• Alyssa A Toorop, Laura Hogenboom, Karien Bloem, Merve Kocyigit, Nadine W M Commandeur, Anne Wijnants, Birgit I Lissenberg-Witte, Eva M M Strijbis, UitdehaagBernard M JBMJDepartment of Neurology, MS Center Amsterdam, Amsterdam UMC Location VUMC, Amsterdam, The Netherlands., Theo Rispens, Joep Killestein, and Zoé L E van Kempen.
• Department of Neurology, MS Center Amsterdam, Amsterdam UMC Location VUMC, Amsterdam, The Netherlands a.toorop@amsterdamumc.nl.
• J. Neurol. Neurosurg. Psychiatr. 2023 Jun 1; 94 (6): 487493487-493.

BackgroundThe 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).MethodsIn 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).ResultsA 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.ConclusionsSerum 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.© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.

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