Article Information
Accepted for Publication: January 28, 2021.
Published Online: March 29, 2021. doi:10.1001/jamaneurol.2021.0405
Corresponding Author: Ludwig Kappos, MD, Research Center for Clinical Neuroimmunology and Neuroscience
Basel, Departments of Medicine, Clinical Research, Biomedicine and Biomedical Engineering,
University Hospital and University of Basel, Spitalstrasse 2, CH-4031 Basel, Switzerland
(
ludwig.kappos@
123456usb.ch
).
Open Access: This is an open access article distributed under the terms of the
CC-BY-NC-ND License. © 2021 Kappos L et al.
JAMA Neurology.
Author Contributions: Dr Kappos had full access to all the data in the study and takes responsibility for
the integrity of the data and the accuracy of the data analysis.
Concept and design: Kappos, Burcklen, Hennessy, Pozzilli, D'Ambrosio, Linscheid, Vaclavkova, Sprenger.
Acquisition, analysis, or interpretation of data: Kappos, Fox, Burcklen, Freedman, Havrdová, Hennessy, Hohlfeld, Lublin, Montalban,
Pozzilli, Scherz, Linscheid, Vaclavkova, Pirozek-Lawniczek, Kracker, Sprenger.
Drafting of the manuscript: Kappos, Burcklen, Hennessy, Pozzilli, Scherz, Linscheid, Vaclavkova, Pirozek-Lawniczek.
Critical revision of the manuscript for important intellectual content: Kappos, Fox, Burcklen, Freedman, Havrdová, Hennessy, Hohlfeld, Lublin, Montalban,
Pozzilli, Scherz, D'Ambrosio, Vaclavkova, Pirozek-Lawniczek, Kracker, Sprenger.
Statistical analysis: Burcklen, Hennessy, Scherz, Vaclavkova, Kracker.
Administrative, technical, or material support: Burcklen, Hennessy, D'Ambrosio, Pirozek-Lawniczek.
Supervision: Kappos, Burcklen, Hennessy, Pozzilli, Scherz, D'Ambrosio, Vaclavkova, Sprenger.
Conflict of Interest Disclosures: In the last 3 years, Dr Kappos’ institution (University Hospital Basel) received
steering committee, advisory board, consultancy fees, and/or support for educational
activities exclusively for research support at the Department from Actelion (step
2A), Allergan, Almirall, Baxalta, Bayer Healthcare, Biogen, Celgene/Receptos, CSL-Behring,
Desitin, Excemed, Eisai, Genzyme, Japan Tobacco, Merck, Minoryx, Novartis, Pfizer,
F. Hoffmann–La Roche Ltd, Roche, Sanofi Aventis, Santhera, and Teva and license fees
for Neurostatus-UHB products. The research of the MS Center in Basel has been supported
by grants from Bayer, Biogen, Novartis, the Swiss MS Society, the Swiss National Research
Foundation, Innosuisse, the European Union, and Roche Research Foundations. Drs Burcklen,
Hennessy, Linscheid, Pirozek-Lawniczek, Vaclavkova, and Kracker are employees of Actelion
Pharmaceuticals, a Janssen Pharmaceutical company of Johnson & Johnson. Dr Hennessy
holds stock in Johnson & Johnson, Novo Nordisk, Arena Pharmaceuticals, and Galapagos
and reported being a salaried employee of Actelion Pharmaceuticals Ltd during the
conduct of the study. Drs Burcklen, Vaclavkova, and Kracker hold stock in Johnson
& Johnson. Dr D'Ambrosio was an employee of Actelion Pharmaceuticals, a Janssen Pharmaceutical
company of Johnson & Johnson, during the conduct of the study. Dr Scherz is an employee
of Actelion Pharmaceuticals, a Janssen Pharmaceutical company of Johnson & Johnson,
and a former employee of Novartis Pharma AG; she also holds stock in Johnson & Johnson.
