Ocrelizumab concentration and antidrug antibodies are associated with B-cell count in multiple sclerosis

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