Pharmacokinetics and Pharmacodynamics of Natalizumab 6-Week Dosing vs Continued 4-Week Dosing for Relapsing-Remitting Multiple Sclerosis.

Humans Natalizumab / administration & dosage Multiple Sclerosis, Relapsing-Remitting / drug therapy Adult Female Male Middle Aged Young Adult Immunologic Factors / administration & dosage Adolescent Drug Administration Schedule

Journal

Neurology(R) neuroimmunology & neuroinflammation
ISSN: 2332-7812
Titre abrégé: Neurol Neuroimmunol Neuroinflamm
Pays: United States
ID NLM: 101636388

Informations de publication

Date de publication:
Dec 2024
Historique:
medline: 11 10 2024
pubmed: 11 10 2024
entrez: 11 10 2024
Statut: ppublish

Résumé

Exposure to natalizumab, an efficacious treatment for relapsing-remitting multiple sclerosis (RRMS), is associated with increased risk of progressive multifocal leukoencephalopathy (PML). Compared with every-4-week (Q4W) dosing, extended-interval dosing of natalizumab is associated with decreased risk of PML. Clinical efficacy was maintained in the majority of patients switched to every-6-week (Q6W) dosing in the phase 3b NOVA clinical trial. In this article, we report pharmacokinetics (PK) and pharmacodynamics (PD) of Q6W vs Q4W dosing in NOVA. In NOVA study Part 1, participants with RRMS (aged 18-60 years) and Expanded Disability Status Scale score <5.5, who were stable on IV natalizumab Q4W dosing for ≥12 months, were randomized to continue IV Q4W dosing or switched to IV Q6W dosing of natalizumab and followed for 72 weeks. Exploratory outcomes were measurements of trough serum natalizumab concentration, α4-integrin saturation, and soluble vascular cell adhesion molecule-1 (sVCAM-1) concentration. A mixed model of repeated measures was used to estimate mean treatment differences between groups. Patient-level PK and PD data were examined in those with relapse or radiologic disease activity. In NOVA, 486 (Q6W, n = 245; Q4W, n = 241) and 487 (Q6W, n = 246; Q4W, n = 241) participants were included in the PK and PD populations, respectively. Mean trough natalizumab concentrations ranged from 10 to 21 μg/mL (Q6W) and 33-38 μg/mL (Q4W), and mean α4-integrin saturation remained above 65.5% (Q6W) and above 77.9% (Q4W). In the Q6W group, mean sVCAM-1 levels increased 23.6% by week 24 and remained elevated throughout the study, while mean sVCAM-1 levels remained generally stable in the Q4W group. Most participants with T2 lesion activity or relapse activity, in either treatment arm, maintained trough natalizumab levels >10 μg/mL and trough α4-integrin saturation >50%. Compared with Q4W dosing, Q6W dosing was associated with a 60%-70% decrease in mean trough natalizumab levels and a 9%-16% decrease in mean α4-integrin saturation. At the patient level, neither natalizumab concentration nor α4-integrin saturation was consistently predictive of lesion or relapse activity, suggesting that trough natalizumab and α4-integrin saturation measurements should be interpreted with caution in clinical practice. ClinicalTrials.gov, NCT03689972; EudraCT, 2018-002145-11. Submitted 2018-09-27. First patient enrolled: 2018-12-26. https://clinicaltrials.gov/study/NCT03689972.

