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

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 (

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.

Déclaration de conflit d'intérêts

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).