Serum neurofilament light chain is associated with MS outcomes and comorbidity in a large population of people with multiple sclerosis
ECTRIMS Online Library. Fitzgerald K. 09/11/19; 279375; 23
Kathryn Fitzgerald
Kathryn Fitzgerald
Contributions
Abstract

Abstract: 23

Type: Young Scientific Investigators' Session

Abstract Category: Pathology and pathogenesis of MS - Biomarkers

K. Fitzgerald1, E. Sotirchos2, M. Smith2, C. de Moor3, J. Williams3, C. Singh4, T. Plavina3, R. Rudick3, P. Calabresi2, E. Mowry1

1Neurology, Johns Hopkins School of Medicine, 2Neurology, Johns Hopkins University, Baltimore, MD, 3Biogen, Cambridge, MA, 4Biogen, Cambridge, MD, United States

Introduction: Serum neurofilament light chain (sNfL) is a promising biomarker for measuring disease activity and severity in multiple sclerosis (MS). Evaluation of sNfL in large, heterogeneous MS populations with more diverse demographics and comorbid conditions is sparse.
Objectives: To assess the association between sNfL and MS demographic and disease characteristics as well as the impact of comorbidities on sNfL levels in a large heterogeneous cohort of MS patients.
Methods: The MS Partners Advancing Technology and Health Solutions (MS PATHS) program is a network of MS Centers in the United States (7) and Europe (3). Standardized collection of clinical information and biosamples are acquired during routine clinic visits. sNfL levels were measured in serum samples from 1969 MS PATHS MS patients, and in 130 local healthy controls (HC) via Single Molecule Array (SIMOA, NF-light® Advantage, Quanterix). Age-specific cut-points of sNfL levels were derived from HC data; patients with sNfL levels ≥ or < the age-specific 97.5th percentile in HCs were classified as having elevated sNfL (sNfL-E) or normal sNfL (sNfL-N), respectively. MS patients with sNfL-E vs. sNfL-N were compared with respect to walking speed, manual dexterity, and processing speed using linear models (GLMs) adjusting for age, sex, disease subtype/duration and MS therapy. We assessed whether sNfL differed by race or by comorbidity status using multivariable GLMs that also adjusted for disability.
Results: Of the 1969 MS patients (74% female; mean age 48y [SD: 12.0y]; 18% non-white), 483 (25%) participants were classified as sNfL-E. Relative to sNfL-N, MS patients with sNfL-E had slower walking and manual dexterity speeds (mean %difference [95% CI]: walking speed: 10% slower [6%, 14%]; p< 0.001; manual dexterity: 7% slower [5%, 10%]; p< 0.001) and lower processing speed scores (mean difference -3.78 [-4.84, -2.70]; p< 0.001). Diabetics were more likely to have sNfL-E (OR: 2.24; 95%CI: 1.41, 3.58; p=0.0007). The cross-sectional association between obesity and sNfL was complex and may vary by disability. sNfL levels did not differ by race or in patients with hyperlipidemia, hypertension or renal insufficiency (all p>0.05).
Conclusions: In this large, real-world cross-sectional study of people with MS, elevated sNfL was associated with poorer neurologic function and with diabetes. Follow-up studies are needed to assess if comorbidities modify longitudinal associations between sNfL and MS outcomes.
Disclosure: MS PATHS is supported by Biogen.
Kathryn Fitzgerald, Elias Sotirchos and Mathew Smith have nothing to disclose.
Ellen Mowry has grants from Biogen and Genzyme, is site PI for studies sponsored by Biogen and Sun Pharma, has received free medication for a clinical trial from Teva and receives royalties for editorial duties from UpToDate.
Peter Calabresi has received consulting fees from Disarm Therapeutics and Biogen and is PI on grants to JHU from Biogen and Annexon.
Andreas Jeromin is a scientific and medical advisor to Quanterix Corp and holds stock options.
Elizabeth Fisher, Carl de Moor, James Williams, Tatiana Plavina, Richard Rudick are employees of Biogen and hold stock/stock options in the company;