Sections du résumé

BACKGROUND AND OBJECTIVES OBJECTIVE
Exposure to natalizumab, an efficacious treatment for relapsing-remitting multiple sclerosis (RRMS), is associated with increased risk of progressive multifocal leukoencephalopathy (PML). Compared with every-4-week (Q4W) dosing, extended-interval dosing of natalizumab is associated with decreased risk of PML. Clinical efficacy was maintained in the majority of patients switched to every-6-week (Q6W) dosing in the phase 3b NOVA clinical trial. In this article, we report pharmacokinetics (PK) and pharmacodynamics (PD) of Q6W vs Q4W dosing in NOVA.
METHODS METHODS
In NOVA study Part 1, participants with RRMS (aged 18-60 years) and Expanded Disability Status Scale score <5.5, who were stable on IV natalizumab Q4W dosing for ≥12 months, were randomized to continue IV Q4W dosing or switched to IV Q6W dosing of natalizumab and followed for 72 weeks. Exploratory outcomes were measurements of trough serum natalizumab concentration, α4-integrin saturation, and soluble vascular cell adhesion molecule-1 (sVCAM-1) concentration. A mixed model of repeated measures was used to estimate mean treatment differences between groups. Patient-level PK and PD data were examined in those with relapse or radiologic disease activity.
RESULTS RESULTS
In NOVA, 486 (Q6W, n = 245; Q4W, n = 241) and 487 (Q6W, n = 246; Q4W, n = 241) participants were included in the PK and PD populations, respectively. Mean trough natalizumab concentrations ranged from 10 to 21 μg/mL (Q6W) and 33-38 μg/mL (Q4W), and mean α4-integrin saturation remained above 65.5% (Q6W) and above 77.9% (Q4W). In the Q6W group, mean sVCAM-1 levels increased 23.6% by week 24 and remained elevated throughout the study, while mean sVCAM-1 levels remained generally stable in the Q4W group. Most participants with T2 lesion activity or relapse activity, in either treatment arm, maintained trough natalizumab levels >10 μg/mL and trough α4-integrin saturation >50%.
DISCUSSION CONCLUSIONS
Compared with Q4W dosing, Q6W dosing was associated with a 60%-70% decrease in mean trough natalizumab levels and a 9%-16% decrease in mean α4-integrin saturation. At the patient level, neither natalizumab concentration nor α4-integrin saturation was consistently predictive of lesion or relapse activity, suggesting that trough natalizumab and α4-integrin saturation measurements should be interpreted with caution in clinical practice.
TRIAL REGISTRATION INFORMATION UNASSIGNED
ClinicalTrials.gov, NCT03689972; EudraCT, 2018-002145-11. Submitted 2018-09-27. First patient enrolled: 2018-12-26. https://clinicaltrials.gov/study/NCT03689972.

Identifiants

DOI: 10.1212/NXI.0000000000200321 PMID: 39393045
pubmed: 39393045
doi: 10.1212/NXI.0000000000200321
doi:

Substances chimiques

Natalizumab 0
Immunologic Factors 0

Banques de données

ClinicalTrials.gov
['NCT03689972']

Types de publication

Journal Article Randomized Controlled Trial Clinical Trial, Phase III Multicenter Study

Langues

eng

Sous-ensembles de citation

IM

Pagination

e200321

Auteurs

John F Foley (JF)

From the Rocky Mountain MS Clinic (J.F.F.), Salt Lake City, UT; Department of Neurology (G.D.), Centre Hospitalier Universitaire de Caen, France; Hackensack Meridian Medical Group - Neurology (L.Z.R.), Jersey Shore University Medical Center, Neptune City, NJ; Mellen MS Center (J.A.C.), Neurological Institute, Cleveland Clinic, OH; Montréal Neurological Institute (D.L.A.), McGill University; NeuroRx Research (D.L.A.), Montréal, Quebec, Canada; Department of Neuroscience (H.B.), Central Clinical School, Monash University, Melbourne, Victoria, Australia; University of Alabama at Birmingham (G.R.C.), School of Public Health; Blizard Institute (G.G.), Barts and The London School of Medicine and Dentistry; Queen Mary University of London (G.G.), United Kingdom; Department of Neurology (J.K.), Amsterdam University Medical Centers, Vrije Universiteit, Netherlands; Department of Neurology with Institute of Translational Neurology (H.W.), University of Münster, Germany; Biogen (K.L., L.D., M.T., K.F., J.S., T.L.), Cambridge, MA; and Ashfield MedComms (H.E.), Middletown, CT.

