Exploring the effects of extended interval dosing of natalizumab and drug concentrations on brain atrophy in multiple sclerosis.

Autor:	Toorop AA; MS Center Amsterdam, Department of Neurology, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam, The Netherlands., Noteboom S; MS Center Amsterdam, Department of Anatomy & Neurosciences, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam, The Netherlands., Steenwijk MD; MS Center Amsterdam, Department of Anatomy & Neurosciences, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam, The Netherlands., Gravendeel JW; MS Center Amsterdam, Department of Neurology, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam, The Netherlands., Jasperse B; MS Center Amsterdam, Department of Radiology and Nuclear Medicine, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam, The Netherlands., Barkhof F; MS Center Amsterdam, Department of Radiology and Nuclear Medicine, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam, The Netherlands.; Queen Square Institute of Neurology and Centre for Medical Image Computing, University College London, London, UK., Strijbis EM; MS Center Amsterdam, Department of Neurology, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam, The Netherlands., Rispens T; Biologics Laboratory and Department of Immunopathology, Sanquin Diagnostic Services, Amsterdam, The Netherlands.; Landsteiner Laboratory, Academic Medical Center, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands., Schoonheim MM; MS Center Amsterdam, Department of Anatomy & Neurosciences, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam, The Netherlands., van Kempen ZL; MS Center Amsterdam, Department of Neurology, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam, The Netherlands., Killestein J; MS Center Amsterdam, Department of Neurology, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam, The Netherlands.
Jazyk:	angličtina
Zdroj:	Multiple sclerosis (Houndmills, Basingstoke, England) [Mult Scler] 2024 Feb; Vol. 30 (2), pp. 266-271. Date of Electronic Publication: 2024 Jan 18.
DOI:	10.1177/13524585231225855
Abstrakt:	Background: Extended interval dosing (EID) of natalizumab treatment is increasingly used in multiple sclerosis. Besides the clear anti-inflammatory effect, natalizumab is considered to have neuroprotective properties as well. Objectives: This study aimed to study the longitudinal effects of EID compared to standard interval dosing (SID) and natalizumab drug concentrations on brain atrophy. Methods: Patients receiving EID or SID of natalizumab with a minimum radiological follow-up of 2 years were included. Changes in brain atrophy measures over time were derived from clinical routine 3D-Fluid Attenuated Inversion Recovery (FLAIR)-weighted magnetic resonance imaging (MRI) scans using SynthSeg. Results: We found no differences between EID ( n = 32) and SID ( n = 50) for whole brain (-0.21% vs -0.16%, p = 0.42), ventricular (1.84% vs 1.13%, p = 0.24), and thalamic (-0.32% vs -0.32%, p = 0.97) annualized volume change over a median follow-up of 3.2 years. No associations between natalizumab drug concentration and brain atrophy rate were found. Conclusion: We found no clear evidence that EID compared to SID or lower natalizumab drug concentrations have a negative impact on the development of brain atrophy over time. Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: A.A.T. has nothing to disclose. S.N. is supported by research grants from Atara Biotherapeutics, Merck, and Biogen. M.D.S. has received funding from Atara Biotherapeutics, Merck, MedDay, and Biogen. J.W.G. has nothing to disclose. B.J. has nothing to disclose. F.B. is supported by the NIHR Biomedical Research Centre at UCLH; steering committee or Data Safety Monitoring Board member for Biogen, Merck, ATRI/ACTC, and Prothena; consultant for Roche, Celltrion, Rewind Therapeutics, Merck, IXICO, Jansen, and Combinostics; research agreements with Merck, Biogen, GE HealthCare, and Roche; co-founder and shareholder of Queen Square Analytics Ltd. E.M.M.S. has nothing to disclose. M.M.S. serves on the editorial board of Neurology and Frontiers in Neurology, receives research support from the Dutch MS Research Foundation, Eurostars-EUREKA, ARSEP, Amsterdam Neuroscience, MAGNIMS and ZonMW (Vidi grant, project no. 09150172010056) and has served as a consultant for or received research support from Atara Biotherapeutics, Biogen, Celgene/Bristol Myers Squibb, EIP, Sanofi, MedDay, and Merck. T.R. received funding for research from Genmab and consultancy fees from Novartis. Z.L.E.v.K. has nothing to disclose. J.K. received research grants for multicenter investigator-initiated trials DOT-MS trial, ClinicalTrials.gov Identifier: NCT04260711 (ZonMW) and BLOOMS trial (ZonMW and Treatmeds), ClinicalTrials.gov Identifier: NCT05296161; received consulting fees for F. Hoffmann-La Roche Ltd, Biogen, Teva, Merck, Novartis, and Sanofi/Genzyme (all payments to institution); reports speaker relationships with F. Hoffmann-La Roche Ltd, Biogen, Immunic, Teva, Merck, Novartis, and Sanofi/Genzyme (all payments to institution); adjudication committee of MS clinical trial of Immunic (payments to institution only).
Databáze:	MEDLINE
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