Article Information
Accepted for Publication: December 8, 2023.
Published Online: March 11, 2024. doi:10.1001/jamaneurol.2024.0017
Open Access: This is an open access article distributed under the terms of the
CC-BY-NC-ND License. © 2024 Cross AH et al.
JAMA Neurology.
Corresponding Author: Amit Bar-Or, MD, Department of Neurology, Perelman School of Medicine, University
of Pennsylvania, 3400 Spruce St, 3 Gates Building, Philadelphia, PA 19104 (
amitbar@
123456pennmedicine.upenn.edu
).
Author Contributions: Dr Bar-Or had full access to all of the data in the study and takes responsibility
for the integrity of the data and the accuracy of the data analysis.
Concept and design: Cross, Gelfand, Bennett, von Büdingen, Hafler, Musch, Weber, Freedman, Anania, Winger,
Herman, Harp, Bar-Or.
Acquisition, analysis, or interpretation of data: Cross, Gelfand, Thebault, Cameron, Carruthers, Edwards, Fallis, Gerstein, Giacomini,
Greenberg, Hafler, Ionete, Kaunzner, Kodama, Lock, Longbrake, Pardo, Piehl, Yuen,
Ziemssen, Bose, Freedman, Anania, Ramesh, Winger, Jia, Herman, Harp, Bar-Or.
Drafting of the manuscript: Cross, Thebault, Cameron, Anania, Winger, Jia, Herman, Harp, Bar-Or.
Critical review of the manuscript for important intellectual content: Gelfand, Bennett, von Büdingen, Carruthers, Edwards, Fallis, Gerstein, Giacomini,
Greenberg, Hafler, Ionete, Kaunzner, Kodama, Lock, Longbrake, Musch, Pardo, Piehl,
Weber, Yuen, Ziemssen, Bose, Freedman, Anania, Ramesh, Winger, Jia, Herman, Harp,
Bar-Or.
Statistical analysis: Thebault, Cameron, Kodama, Musch, Anania, Ramesh, Jia.
Obtained funding: Hafler, Winger, Herman, Bar-Or.
Administrative, technical, or material support: Bennett, Carruthers, Gerstein, Ionete, Kaunzner, Lock, Piehl, Yuen, Ziemssen, Freedman,
Anania, Jia, Herman, Bar-Or.
Supervision: Hafler, Lock, Pardo, Weber, Yuen, Ziemssen, Freedman, Anania, Winger, Jia, Herman,
Harp, Bar-Or.
Other: provided confirmatory cohort data and analyses: Thebault.
Conflict of Interest Disclosures: Dr Cross reported grants from Genentech for financial support of the multicenter
study and nonfinancial support from Genentech (help with statistical analysis) during
the conduct of the study; consulting, speaking, and/or advisory board fees from Biogen,
Bristol Myers Squibb, Janssen, Horizon, Novartis, Genentech, EMD Serono (Merck), TG
Therapeutics, and Octave outside the submitted work; and having a patent for 15060-630
(015875; “Methods for simultaneous multi-angular relaxometry of tissue using magnetic
resonance imaging”). Dr Gelfand reported grants from Hoffmann-LaRoche for research
support to his institution for clinical trials during the conduct of the study; grants
from Vigil Neurosciences for research support for clinical trials and personal fees
from Arialys Consulting outside the submitted work; and service on trial steering
committees for Hoffmann-LaRoche. Dr Bennett reported consulting, data monitoring board,
and/or speaking fees from Roche-Genentech, Alexion-AstraZeneca, Amgen, Imcyse, Mitsubishi-Tanabe,
Novartis, Beigene, Clene Nanomedicine, Antigenomycs, Reistone Bio, and TG Therapeutics
outside the submitted work. Dr von Büdingen reported being a shareholder of Roche.
Dr Cameron reported holding stock from Genentech/Roche outside the submitted work.
Dr Carruthers reported grants from Genentech and Roche Canada and personal fees from
Serono, Roche Canada, Biogen, Novartis, and Teva Canada during the conduct of the
study and personal fees from Alexion outside the submitted work. Dr Giacomini reported
grants, personal fees, and travel/educational grants from Roche during the conduct
of the study; personal fees from Biogen, BMS-Celgene, EMD Serono, Genzyme-Sanofi,
Novartis, Teva Innovation Canada, and Innodem Neurosciences and grants from the MS
Society of Canada outside the submitted work; and being the chief medical officer
of and having stock options in Innodem Neurosciences. Dr Greenberg reported grants
from Genentech during the conduct of the study; personal fees from Alexion, Novartis,
EMD Serono, Horizon, Genentech, Sandoz, Sanofi, Signant, TG Therapeutics, Cycle, Arialys,
Clene, Syneos, PRIME, and GenrAb; grants from Anokion and Regeneron; and nonfinancial
support from the Siegel Rare Neuroimmune Association outside the submitted work. Dr
Hafler reported grants from Genentech and Roche during the conduct of the study and
personal fees from Genentech, Sanofi, and GSK outside the submitted work. Dr Ionete
reported grants from Genentech during the conduct of the study; and being a scientific
advisor for Sanofi outside the submitted work. Dr Kaunzner reported clinical study
support from Genentech during the conduct of the study and grants from Genentech and
serving on advisory boards for Novartis and EMD Serono outside the submitted work.