Gilles Defer (G)

From the Rocky Mountain MS Clinic (J.F.F.), Salt Lake City, UT; Department of Neurology (G.D.), Centre Hospitalier Universitaire de Caen, France; Hackensack Meridian Medical Group - Neurology (L.Z.R.), Jersey Shore University Medical Center, Neptune City, NJ; Mellen MS Center (J.A.C.), Neurological Institute, Cleveland Clinic, OH; Montréal Neurological Institute (D.L.A.), McGill University; NeuroRx Research (D.L.A.), Montréal, Quebec, Canada; Department of Neuroscience (H.B.), Central Clinical School, Monash University, Melbourne, Victoria, Australia; University of Alabama at Birmingham (G.R.C.), School of Public Health; Blizard Institute (G.G.), Barts and The London School of Medicine and Dentistry; Queen Mary University of London (G.G.), United Kingdom; Department of Neurology (J.K.), Amsterdam University Medical Centers, Vrije Universiteit, Netherlands; Department of Neurology with Institute of Translational Neurology (H.W.), University of Münster, Germany; Biogen (K.L., L.D., M.T., K.F., J.S., T.L.), Cambridge, MA; and Ashfield MedComms (H.E.), Middletown, CT.
ORCID: 0000-0003-1343-5858

Lana Zhovtis Ryerson (LZ)

From the Rocky Mountain MS Clinic (J.F.F.), Salt Lake City, UT; Department of Neurology (G.D.), Centre Hospitalier Universitaire de Caen, France; Hackensack Meridian Medical Group - Neurology (L.Z.R.), Jersey Shore University Medical Center, Neptune City, NJ; Mellen MS Center (J.A.C.), Neurological Institute, Cleveland Clinic, OH; Montréal Neurological Institute (D.L.A.), McGill University; NeuroRx Research (D.L.A.), Montréal, Quebec, Canada; Department of Neuroscience (H.B.), Central Clinical School, Monash University, Melbourne, Victoria, Australia; University of Alabama at Birmingham (G.R.C.), School of Public Health; Blizard Institute (G.G.), Barts and The London School of Medicine and Dentistry; Queen Mary University of London (G.G.), United Kingdom; Department of Neurology (J.K.), Amsterdam University Medical Centers, Vrije Universiteit, Netherlands; Department of Neurology with Institute of Translational Neurology (H.W.), University of Münster, Germany; Biogen (K.L., L.D., M.T., K.F., J.S., T.L.), Cambridge, MA; and Ashfield MedComms (H.E.), Middletown, CT.

Jeffrey A Cohen (JA)

From the Rocky Mountain MS Clinic (J.F.F.), Salt Lake City, UT; Department of Neurology (G.D.), Centre Hospitalier Universitaire de Caen, France; Hackensack Meridian Medical Group - Neurology (L.Z.R.), Jersey Shore University Medical Center, Neptune City, NJ; Mellen MS Center (J.A.C.), Neurological Institute, Cleveland Clinic, OH; Montréal Neurological Institute (D.L.A.), McGill University; NeuroRx Research (D.L.A.), Montréal, Quebec, Canada; Department of Neuroscience (H.B.), Central Clinical School, Monash University, Melbourne, Victoria, Australia; University of Alabama at Birmingham (G.R.C.), School of Public Health; Blizard Institute (G.G.), Barts and The London School of Medicine and Dentistry; Queen Mary University of London (G.G.), United Kingdom; Department of Neurology (J.K.), Amsterdam University Medical Centers, Vrije Universiteit, Netherlands; Department of Neurology with Institute of Translational Neurology (H.W.), University of Münster, Germany; Biogen (K.L., L.D., M.T., K.F., J.S., T.L.), Cambridge, MA; and Ashfield MedComms (H.E.), Middletown, CT.
ORCID: 0000-0001-9245-9772

Douglas L Arnold (DL)

