Individual Variability of CD19+ B-Cell Repopulation in People With Multiple Sclerosis Treated With Extended Interval Dosing of Ocrelizumab

Laura Hogenboom; Lisa G Schoof; Liza M Y Gelissen; Jop Mostert; Luuk van Rooij; Elske Hoitsma; Caspar E P van Munster; Jeroen van Eijk; Nienke F Kalkers; Kirsten S Adriani; Anke Vennegoor; Ilse M P Arts; Liselore Mensing; Marijke Eurelings; Koen de Gans; Oliver Gerlach; Erwin L J Hoogervorst; Mark E Kloosterziel; Jolijn J Kragt; Ruben P Portier; Ide Smets; Björn M van Geel; Jessica Nielsen; Christiaan M Roosendaal; Jurgen R Piet; Esther Zeinstra; Onno N Groeneveld; Bob W van Oosten; Brigit A de Jong; Bernard M J Uitdehaag; Eva M M Strijbis; Birgit I Lissenberg-Witte; Joep Killestein; Zoé L E van Kempen

doi:10.1111/ene.70695

Individual Variability of CD19+ B-Cell Repopulation in People With Multiple Sclerosis Treated With Extended Interval Dosing of Ocrelizumab

Laura Hogenboom^*
, Lisa G Schoof
, Liza M Y Gelissen
, Jop Mostert
, Luuk van Rooij
, Elske Hoitsma
, Caspar E P van Munster
, Jeroen van Eijk
, Nienke F Kalkers
, Kirsten S Adriani
, Anke Vennegoor
, Ilse M P Arts
, Liselore Mensing
, Marijke Eurelings
, Koen de Gans
, Oliver Gerlach
, Erwin L J Hoogervorst
, Mark E Kloosterziel
, Jolijn J Kragt
, Ruben P Portier

Ide Smets, Björn M van Geel, Jessica Nielsen, Christiaan M Roosendaal, Jurgen R Piet, Esther Zeinstra, Onno N Groeneveld, Bob W van Oosten, Brigit A de Jong, Bernard M J Uitdehaag, Eva M M Strijbis, Birgit I Lissenberg-Witte, Joep Killestein, Zoé L E van Kempen

^*Corresponding author for this work

Julius Center, dept. Data Science & Biostatistics

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

1 Downloads (Pure)

Abstract

BACKGROUND AND OBJECTIVES: B-cell repopulation patterns in ocrelizumab treated patients with multiple sclerosis are highly variable between individuals, but the course of B-cell reoccurrence after subsequent doses within an individual is not yet determined. Our aim was to determine the intraindividual variability of CD19+ B-cell repopulation after each ocrelizumab dose when using CD19+ B-cell guided interval dosing.

METHODS: This was a prospective cohort study, as part of the ongoing BLOOMS trial, investigating participants randomised for B-cell guided interval dosing of ocrelizumab with ≥ 2 dosing intervals. Coefficients of variation were calculated for time from last ocrelizumab dose to first CD19+ B-cell measurement ≥ 0.01 × 109 cells/L.

RESULTS: Seventy-five participants with a total of 209 B-cell guided intervals were included. Time from last dose to first appearance of CD19+ B-cell count ≥ 0.01 × 109 cells/L showed wide variability between individuals (20.6-72.1 weeks), but the median variation was 5.6% (IQR: 3.1-8.4) within an individual. This translated to a variation of 2 weeks per dosing interval on average.

DISCUSSION: Time to CD19+ B-cell repopulation after each ocrelizumab dose is individually stable. This finding could pave the way for easier and more accessible future personalised interval dosing of B-cell depleting therapies if this stability is confirmed in long-term treatment.

Original language	English
Article number	e70695
Journal	European Journal of Neurology
Volume	33
Issue number	7
DOIs	https://doi.org/10.1111/ene.70695
Publication status	Published - Jul 2026

Keywords

Humans
B-Lymphocytes/drug effects
Female
Antibodies, Monoclonal, Humanized/administration & dosage
Antigens, CD19/metabolism
Male
Multiple Sclerosis/drug therapy
Adult
Immunologic Factors/administration & dosage
Middle Aged
Prospective Studies

Access to Document

10.1111/ene.70695Licence: CC BY

Euro J of Neurology - 2026 - Hogenboom - Individual Variability of CD19 B‐Cell Repopulation in People With MultipleFinal published version, 618 KBLicence: CC BY

Cite this

Hogenboom, L., Schoof, L. G., Gelissen, L. M. Y., Mostert, J., van Rooij, L., Hoitsma, E., van Munster, C. E. P., van Eijk, J., Kalkers, N. F., Adriani, K. S., Vennegoor, A., Arts, I. M. P., Mensing, L., Eurelings, M., de Gans, K., Gerlach, O., Hoogervorst, E. L. J., Kloosterziel, M. E., Kragt, J. J., ... van Kempen, Z. L. E. (2026). Individual Variability of CD19+ B-Cell Repopulation in People With Multiple Sclerosis Treated With Extended Interval Dosing of Ocrelizumab. European Journal of Neurology, 33(7), Article e70695. https://doi.org/10.1111/ene.70695

