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Article History

Received: 16 December 2025

Accepted: 11 February 2026

First Online: 6 March 2026

Declarations

:

: Enrique Alvarez has received compensation for advisory boards, lectures, and consultancy with Biogen, Celgene/BMS, Cionic, EMD Serono/Merck, Genentech/Roche, Genzyme, Horizon/Amgen, Novartis, Sanofi, and TG Therapeutics, and research support from Biogen, Genentech/Roche, Novartis, TG Therapeutics, Patient-Centered Outcomes Research Institute, National Multiple Sclerosis Society, National Institutes of Health, and Rocky Mountain MS Center. Hans-Peter Hartung has received honoraria for serving on steering and data monitoring committees, consulting, and speaking at symposia from Aurinia Pharma, Bayer Pharma AG, Biogen Idec, BMS Celgene, Merck KG Darmstadt, Neuraxpharm, Novartis, Roche, Sanofi, and TG Therapeutics, with approval by the rector of Heinrich-Heine University. Hans-Peter Hartung is an Editorial Board member of Neurology and Therapy . Hans-Peter Hartung was not involved in the selection of peer reviewers nor any of the subsequent editorial decisions. Lawrence Steinman has received research support and honoraria from BMS, Roche, and TG Therapeutics. Dr. Steinman serves on the Board of BioAtla and Pasithea Therapeutics. Derrick Robertson has received grant support from Anokion, Atara Biotherapeutics, Biogen, CorEvitas, EMD Serono, Genentech, GW Pharmaceuticals, Janssen, Novartis, PCORI, PRIME CME, Sanofi, TG Therapeutics, and UCB; has received consulting fees from Alexion, Amgen, Biogen, Bristol Myers Squibb, EMD Serono, Genentech, Greenwich Biosciences, Horizon, ImmPACT Bio, Janssen, Mallinckrodt, Novartis, Sanofi, and TG Therapeutics; has received honoraria or speaker fees from Alexion, Amgen, Biogen, Bristol Myers Squibb, EMD Serono, Genentech, Horizon, Janssen, PRIME CME, Sanofi, and TG Therapeutics. Peiqing Qian has received speaking and consulting honoraria from Biogen, BMS, Genzyme, Genentech, Viela Bio, and TG Therapeutics. Sibyl Wray has received compensation for serving on a scientific advisory or data safety monitoring board for Biogen, Bristol Myers Squibb/Celgene, EMD Serono, Novartis, Roche/Genentech, and Sanofi/Genzyme, and has received compensation for serving on a speaker’s bureau for Biogen, Bristol Myers Squibb, EMD Serono, Roche/Genentech, and Sanofi/Genzyme. The institution of Dr. Wray has received research support from Amgen, Biogen, Bristol Myers Squibb/Celgene, Contineum, Novartis, Roche/Genentech, Sanofi/Genzyme, and TG Therapeutics. Douglas L. Arnold has received consulting fees from Biogen, Celgene, Eli Lilly, EMD Serono, Frequency Therapeutics, Merck, Novartis, Roche, Sanofi, and Xfacto and holds stock in NeuroRx. Edward Fox, Yihuan Xu, Koby Mok, Anne Gocke, and Christopher Garner are all employees of TG Therapeutics, Inc. Bruce Cree is a consultant for Alexion, Alumis, Avotres, Biogen, Boston Pharma, EMD Serono, Hexal/Sandoz, Horizon, Immunic AG, Kyverna, Neuron23, Novartis, Sanofi, Siemens, and TG Therapeutics, received research support from Genentech and Kyverna, and is on an advisory board for Autobahn.

: Each study site's institutional review board or ethics committee approved the trials (US central IRB approval reference numbers ULTIMATE I Pro00021474, ULTIMATE II Pro00021820), which adhered to Good Clinical Practice guidelines and the principles of the Declaration of Helsinki. Written informed consent was obtained from all participants.