Dose-exposure-efficacy response of intravenous immunoglobulin G 10% in multifocal motor neuropathy.

Autor: Li Z; Clinical Pharmacology & Early Clinical Development, Takeda Development Center Americas, Inc., Cambridge, Massachusetts, USA., Roepcke S; Pharmacometrics, Cognigen, a division of Simulations Plus, Buffalo, New York, USA., Franke R; Quantitative Clinical Pharmacology, Cognigen, a division of Simulations Plus, Buffalo, New York, USA., Yel L; Clinical Medicine, Takeda Development Center Americas, Inc., Cambridge, Massachusetts, USA.
Jazyk: angličtina
Zdroj: Annals of clinical and translational neurology [Ann Clin Transl Neurol] 2024 Aug; Vol. 11 (8), pp. 1977-1987. Date of Electronic Publication: 2024 Jul 08.
DOI: 10.1002/acn3.52098
Abstrakt: Objective: Multifocal motor neuropathy is a rare chronic immune-mediated neuropathy with impaired grip strength representing a common symptom. While intravenous immunoglobulin G is an effective treatment for the disease, significant variation in treatment response has been observed but not well understood. This analysis characterized dose-exposure-response relationships in multifocal motor neuropathy, using grip strength as a clinical efficacy measure.
Methods: Serum immunoglobulin G trough concentrations and grip strength data for the more affected hand from a Phase 3, randomized, double-blind, placebo-controlled, crossover trial of intravenous immunoglobulin 10% in 44 patients with multifocal motor neuropathy (NCT00666263) were used to develop a population pharmacokinetic-pharmacodynamic model.
Results: The model adequately described the observed pharmacokinetic and pharmacodynamic data and relationships between intravenous immunoglobulin 10% dose, serum immunoglobulin G trough levels, grip strength, and inter-patient variabilities in multifocal motor neuropathy. Model-based simulations for various dosing regimens (0.4-2.0 g/kg every 2-4 weeks) indicated that ≥1.6 g/kg/month would achieve clinically meaningful improvements in grip strength (≥4 kg) in ≥70% of patients. More frequent dosing at an equivalent monthly dose led to a more consistent response in grip strength. Furthermore, splitting the dose over multiple days for high doses (>1 g/kg) did not impact grip strength.
Interpretation: These findings suggest that the majority of patients with multifocal motor neuropathy would respond rapidly to intravenous immunoglobulin 10% with a range of dosing regimens. Shorter dosing intervals may avoid the diminishing response seen with longer dosing intervals. Dose-splitting provided similar outcomes while offering flexibility and convenience.
(© 2024 The Author(s). Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)
Databáze: MEDLINE
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