@article{16186631ac22470f8db5c402c7abfa2f,

title = "Individual Variability of CD19+ B-Cell Repopulation in People With Multiple Sclerosis Treated With Extended Interval Dosing of Ocrelizumab",

abstract = "BACKGROUND AND OBJECTIVES: B-cell repopulation patterns in ocrelizumab treated patients with multiple sclerosis are highly variable between individuals, but the course of B-cell reoccurrence after subsequent doses within an individual is not yet determined. Our aim was to determine the intraindividual variability of CD19+ B-cell repopulation after each ocrelizumab dose when using CD19+ B-cell guided interval dosing.METHODS: This was a prospective cohort study, as part of the ongoing BLOOMS trial, investigating participants randomised for B-cell guided interval dosing of ocrelizumab with ≥ 2 dosing intervals. Coefficients of variation were calculated for time from last ocrelizumab dose to first CD19+ B-cell measurement ≥ 0.01 × 109 cells/L.RESULTS: Seventy-five participants with a total of 209 B-cell guided intervals were included. Time from last dose to first appearance of CD19+ B-cell count ≥ 0.01 × 109 cells/L showed wide variability between individuals (20.6-72.1 weeks), but the median variation was 5.6\% (IQR: 3.1-8.4) within an individual. This translated to a variation of 2 weeks per dosing interval on average.DISCUSSION: Time to CD19+ B-cell repopulation after each ocrelizumab dose is individually stable. This finding could pave the way for easier and more accessible future personalised interval dosing of B-cell depleting therapies if this stability is confirmed in long-term treatment.",

keywords = "Humans, B-Lymphocytes/drug effects, Female, Antibodies, Monoclonal, Humanized/administration \& dosage, Antigens, CD19/metabolism, Male, Multiple Sclerosis/drug therapy, Adult, Immunologic Factors/administration \& dosage, Middle Aged, Prospective Studies",

author = "Laura Hogenboom and Schoof, \{Lisa G\} and Gelissen, \{Liza M Y\} and Jop Mostert and \{van Rooij\}, Luuk and Elske Hoitsma and \{van Munster\}, \{Caspar E P\} and \{van Eijk\}, Jeroen and Kalkers, \{Nienke F\} and Adriani, \{Kirsten S\} and Anke Vennegoor and Arts, \{Ilse M P\} and Liselore Mensing and Marijke Eurelings and \{de Gans\}, Koen and Oliver Gerlach and Hoogervorst, \{Erwin L J\} and Kloosterziel, \{Mark E\} and Kragt, \{Jolijn J\} and Portier, \{Ruben P\} and Ide Smets and \{van Geel\}, \{Bj{\"o}rn M\} and Jessica Nielsen and Roosendaal, \{Christiaan M\} and Piet, \{Jurgen R\} and Esther Zeinstra and Groeneveld, \{Onno N\} and \{van Oosten\}, \{Bob W\} and \{de Jong\}, \{Brigit A\} and Uitdehaag, \{Bernard M J\} and Strijbis, \{Eva M M\} and Lissenberg-Witte, \{Birgit I\} and Joep Killestein and \{van Kempen\}, \{Zo{\'e} L E\}",

note = "{\textcopyright} 2026 The Author(s). European Journal of Neurology published by John Wiley \& Sons Ltd on behalf of European Academy of Neurology.",

year = "2026",

month = jul,

doi = "10.1111/ene.70695",

language = "English",

volume = "33",

journal = "European Journal of Neurology",

issn = "1351-5101",

publisher = "Wiley-Blackwell Publishing Ltd",

number = "7",

}

Hogenboom, L, Schoof, LG, Gelissen, LMY, Mostert, J, van Rooij, L, Hoitsma, E, van Munster, CEP, van Eijk, J, Kalkers, NF, Adriani, KS, Vennegoor, A, Arts, IMP, Mensing, L, Eurelings, M, de Gans, K, Gerlach, O, Hoogervorst, ELJ, Kloosterziel, ME, Kragt, JJ, Portier, RP, Smets, I, van Geel, BM, Nielsen, J, Roosendaal, CM, Piet, JR, Zeinstra, E, Groeneveld, ON, van Oosten, BW, de Jong, BA, Uitdehaag, BMJ, Strijbis, EMM, Lissenberg-Witte, BI, Killestein, J & van Kempen, ZLE 2026, 'Individual Variability of CD19+ B-Cell Repopulation in People With Multiple Sclerosis Treated With Extended Interval Dosing of Ocrelizumab', European Journal of Neurology, vol. 33, no. 7, e70695. https://doi.org/10.1111/ene.70695

