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

Abstract

Abstract 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.