From the Rocky Mountain MS Clinic (J.F.F.), Salt Lake City, UT; Department of Neurology (G.D.), Centre Hospitalier Universitaire de Caen, France; Hackensack Meridian Medical Group - Neurology (L.Z.R.), Jersey Shore University Medical Center, Neptune City, NJ; Mellen MS Center (J.A.C.), Neurological Institute, Cleveland Clinic, OH; Montréal Neurological Institute (D.L.A.), McGill University; NeuroRx Research (D.L.A.), Montréal, Quebec, Canada; Department of Neuroscience (H.B.), Central Clinical School, Monash University, Melbourne, Victoria, Australia; University of Alabama at Birmingham (G.R.C.), School of Public Health; Blizard Institute (G.G.), Barts and The London School of Medicine and Dentistry; Queen Mary University of London (G.G.), United Kingdom; Department of Neurology (J.K.), Amsterdam University Medical Centers, Vrije Universiteit, Netherlands; Department of Neurology with Institute of Translational Neurology (H.W.), University of Münster, Germany; Biogen (K.L., L.D., M.T., K.F., J.S., T.L.), Cambridge, MA; and Ashfield MedComms (H.E.), Middletown, CT.
ORCID: 0000-0003-4266-0106

Helmut Butzkueven (H)

From the Rocky Mountain MS Clinic (J.F.F.), Salt Lake City, UT; Department of Neurology (G.D.), Centre Hospitalier Universitaire de Caen, France; Hackensack Meridian Medical Group - Neurology (L.Z.R.), Jersey Shore University Medical Center, Neptune City, NJ; Mellen MS Center (J.A.C.), Neurological Institute, Cleveland Clinic, OH; Montréal Neurological Institute (D.L.A.), McGill University; NeuroRx Research (D.L.A.), Montréal, Quebec, Canada; Department of Neuroscience (H.B.), Central Clinical School, Monash University, Melbourne, Victoria, Australia; University of Alabama at Birmingham (G.R.C.), School of Public Health; Blizard Institute (G.G.), Barts and The London School of Medicine and Dentistry; Queen Mary University of London (G.G.), United Kingdom; Department of Neurology (J.K.), Amsterdam University Medical Centers, Vrije Universiteit, Netherlands; Department of Neurology with Institute of Translational Neurology (H.W.), University of Münster, Germany; Biogen (K.L., L.D., M.T., K.F., J.S., T.L.), Cambridge, MA; and Ashfield MedComms (H.E.), Middletown, CT.
ORCID: 0000-0003-3940-8727

Gary R Cutter (GR)

From the Rocky Mountain MS Clinic (J.F.F.), Salt Lake City, UT; Department of Neurology (G.D.), Centre Hospitalier Universitaire de Caen, France; Hackensack Meridian Medical Group - Neurology (L.Z.R.), Jersey Shore University Medical Center, Neptune City, NJ; Mellen MS Center (J.A.C.), Neurological Institute, Cleveland Clinic, OH; Montréal Neurological Institute (D.L.A.), McGill University; NeuroRx Research (D.L.A.), Montréal, Quebec, Canada; Department of Neuroscience (H.B.), Central Clinical School, Monash University, Melbourne, Victoria, Australia; University of Alabama at Birmingham (G.R.C.), School of Public Health; Blizard Institute (G.G.), Barts and The London School of Medicine and Dentistry; Queen Mary University of London (G.G.), United Kingdom; Department of Neurology (J.K.), Amsterdam University Medical Centers, Vrije Universiteit, Netherlands; Department of Neurology with Institute of Translational Neurology (H.W.), University of Münster, Germany; Biogen (K.L., L.D., M.T., K.F., J.S., T.L.), Cambridge, MA; and Ashfield MedComms (H.E.), Middletown, CT.
ORCID: 0000-0002-8455-980X

Gavin Giovannoni (G)