Dr Lock reported personal fees from Bristol Myers Squibb, Horizon Therapeutics, Diagnose
Early, and InterX outside the submitted work. Dr Longbrake reported clinical trial
support from Genentech during the conduct of the study; personal fees from Genentech,
grants from Genentech and Biogen, and personal fees from Biogen, Janssen, TG Therapeutics,
NGM Bio, Bristol Myers Squibb, EMD Serono, and Genzyme outside the submitted work.
Dr Musch reported being a shareholder of Hoffmann-La Roche. Dr Pardo reported grants
from Roche Genentech during the conduct of the study; grants from Biogen Idec, Sanofi
Genzyme, Novartis Pharmaceuticals, EMD Serono, AbbVie, Bristol Myers Squibb, Celgene,
TG Therapeutics, and Roche Genentech; personal fees from Biogen Idec, Sanofi Genzyme,
Novartis Pharmaceuticals, EMD Serono, Bristol Myers Squibb, TG Therapeutics, Roche
Genentech, and Janssen outside the submitted work; and having Progentec Diagnostics
stock options. Dr Piehl reported clinical trial fees from Genentech during the conduct
of the study; research support and/or grants from Merck, Janssen, UCB, and Swedish
MRC; expert testimony fees from Novartis; and data monitoring committee fees from
Roche and Lundbeck outside the submitted work. Dr Yuen reported being a shareholder
of Hoffmann-La Roche. Dr Ziemssen reported grants and personal fees from Roche during
the conduct of the study and grants, personal fees, and/or nonfinancial support from
Sanofi, Teva, Novartis, Roche, Biogen, Sanofi, Bristol Myers Squibb, Almirall, and
Merck outside the submitted work. Dr Bose reported grants from the Multiple Sclerosis
Society of Canada, a TOHAMO innovation fund grant from IFPOC, and a Collaborate 2
Commercialize award from the Ontario Centre for Innovation and personal fees from
Teva Pharmaceuticals, EMD Serono, Novartis, and Sanofi Genzyme outside the submitted
work. Dr Freedman reported personal fees from Roche during the conduct of the study
and personal fees from Sanofi-Genzyme, Alexion/AstraZeneca, Biogen Idec, Atara Biotherapeutics,
EMD Serono/Merck Serono, Find Therapeutics, BMS/Celgene, Novartis, Setpoint Medical,
Sandoz, and Teva Canada Innovation outside the submitted work. Dr Winger reported
being a shareholder of Hoffmann-La Roche. Dr Herman reported being a shareholder in
Hoffmann-La Roche outside the submitted work. Dr Harp reported being a stockholder
of Genentech during the conduct of the study. Dr Bar-Or reported personal fees from
Abata, Novartis, and Roche/Genentech and grants from Biogen, Novartis, and Roche/Genentech
outside the submitted work. No other disclosures were reported.
Funding/Support: The test-cohort dataset was generated from a study funded by Genentech. The confirmatory
dataset was supported by the University of Ottawa multiple sclerosis program.
Role of the Funder/Sponsor: Genentech contributed to the design and conduct of the study and interpretation of
the data for the test cohort; otherwise, the supporting organizations had no role
in the collection, management, and analysis of the data; preparation, review, or approval
of the manuscript; and decision to submit the manuscript for publication.
Additional Contributions: We thank Christine Gould, PhD, CMPP, of Nucleus Global, for providing formatting
assistance, which was funded by Genentech in accordance with Good Publication Practice
guidelines. We also thank Shweta Kotwal, MS, MBBS; Aaron Schroeder, BS; Katie Dalpozzo,
BS; Jenny Jiang, MA; Yun-An Shen, MS; Damian Fiore, PharmD; David Spiciarich, PhD;
Ellen Casavant, PhD; and Manuel Magana, BA, for their operational and technical support;
Shristi Pandey, PhD (all Genentech, South San Francisco, at the time of their contributions),
for their bioinformatics support; and the patients who contributed samples and clinical
data.
Additional Information: Coauthor Keith Edwards, MD, died October 22, 2022.