Dr Freedman reported having received personal fees from Bristol Myers Squibb/Celgene
during the conduct of the study; honoraria from Actelion, Atara Biotherapeutics, Bayer
Healthcare, Biogen Idec, Bristol Myers Squibb/Celgene, Chugai, Clene Nanomedicine,
EMD Canada, Genzyme, Hoffman La–Roche Ltd, MedDay, Merck Serono, Novartis, Sanofi-Aventis/Sanofi
Genzyme, and Teva Canada Innovation; and grants from Sanofi Genzyme and Roche outside
the submitted work. Dr Fox reports having received personal consulting fees from AB
Science, Actelion, Biogen, Celgene, EMD Serono, Genentech, Immunic, Novartis, Sanofi,
Teva, and TG Therapeutics; served on advisory committees for Actelion, Biogen, Immunic,
and Novartis; and received clinical trial contract and research grant funding from
Biogen and Novartis outside the submitted work. Dr Hohlfeld received honoraria from
Actelion, Biogen, Genzyme-Sanofi, Novartis, and Roche and research support from Biogen,
Genzyme-Sanofi, Novartis, and Roche. Dr Hohlfeld also reported personal fees from
Novartis, Sanofi, Merck, Biogen, Teva, Janssen/Johnson-Johnson, and Roche during the
conduct of the study. Dr Lublin has received honoraria from Biogen, EMD Serono, Novartis,
Teva, Actelion, Sanofi/Genzyme, Acorda, Roche/Genentech, MedImmune, Receptos/Celgene,
Forward Pharma, TG Therapeutics, Abbvie, Regeneron, Medday, Atara Biotherapeutics,
Polpharma, Mapi Pharma, Innate Immunotherapeutics, Apitope, Orion Biotechnology, Brainstorm
Cell Therapeutics, Jazz Pharmaceuticals, and GW Pharma. Dr Havrdová reported personal
fees, advisory board membership, and/or speaker's honoraria from Biogen, Novartis,
Roche, Sanofi, and Actelion and board membership for Celgene and Merck during the
conduct of the study, as well as advisory board membership and speaker's honoraria
from Biogen, Novartis, Roche, and Sanofi Genzyme; advisory board membership from Celgene
and Sandoz; speaker’s honoraria and membership in a clinical trial advisory board
membership from Merck Sernon; clinical trial advisory board membership with Actelion
outside the submitted work, plus honoraria or research support from Teva and Merck
Serono; and support from the Czech Ministry of Education (research project PROGRES
Q27/LF1). Dr Montalban has received speaking honoraria and travel expenses for participation
in scientific meetings and has been a steering committee member of clinical trials
or participated in advisory boards of clinical trials in the past years with Actelion,
Alexion, Bayer, Biogen, Celgene, EMD Serono, Genzyme, Immunic, Medday, Merck, Mylan,
Nervgen, Novartis, Roche, Sanofi-Genzyme, Teva Pharmaceutical, TG Therapeutics, Excemed,
Multiple Sclerosis International Federation, and National Multiple Sclerosis Society
outside the submitted work. Dr Sprenger’s institution has received honoraria for speaking
and consultation from Actelion, Biogen Idec, Desitin, Eli Lilly, Janssen, Johnson
& Johnson, Novartis, Roche, Sanofi Genzyme, Electrocore, Merck, and Teva. Dr Pozzilli
has served on scientific advisory boards for Novartis, Merck, Biogen, Sanofi, Genzyme,
Teva, and Actelion; received funding for travel and speaker honoraria from Biogen,
Teva, Sanofi Genzyme, Actelion, and Novartis; and received research support from Biogen,
Teva, Novartis, and Genzyme. Dr Lublin has received funding for research from Novartis,
Actelion, Biogen, Sanofi, National Multiple Sclerosis Society, the National Institutes
of Health, and Brainstorm Cell Therapeutics; has had consulting agreements or participated
in advisory boards or data safety monitoring boards for Biogen, EMD Serono, Novartis,
Teva, Actelion/Janssen, Sanofi/Genzyme, Acorda, Roche/Genentech, MedImmune/Viela Bio,
Receptos/Celgene, Bristol Myers Squibb, TG Therapeutics, Medday, Atara Biotherapeutics,
Polpharma, Mapi Pharma, Innate Immunotherapeutics, Apitope, Orion Biotechnology, Brainstorm
Cell Therapeutics, Jazz Pharmaceuticals, GW Pharma, Mylan, Immunic, Population Council,
and Avotres; and serving as a (nonpromotional) speaker for Sanofi, during which Dr
Lublin may discuss unapproved agents that are in the multiple sclerosis developmental
pipeline without any recommendation on their use. Finally, Dr Lublin reported consulting
fees from Actelion/Janssen during the conduct of the study and grants from Brainstorm
and stock options at Avotres outside the submitted work. No other disclosures were
reported.
Funding/Support: Funding was provided by Janssen Research & Development LLC, and the OPTIMUM study
was supported by Actelion Pharmaceuticals, part of Janssen Pharmaceutical Companies.
Role of the Funder/Sponsor: Janssen Research & Development LLC and Actelion Pharmaceuticals, part of Janssen
Pharmaceutical Companies, in collaboration with study investigators and the contracted
clinical research organizations, were responsible for the design and conduct of the
study; collection, management, analysis, and interpretation of the data; preparation,
review, or approval of the manuscript; and decision to submit the manuscript for publication.
Meeting Presentation: Parts of the results of this study were presented as abstracts at the American Academy
of Neurology Annual Meeting; April 25 to May 1, 2020; virtual; e-posters and e-presentations
at the Sixth Congress of the European Academy of Neurology; May 23 to 26, 2020; virtual;
and as an oral presentation at the European Committee for Treatment and Research in
Multiple Sclerosis; September 11 to 13, 2019; Stockholm, Sweden.
Additional Contributions: The authors thank the study participants without whom this study would not have been
accomplished. The authors thank Lisa Ford, MD, a paid employee of Janssen Research
& Development LLC, for her critical scientific and medical review and editorial contributions.
Writing assistance was provided by Anupama Singh, CMPP, and Shweta Pitre, CMPP, SIRO
Clinpharm Pvt Ltd, funded by Janssen Global Services. Additional editorial support
was provided by Bradford Challis, PhD, and Robert Achenbach, Janssen Global Services
LLC. These individuals were compensated.
Additional Information: See eAppendix 2, eTable 5, and eTable 6 in
Supplement 1 for details on the independent data monitoring committee, ophthalmology safety board,
major adverse cardiovascular event adjudication committee, MRI reading center, and
investigators. In addition, the data-sharing policy of Janssen Pharmaceutical Companies
of Johnson & Johnson is available at
https://www.janssen.com/clinical-trials/transparency. As noted on this site, requests for access to the study data can be submitted through
the Yale Open Data Access Project site at
https://yoda.yale.edu/.
