF levels in 73% of patients. High NFL concentration in CSF after a year reflected disease activity. NFL levels were higher in serum than in plasma, which should be considered when NFL is used as a biomarker.
KW - biomarker
KW - cerebrospinal fluid
KW - dimethyl fumarate
KW - disease modifying therapy
KW - drug response
KW - multiple sclerosis
KW - neurofilament
U2 - 10.1136/jnnp-2019-321321
DO - 10.1136/jnnp-2019-321321
M3 - Journal article
C2 - 31611264
AN - SCOPUS:85073548885
VL - 90
SP - 1324
EP - 1330
JO - Journal of Neurology, Neurosurgery and Psychiatry
JF - Journal of Neurology, Neurosurgery and Psychiatry
SN - 0022-3050
IS - 12
ER -