From the Rocky Mountain MS Clinic (J.F.F.), Salt Lake City, UT; Department of Neurology (G.D.), Centre Hospitalier Universitaire de Caen, France; Hackensack Meridian Medical Group - Neurology (L.Z.R.), Jersey Shore University Medical Center, Neptune City, NJ; Mellen MS Center (J.A.C.), Neurological Institute, Cleveland Clinic, OH; Montréal Neurological Institute (D.L.A.), McGill University; NeuroRx Research (D.L.A.), Montréal, Quebec, Canada; Department of Neuroscience (H.B.), Central Clinical School, Monash University, Melbourne, Victoria, Australia; University of Alabama at Birmingham (G.R.C.), School of Public Health; Blizard Institute (G.G.), Barts and The London School of Medicine and Dentistry; Queen Mary University of London (G.G.), United Kingdom; Department of Neurology (J.K.), Amsterdam University Medical Centers, Vrije Universiteit, Netherlands; Department of Neurology with Institute of Translational Neurology (H.W.), University of Münster, Germany; Biogen (K.L., L.D., M.T., K.F., J.S., T.L.), Cambridge, MA; and Ashfield MedComms (H.E.), Middletown, CT.
ORCID: 0000-0001-9995-1700

Joep Killestein (J)

From the Rocky Mountain MS Clinic (J.F.F.), Salt Lake City, UT; Department of Neurology (G.D.), Centre Hospitalier Universitaire de Caen, France; Hackensack Meridian Medical Group - Neurology (L.Z.R.), Jersey Shore University Medical Center, Neptune City, NJ; Mellen MS Center (J.A.C.), Neurological Institute, Cleveland Clinic, OH; Montréal Neurological Institute (D.L.A.), McGill University; NeuroRx Research (D.L.A.), Montréal, Quebec, Canada; Department of Neuroscience (H.B.), Central Clinical School, Monash University, Melbourne, Victoria, Australia; University of Alabama at Birmingham (G.R.C.), School of Public Health; Blizard Institute (G.G.), Barts and The London School of Medicine and Dentistry; Queen Mary University of London (G.G.), United Kingdom; Department of Neurology (J.K.), Amsterdam University Medical Centers, Vrije Universiteit, Netherlands; Department of Neurology with Institute of Translational Neurology (H.W.), University of Münster, Germany; Biogen (K.L., L.D., M.T., K.F., J.S., T.L.), Cambridge, MA; and Ashfield MedComms (H.E.), Middletown, CT.
ORCID: 0000-0002-6347-5957

Heinz Wiendl (H)

From the Rocky Mountain MS Clinic (J.F.F.), Salt Lake City, UT; Department of Neurology (G.D.), Centre Hospitalier Universitaire de Caen, France; Hackensack Meridian Medical Group - Neurology (L.Z.R.), Jersey Shore University Medical Center, Neptune City, NJ; Mellen MS Center (J.A.C.), Neurological Institute, Cleveland Clinic, OH; Montréal Neurological Institute (D.L.A.), McGill University; NeuroRx Research (D.L.A.), Montréal, Quebec, Canada; Department of Neuroscience (H.B.), Central Clinical School, Monash University, Melbourne, Victoria, Australia; University of Alabama at Birmingham (G.R.C.), School of Public Health; Blizard Institute (G.G.), Barts and The London School of Medicine and Dentistry; Queen Mary University of London (G.G.), United Kingdom; Department of Neurology (J.K.), Amsterdam University Medical Centers, Vrije Universiteit, Netherlands; Department of Neurology with Institute of Translational Neurology (H.W.), University of Münster, Germany; Biogen (K.L., L.D., M.T., K.F., J.S., T.L.), Cambridge, MA; and Ashfield MedComms (H.E.), Middletown, CT.
ORCID: 0000-0003-4310-3432

Kexuan Li (K)

