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

Alyssa A. Toorop; Samantha Noteboom; Martijn D. Steenwijk; Job W. Gravendeel; Bas Jasperse; Frederik Barkhof; Eva M. M. Strijbis; Theo Rispens; Menno M. Schoonheim; Zoé L. E. van Kempen; Joep Killestein

doi:https://doi.org/10.1177/13524585231225855

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

Alyssa A. Toorop, Samantha Noteboom, Martijn D. Steenwijk, Job W. Gravendeel, Bas Jasperse, Frederik Barkhof, Eva M. M. Strijbis, Theo Rispens, Menno M. Schoonheim, Zoé L. E. van Kempen, Joep Killestein

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

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.

Original language	English
Pages (from-to)	266-271
Number of pages	6
Journal	MULTIPLE SCLEROSIS JOURNAL
Volume	30
Issue number	2
Early online date	2024
DOIs	https://doi.org/10.1177/13524585231225855
Publication status	Published - Feb 2024

Keywords

Multiple sclerosis
brain atrophy
drug concentration
extended interval dosing
natalizumab

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Toorop, A. A., Noteboom, S., Steenwijk, M. D., Gravendeel, J. W., Jasperse, B., Barkhof, F., Strijbis, E. M. M., Rispens, T., Schoonheim, M. M., van Kempen, Z. L. E., & Killestein, J. (2024). Exploring the effects of extended interval dosing of natalizumab and drug concentrations on brain atrophy in multiple sclerosis. MULTIPLE SCLEROSIS JOURNAL, 30(2), 266-271. https://doi.org/10.1177/13524585231225855

@article{850c3fe88c93426e94ac9dc814b72c61,

title = "Exploring the effects of extended interval dosing of natalizumab and drug concentrations on brain atrophy in multiple sclerosis",

abstract = "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.",

keywords = "Multiple sclerosis, brain atrophy, drug concentration, extended interval dosing, natalizumab",

author = "Toorop, {Alyssa A.} and Samantha Noteboom and Steenwijk, {Martijn D.} and Gravendeel, {Job W.} and Bas Jasperse and Frederik Barkhof and Strijbis, {Eva M. M.} and Theo Rispens and Schoonheim, {Menno M.} and {van Kempen}, {Zo{\'e} L. E.} and Joep Killestein",

note = "Publisher Copyright: {\textcopyright} The Author(s), 2024.",

year = "2024",

month = feb,

doi = "https://doi.org/10.1177/13524585231225855",

language = "English",

volume = "30",

pages = "266--271",

journal = "MULTIPLE SCLEROSIS JOURNAL",

issn = "1352-4585",

publisher = "SAGE Publications Ltd",

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}

Toorop, AA, Noteboom, S, Steenwijk, MD, Gravendeel, JW, Jasperse, B , Barkhof, F , Strijbis, EMM , Rispens, T , Schoonheim, MM , van Kempen, ZLE & Killestein, J 2024, 'Exploring the effects of extended interval dosing of natalizumab and drug concentrations on brain atrophy in multiple sclerosis', MULTIPLE SCLEROSIS JOURNAL, vol. 30, no. 2, pp. 266-271. https://doi.org/10.1177/13524585231225855

TY - JOUR

T1 - Exploring the effects of extended interval dosing of natalizumab and drug concentrations on brain atrophy in multiple sclerosis

AU - Toorop, Alyssa A.

AU - Noteboom, Samantha

AU - Steenwijk, Martijn D.

AU - Gravendeel, Job W.

AU - Jasperse, Bas

AU - Barkhof, Frederik

AU - Strijbis, Eva M. M.

AU - Rispens, Theo

AU - Schoonheim, Menno M.

AU - van Kempen, Zoé L. E.

AU - Killestein, Joep

N1 - Publisher Copyright: © The Author(s), 2024.

PY - 2024/2

Y1 - 2024/2

N2 - 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.

AB - 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.

KW - Multiple sclerosis

KW - brain atrophy

KW - drug concentration

KW - extended interval dosing

KW - natalizumab

UR - http://www.scopus.com/inward/record.url?scp=85182812239&partnerID=8YFLogxK

U2 - https://doi.org/10.1177/13524585231225855

DO - https://doi.org/10.1177/13524585231225855

M3 - Article

C2 - 38235514

SN - 1352-4585

VL - 30

SP - 266

EP - 271

JO - MULTIPLE SCLEROSIS JOURNAL

JF - MULTIPLE SCLEROSIS JOURNAL

IS - 2

ER -

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

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