Switching disease-modifying therapies from sphingosine-1-phosphate receptor modulators to natalizumab or dimethyl fumarate restores immune responses after SARS-CoV-2 mRNA vaccination in patients with multiple sclerosis.

Autor: Kanakura M; Division of Health Sciences, Osaka University Graduate School of Medicine, Suita, Osaka, Japan., Kihara K; Department of Neurology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan., Kinoshita M; Department of Neurology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan. Electronic address: mkinoshita@neurol.med.osaka-u.ac.jp., Sugimoto T; Graduate School of Data Science, Shiga University, Hikone, Shiga, Japan., Murata H; Department of Neurology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan., Beppu S; Department of Neurology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan., Shiraishi N; Department of Neurology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan., Sugiyama Y; Department of Neurology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan., Koda T; Department of Neurology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan., Takahashi MP; Division of Health Sciences, Osaka University Graduate School of Medicine, Suita, Osaka, Japan., Chinen I; Biogen Japan, Tokyo, Japan., Okuno T; Department of Neurology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan. Electronic address: okuno@neurol.med.osaka-u.ac.jp., Mochizuki H; Department of Neurology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
Jazyk: angličtina
Zdroj: Clinical neurology and neurosurgery [Clin Neurol Neurosurg] 2024 Aug; Vol. 243, pp. 108378. Date of Electronic Publication: 2024 Jun 15.
DOI: 10.1016/j.clineuro.2024.108378
Abstrakt: Objectives: This study aimed to evaluate whether switching disease-modifying therapies (DMTs) from sphingosine-1 phosphate (S1P) receptor modulators to either natalizumab (NTZ) or dimethyl fumarate (DMF) could restore the effectiveness of SARS-CoV-2 mRNA vaccination in patients with multiple sclerosis (MS).
Methods: This study included 9 controls and 33 patients with MS: 7 patients treated with DMF, 7 patients treated with NTZ, 9 patients treated with S1P receptor modulators, and 10 patients who had switched DMTs from S1P receptor modulators to DMF or NTZ by the second vaccine dose. The patients who had switched DMTs were classified into two groups, based on whether their lymphocyte counts were above or below 1000/μL at the time of vaccination. In addition, relapses within 6 months after switching DMTs were also evaluated in these patients. Six months after the second dose of the vaccination, anti-SARS-CoV-2 spike antibodies were evaluated in all participants, and spike specific CD4 + T cells were also assessed in patients who had switched DMTs from S1P receptor modulators.
Results: Patients treated with S1P receptor modulators had lower levels of anti-SARS-CoV-2 spike antibodies than the controls and patients treated with DMF and NTZ. On the other hand, in patients who had switched DMTs from S1P receptor modulators, a recovery of lymphocyte counts above 1000/µL resulted in restored humoral and cellular immune responses to the vaccination. There were no neurological relapses in patients who had switched DMTs from S1P receptor modulators to NTZ.
Conclusion: SARS-CoV-2 mRNA vaccination is expected to be effective in patients whose lymphocyte counts have recovered due to switching DMTs from S1P receptor modulators. Switching DMTs from S1P receptor modulators to NTZ before vaccination may be beneficial in achieving efficacy for SARS-CoV-2 mRNA vaccination, with a reduced risk of relapse.
Competing Interests: Declaration of Competing Interest Tatsusada Okuno received research grants from Biogen and Mitsubishi Tanabe Pharma Corp. He has also received speaker fees from Biogen, Novartis and Mitsubishi Tanabe Pharma Corporation. Ichino Chinen is an employee of Biogen Japan and owns stocks of Biogen. Makoto Kinoshita has received speaker fees from Biogen and Novartis. Hisashi Murata has received payment for lectures from Alexion Pharmaceuticals Inc. and Mitsubishi Tanabe Pharma Corp. Hideki Mochizuki has received speaker fees from Biogen, Novartis and Mitsubishi Tanabe Pharma Corp.
(Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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