Abstract: 23

Type: Young Scientific Investigators' Session

Abstract Category: Pathology and pathogenesis of MS - Biomarkers

K. Fitzgerald1, E. Sotirchos2, M. Smith2, C. de Moor3, J. Williams3, C. Singh4, T. Plavina3, R. Rudick3, P. Calabresi2, E. Mowry1

1Neurology, Johns Hopkins School of Medicine, 2Neurology, Johns Hopkins University, Baltimore, MD, 3Biogen, Cambridge, MA, 4Biogen, Cambridge, MD, United States

Introduction: Serum neurofilament light chain (sNfL) is a promising biomarker for measuring disease activity and severity in multiple sclerosis (MS). Evaluation of sNfL in large, heterogeneous MS populations with more diverse demographics and comorbid conditions is sparse.
Objectives: To assess the association between sNfL and MS demographic and disease characteristics as well as the impact of comorbidities on sNfL levels in a large heterogeneous cohort of MS patients.
Methods: The MS Partners Advancing Technology and Health Solutions (MS PATHS) program is a network of MS Centers in the United States (7) and Europe (3). Standardized collection of clinical information and biosamples are acquired during routine clinic visits. sNfL levels were measured in serum samples from 1969 MS PATHS MS patients, and in 130 local healthy controls (HC) via Single Molecule Array (SIMOA, NF-light® Advantage, Quanterix). Age-specific cut-points of sNfL levels were derived from HC data; patients with sNfL levels ≥ or < the age-specific 97.5th percentile in HCs were classified as having elevated sNfL (sNfL-E) or normal sNfL (sNfL-N), respectively. MS patients with sNfL-E vs. sNfL-N were compared with respect to walking speed, manual dexterity, and processing speed using linear models (GLMs) adjusting for age, sex, disease subtype/duration and MS therapy. We assessed whether sNfL differed by race or by comorbidity status using multivariable GLMs that also adjusted for disability.
Results: Of the 1969 MS patients (74% female; mean age 48y [SD: 12.0y]; 18% non-white), 483 (25%) participants were classified as sNfL-E. Relative to sNfL-N, MS patients with sNfL-E had slower walking and manual dexterity speeds (mean %difference [95% CI]: walking speed: 10% slower [6%, 14%]; p< 0.001; manual dexterity: 7% slower [5%, 10%]; p< 0.001) and lower processing speed scores (mean difference -3.78 [-4.84, -2.70]; p< 0.001). Diabetics were more likely to have sNfL-E (OR: 2.24; 95%CI: 1.41, 3.58; p=0.0007). The cross-sectional association between obesity and sNfL was complex and may vary by disability. sNfL levels did not differ by race or in patients with hyperlipidemia, hypertension or renal insufficiency (all p>0.05).
Conclusions: In this large, real-world cross-sectional study of people with MS, elevated sNfL was associated with poorer neurologic function and with diabetes. Follow-up studies are needed to assess if comorbidities modify longitudinal associations between sNfL and MS outcomes.
Disclosure: MS PATHS is supported by Biogen.
Kathryn Fitzgerald, Elias Sotirchos and Mathew Smith have nothing to disclose.
Ellen Mowry has grants from Biogen and Genzyme, is site PI for studies sponsored by Biogen and Sun Pharma, has received free medication for a clinical trial from Teva and receives royalties for editorial duties from UpToDate.
Peter Calabresi has received consulting fees from Disarm Therapeutics and Biogen and is PI on grants to JHU from Biogen and Annexon.
Andreas Jeromin is a scientific and medical advisor to Quanterix Corp and holds stock options.
Elizabeth Fisher, Carl de Moor, James Williams, Tatiana Plavina, Richard Rudick are employees of Biogen and hold stock/stock options in the company;

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