TY - JOUR

T1 - Individual Variability of CD19+ B-Cell Repopulation in People With Multiple Sclerosis Treated With Extended Interval Dosing of Ocrelizumab

AU - Hogenboom, Laura

AU - Schoof, Lisa G

AU - Gelissen, Liza M Y

AU - Mostert, Jop

AU - van Rooij, Luuk

AU - Hoitsma, Elske

AU - van Munster, Caspar E P

AU - van Eijk, Jeroen

AU - Kalkers, Nienke F

AU - Adriani, Kirsten S

AU - Vennegoor, Anke

AU - Arts, Ilse M P

AU - Mensing, Liselore

AU - Eurelings, Marijke

AU - de Gans, Koen

AU - Gerlach, Oliver

AU - Hoogervorst, Erwin L J

AU - Kloosterziel, Mark E

AU - Kragt, Jolijn J

AU - Portier, Ruben P

AU - Smets, Ide

AU - van Geel, Björn M

AU - Nielsen, Jessica

AU - Roosendaal, Christiaan M

AU - Piet, Jurgen R

AU - Zeinstra, Esther

AU - Groeneveld, Onno N

AU - van Oosten, Bob W

AU - de Jong, Brigit A

AU - Uitdehaag, Bernard M J

AU - Strijbis, Eva M M

AU - Lissenberg-Witte, Birgit I

AU - Killestein, Joep

AU - van Kempen, Zoé L E

PY - 2026/7

Y1 - 2026/7

N2 - BACKGROUND AND OBJECTIVES: B-cell repopulation patterns in ocrelizumab treated patients with multiple sclerosis are highly variable between individuals, but the course of B-cell reoccurrence after subsequent doses within an individual is not yet determined. Our aim was to determine the intraindividual variability of CD19+ B-cell repopulation after each ocrelizumab dose when using CD19+ B-cell guided interval dosing.METHODS: This was a prospective cohort study, as part of the ongoing BLOOMS trial, investigating participants randomised for B-cell guided interval dosing of ocrelizumab with ≥ 2 dosing intervals. Coefficients of variation were calculated for time from last ocrelizumab dose to first CD19+ B-cell measurement ≥ 0.01 × 109 cells/L.RESULTS: Seventy-five participants with a total of 209 B-cell guided intervals were included. Time from last dose to first appearance of CD19+ B-cell count ≥ 0.01 × 109 cells/L showed wide variability between individuals (20.6-72.1 weeks), but the median variation was 5.6% (IQR: 3.1-8.4) within an individual. This translated to a variation of 2 weeks per dosing interval on average.DISCUSSION: Time to CD19+ B-cell repopulation after each ocrelizumab dose is individually stable. This finding could pave the way for easier and more accessible future personalised interval dosing of B-cell depleting therapies if this stability is confirmed in long-term treatment.

AB - BACKGROUND AND OBJECTIVES: B-cell repopulation patterns in ocrelizumab treated patients with multiple sclerosis are highly variable between individuals, but the course of B-cell reoccurrence after subsequent doses within an individual is not yet determined. Our aim was to determine the intraindividual variability of CD19+ B-cell repopulation after each ocrelizumab dose when using CD19+ B-cell guided interval dosing.METHODS: This was a prospective cohort study, as part of the ongoing BLOOMS trial, investigating participants randomised for B-cell guided interval dosing of ocrelizumab with ≥ 2 dosing intervals. Coefficients of variation were calculated for time from last ocrelizumab dose to first CD19+ B-cell measurement ≥ 0.01 × 109 cells/L.RESULTS: Seventy-five participants with a total of 209 B-cell guided intervals were included. Time from last dose to first appearance of CD19+ B-cell count ≥ 0.01 × 109 cells/L showed wide variability between individuals (20.6-72.1 weeks), but the median variation was 5.6% (IQR: 3.1-8.4) within an individual. This translated to a variation of 2 weeks per dosing interval on average.DISCUSSION: Time to CD19+ B-cell repopulation after each ocrelizumab dose is individually stable. This finding could pave the way for easier and more accessible future personalised interval dosing of B-cell depleting therapies if this stability is confirmed in long-term treatment.

KW - Humans

KW - B-Lymphocytes/drug effects

KW - Female

KW - Antibodies, Monoclonal, Humanized/administration & dosage

KW - Antigens, CD19/metabolism

KW - Male

KW - Multiple Sclerosis/drug therapy

KW - Adult

KW - Immunologic Factors/administration & dosage

KW - Middle Aged

KW - Prospective Studies

U2 - 10.1111/ene.70695

DO - 10.1111/ene.70695

M3 - Article

C2 - 42411923

SN - 1351-5101

VL - 33

JO - European Journal of Neurology

JF - European Journal of Neurology

IS - 7

M1 - e70695

ER -

Individual Variability of CD19+ B-Cell Repopulation in People With Multiple Sclerosis Treated With Extended Interval Dosing of Ocrelizumab

Abstract

Keywords

Access to Document

Fingerprint

Cite this