From the Rocky Mountain MS Clinic (J.F.F.), Salt Lake City, UT; Department of Neurology (G.D.), Centre Hospitalier Universitaire de Caen, France; Hackensack Meridian Medical Group - Neurology (L.Z.R.), Jersey Shore University Medical Center, Neptune City, NJ; Mellen MS Center (J.A.C.), Neurological Institute, Cleveland Clinic, OH; Montréal Neurological Institute (D.L.A.), McGill University; NeuroRx Research (D.L.A.), Montréal, Quebec, Canada; Department of Neuroscience (H.B.), Central Clinical School, Monash University, Melbourne, Victoria, Australia; University of Alabama at Birmingham (G.R.C.), School of Public Health; Blizard Institute (G.G.), Barts and The London School of Medicine and Dentistry; Queen Mary University of London (G.G.), United Kingdom; Department of Neurology (J.K.), Amsterdam University Medical Centers, Vrije Universiteit, Netherlands; Department of Neurology with Institute of Translational Neurology (H.W.), University of Münster, Germany; Biogen (K.L., L.D., M.T., K.F., J.S., T.L.), Cambridge, MA; and Ashfield MedComms (H.E.), Middletown, CT.

Liesel Dsilva (L)

From the Rocky Mountain MS Clinic (J.F.F.), Salt Lake City, UT; Department of Neurology (G.D.), Centre Hospitalier Universitaire de Caen, France; Hackensack Meridian Medical Group - Neurology (L.Z.R.), Jersey Shore University Medical Center, Neptune City, NJ; Mellen MS Center (J.A.C.), Neurological Institute, Cleveland Clinic, OH; Montréal Neurological Institute (D.L.A.), McGill University; NeuroRx Research (D.L.A.), Montréal, Quebec, Canada; Department of Neuroscience (H.B.), Central Clinical School, Monash University, Melbourne, Victoria, Australia; University of Alabama at Birmingham (G.R.C.), School of Public Health; Blizard Institute (G.G.), Barts and The London School of Medicine and Dentistry; Queen Mary University of London (G.G.), United Kingdom; Department of Neurology (J.K.), Amsterdam University Medical Centers, Vrije Universiteit, Netherlands; Department of Neurology with Institute of Translational Neurology (H.W.), University of Münster, Germany; Biogen (K.L., L.D., M.T., K.F., J.S., T.L.), Cambridge, MA; and Ashfield MedComms (H.E.), Middletown, CT.

Marie Toukam (M)

From the Rocky Mountain MS Clinic (J.F.F.), Salt Lake City, UT; Department of Neurology (G.D.), Centre Hospitalier Universitaire de Caen, France; Hackensack Meridian Medical Group - Neurology (L.Z.R.), Jersey Shore University Medical Center, Neptune City, NJ; Mellen MS Center (J.A.C.), Neurological Institute, Cleveland Clinic, OH; Montréal Neurological Institute (D.L.A.), McGill University; NeuroRx Research (D.L.A.), Montréal, Quebec, Canada; Department of Neuroscience (H.B.), Central Clinical School, Monash University, Melbourne, Victoria, Australia; University of Alabama at Birmingham (G.R.C.), School of Public Health; Blizard Institute (G.G.), Barts and The London School of Medicine and Dentistry; Queen Mary University of London (G.G.), United Kingdom; Department of Neurology (J.K.), Amsterdam University Medical Centers, Vrije Universiteit, Netherlands; Department of Neurology with Institute of Translational Neurology (H.W.), University of Münster, Germany; Biogen (K.L., L.D., M.T., K.F., J.S., T.L.), Cambridge, MA; and Ashfield MedComms (H.E.), Middletown, CT.

Kyle Ferber (K)

From the Rocky Mountain MS Clinic (J.F.F.), Salt Lake City, UT; Department of Neurology (G.D.), Centre Hospitalier Universitaire de Caen, France; Hackensack Meridian Medical Group - Neurology (L.Z.R.), Jersey Shore University Medical Center, Neptune City, NJ; Mellen MS Center (J.A.C.), Neurological Institute, Cleveland Clinic, OH; Montréal Neurological Institute (D.L.A.), McGill University; NeuroRx Research (D.L.A.), Montréal, Quebec, Canada; Department of Neuroscience (H.B.), Central Clinical School, Monash University, Melbourne, Victoria, Australia; University of Alabama at Birmingham (G.R.C.), School of Public Health; Blizard Institute (G.G.), Barts and The London School of Medicine and Dentistry; Queen Mary University of London (G.G.), United Kingdom; Department of Neurology (J.K.), Amsterdam University Medical Centers, Vrije Universiteit, Netherlands; Department of Neurology with Institute of Translational Neurology (H.W.), University of Münster, Germany; Biogen (K.L., L.D., M.T., K.F., J.S., T.L.), Cambridge, MA; and Ashfield MedComms (H.E.), Middletown, CT.

