Ocrelizumab in relapsing and primary progressive multiple sclerosis: Pharmacokinetic and pharmacodynamic analyses of OPERA I, OPERA II and ORATORIO.

British Journal of Clinical Pharmacology
Ekaterina GibianskyHeidemarie Kletzl

Abstract

Ocrelizumab is a humanized monoclonal antibody that selectively targets CD20-positive B cells and is indicated for treatment of patients with relapsing forms of multiple sclerosis (RMS) or primary progressive multiple sclerosis (PPMS). The pharmacokinetics and pharmacodynamics of ocrelizumab in patients with RMS or PPMS were assessed. A population pharmacokinetic model was developed based on data from the Phase II study and the Phase III studies OPERA I and OPERA II in patients with RMS. Data from the ORATORIO Phase III study in patients with PPMS became available after model finalization and was used for external model evaluation. The ocrelizumab serum concentration vs time course was accurately described by a 2-compartment model with time-dependent clearance. Body weight was found to be the main covariate. The area under the concentration-time curve over the dosing interval was estimated to be 26% higher for patients with RMS weighing <60 kg and 21% lower for patients weighing >90 kg when compared with the 60-90 kg group. The terminal half-life of ocrelizumab was estimated as 26 days. The extent of B-cell depletion in blood, as the pharmacodynamic marker, was greater with increasing ocrelizumab exposure. The pharmacokinetics ...Continue Reading

References

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Citations

Mar 31, 2021·Current Opinion in Neurology·Finn Sellebjerg, Martin S Weber
Aug 7, 2021·Therapeutics and Clinical Risk Management·Chiara Rosa MancinelliRuggero Capra
Aug 8, 2021·International Journal of Environmental Research and Public Health·Gianmarco AbbadessaSimona Bonavita
Oct 9, 2021·Multiple Sclerosis : Clinical and Laboratory Research·Michael ZhongVilija G Jokubaitis

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Software Mentioned

Intel Visual Fortran Professional Compiler
R
NONMEM
ORATORIO
Windows 7 Professional

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