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Original research
Ocrelizumab concentration and antidrug antibodies are associated with B-cell count in multiple sclerosis
  1. Alyssa A Toorop1,
  2. Laura Hogenboom1,
  3. Karien Bloem2,
  4. Merve Kocyigit1,
  5. Nadine W M Commandeur2,
  6. Anne Wijnants2,
  7. Birgit I Lissenberg-Witte3,
  8. Eva M M Strijbis1,
  9. Bernard M J Uitdehaag1,
  10. Theo Rispens2,4,
  11. Joep Killestein1,
  12. Zoé L E van Kempen1
  1. 1Department of Neurology, MS Center Amsterdam, Amsterdam UMC Location VUMC, Amsterdam, The Netherlands
  2. 2Biologics Laboratory, Sanquin Diagnostic Services, Amsterdam, The Netherlands
  3. 3Department of Epidemiology and Data Science, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
  4. 4Landsteiner Laboratory, Amsterdam UMC Location AMC, Amsterdam, The Netherlands
  1. Correspondence to Ms Alyssa A Toorop, Neurology, Amsterdam UMC Locatie VUmc, 1081 HV Amsterdam, Noord-Holland, The Netherlands; a.toorop{at}amsterdamumc.nl

Abstract

Background The majority of patients with multiple sclerosis on ocrelizumab have B-cell depletion after standard interval dosing of 26 weeks. With B-cell-guided dosing patients receive their next dose when B-cell repopulation occurs. Prediction of B-cell repopulation using ocrelizumab concentrations could aid in personalising treatment regimes. The objectives of this study were to evaluate the association between ocrelizumab drug concentration, antidrug antibodies (ADAs) and CD19 B-cell count, and to define a cut-off ocrelizumab concentration for start of B-cell repopulation (defined by ≥10 CD19+ B cells/µL).

Methods In this investigator-initiated prospective study, blood samples at various time points during ocrelizumab treatment were collected from a biobank. Serum ocrelizumab concentrations and ADAs were measured with two different assays developed for this study. Data were analysed using linear mixed effect models. An receiver operating characteristic (ROC) curve was used to determine a cut-off ocrelizumab concentration for start of B-cell repopulation (defined by ≥10 cells/µL).

Results A total of 452 blood samples from 72 patients were analysed. Ocrelizumab concentrations were detectable up until 53.3 weeks after last infusion and ranged between <0.0025 and 204 µg/mL after 1–67 weeks. Ocrelizumab concentration was negatively associated with B-cell count, with body mass index identified as effect modifier. We found a cut-off value of 0.06 µg/mL for start of B-cell repopulation of ≥10 cells/µL. Ocrelizumab ADAs were detectable in four patients (5.7%) with corresponding low ocrelizumab concentrations and start of B-cell repopulation.

Conclusions Serum ocrelizumab concentration was strongly associated with B-cell count. Measurement of ocrelizumab drug concentrations and ADAs could play an important role to further personalise treatment and predict the start of B-cell repopulation.

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Data availability statement

Data are available on reasonable request. Anonymised data will be shared on reasonable request with any qualified investigator.

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Data availability statement

Data are available on reasonable request. Anonymised data will be shared on reasonable request with any qualified investigator.

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Footnotes

  • Contributors AAT: designed and conceptualised study; major role in acquisition of data; analysed and interpreted the data; drafted and revised the manuscript for intellectual content; had full access to all the data in the study and takes responsibility as guarantor for the integrity of the data and the accuracy of the data analysis. LH: interpreted the data; revised the manuscript for intellectual content. KB: laboratory analyses; interpreted the data; revised the manuscript for intellectual content. MK: major role in acquisition of data; revised the manuscript for intellectual content. NWMC: laboratory analyses; interpreted the data; revised the manuscript for intellectual content. AW: laboratory analyses; interpreted the data; revised the manuscript for intellectual content. BIL-W: analysed and interpreted the data; revised the manuscript for intellectual content. EMS: interpreted the data; revised the manuscript for intellectual content. BMJU: interpreted the data; revised the manuscript for intellectual content. TR: laboratory analyses; analysed and interpreted the data; revised the manuscript for intellectual content. JK: designed and conceptualised study; interpreted the data; drafted and revised the manuscript for intellectual content. ZLEvK: designed and conceptualised study; interpreted the data; drafted and revised the manuscript for intellectual content.

  • Funding This study was kindly funded by the Dutch MS Research Foundation (21-1135).

  • Disclaimer The funding party had no further involvement in the study.

  • Competing interests AAT: nothing to disclose. LH: nothing to disclose. KB: nothing to disclose. MK: nothing to disclose. NWMC: nothing to disclose. AW: nothing to disclose. BIL-W: nothing to disclose. EMMS: nothing to disclose. BMJU: received research support and/or consultancy fees from Biogen Idec, Genzyme, Merck Serono, Novartis, Roche, Teva and Immunic Therapeutics. TR: received funding for research from Genmab; consultancy fees from Novartis. JK: received research grants for multicentre 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, Biogen, Teva, Merck, Novartis and Sanofi/Genzyme (all payments to institution); reports speaker relationships with F. Hoffmann-La Roche, Biogen, Immunic, Teva, Merck, Novartis and Sanofi/Genzyme (all payments to institution); adjudication committee of MS clinical trial of Immunic (payments to institution only). ZLEvK: nothing to disclose.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.