Jihee Sohn (J)

From the Rocky Mountain MS Clinic (J.F.F.), Salt Lake City, UT; Department of Neurology (G.D.), Centre Hospitalier Universitaire de Caen, France; Hackensack Meridian Medical Group - Neurology (L.Z.R.), Jersey Shore University Medical Center, Neptune City, NJ; Mellen MS Center (J.A.C.), Neurological Institute, Cleveland Clinic, OH; Montréal Neurological Institute (D.L.A.), McGill University; NeuroRx Research (D.L.A.), Montréal, Quebec, Canada; Department of Neuroscience (H.B.), Central Clinical School, Monash University, Melbourne, Victoria, Australia; University of Alabama at Birmingham (G.R.C.), School of Public Health; Blizard Institute (G.G.), Barts and The London School of Medicine and Dentistry; Queen Mary University of London (G.G.), United Kingdom; Department of Neurology (J.K.), Amsterdam University Medical Centers, Vrije Universiteit, Netherlands; Department of Neurology with Institute of Translational Neurology (H.W.), University of Münster, Germany; Biogen (K.L., L.D., M.T., K.F., J.S., T.L.), Cambridge, MA; and Ashfield MedComms (H.E.), Middletown, CT.

Holly Engelman (H)

From the Rocky Mountain MS Clinic (J.F.F.), Salt Lake City, UT; Department of Neurology (G.D.), Centre Hospitalier Universitaire de Caen, France; Hackensack Meridian Medical Group - Neurology (L.Z.R.), Jersey Shore University Medical Center, Neptune City, NJ; Mellen MS Center (J.A.C.), Neurological Institute, Cleveland Clinic, OH; Montréal Neurological Institute (D.L.A.), McGill University; NeuroRx Research (D.L.A.), Montréal, Quebec, Canada; Department of Neuroscience (H.B.), Central Clinical School, Monash University, Melbourne, Victoria, Australia; University of Alabama at Birmingham (G.R.C.), School of Public Health; Blizard Institute (G.G.), Barts and The London School of Medicine and Dentistry; Queen Mary University of London (G.G.), United Kingdom; Department of Neurology (J.K.), Amsterdam University Medical Centers, Vrije Universiteit, Netherlands; Department of Neurology with Institute of Translational Neurology (H.W.), University of Münster, Germany; Biogen (K.L., L.D., M.T., K.F., J.S., T.L.), Cambridge, MA; and Ashfield MedComms (H.E.), Middletown, CT.

Tyler Lasky (T)

From the Rocky Mountain MS Clinic (J.F.F.), Salt Lake City, UT; Department of Neurology (G.D.), Centre Hospitalier Universitaire de Caen, France; Hackensack Meridian Medical Group - Neurology (L.Z.R.), Jersey Shore University Medical Center, Neptune City, NJ; Mellen MS Center (J.A.C.), Neurological Institute, Cleveland Clinic, OH; Montréal Neurological Institute (D.L.A.), McGill University; NeuroRx Research (D.L.A.), Montréal, Quebec, Canada; Department of Neuroscience (H.B.), Central Clinical School, Monash University, Melbourne, Victoria, Australia; University of Alabama at Birmingham (G.R.C.), School of Public Health; Blizard Institute (G.G.), Barts and The London School of Medicine and Dentistry; Queen Mary University of London (G.G.), United Kingdom; Department of Neurology (J.K.), Amsterdam University Medical Centers, Vrije Universiteit, Netherlands; Department of Neurology with Institute of Translational Neurology (H.W.), University of Münster, Germany; Biogen (K.L., L.D., M.T., K.F., J.S., T.L.), Cambridge, MA; and Ashfield MedComms (H.E.), Middletown, CT.

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