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Population Pharmacokinetic Modelling of Intravenous Immunoglobulin Treatment in Patients with Guillain–Barré Syndrome

Authors :
Willem Jan R. Fokkink
Sander J. van Tilburg
Brenda C. M. de Winter
Sebastiaan D. T. Sassen
Pieter A. van Doorn
Birgit C. P. Koch
Bart C. Jacobs
Neurology
Immunology
Pharmacy
Source :
Clinical Pharmacokinetics, 61(9), 1285-1296. Adis
Publication Year :
2022

Abstract

Background and Objective: Intravenous immunoglobulin (IVIg) at a standard dosage is the treatment of choice for Guillain–Barré syndrome. The pharmacokinetics, however, is highly variable between patients, and a rapid clearance of IVIg is associated with poor recovery. We aimed to develop a model to predict the pharmacokinetics of a standard 5-day IVIg course (0.4 g/kg/day) in patients with Guillain–Barré syndrome. Methods: Non-linear mixed-effects modelling software (NONMEM®) was used to construct a pharmacokinetic model based on a model-building cohort of 177 patients with Guillain–Barré syndrome, with a total of 589 sequential serum samples tested for total immunoglobulin G (IgG) levels, and evaluated on an independent validation cohort that consisted of 177 patients with Guillain–Barré syndrome with 689 sequential serum samples. Results: The final two-compartment model accurately described the daily increment in serum IgG levels during a standard IVIg course; the initial rapid fall and then a gradual decline to steady-state levels thereafter. The covariates that increased IgG clearance were a more severe disease (as indicated by the Guillain–Barré syndrome disability score) and concomitant methylprednisolone treatment. When the current dosing regimen was simulated, the percentage of patients who reached a target ∆IgG > 7.3 g/L at 2 weeks decreased from 74% in mildly affected patients to only 33% in the most severely affected and mechanically ventilated patients (Guillain–Barré syndrome disability score of 5). Conclusions: This is the first population-pharmacokinetic model for standard IVIg treatment in Guillain–Barré syndrome. The model provides a new tool to predict the pharmacokinetics of alternative regimens of IVIg in Guillain–Barré syndrome to design future trials and personalise treatment.

Details

Language :
English
ISSN :
03125963
Volume :
61
Issue :
9
Database :
OpenAIRE
Journal :
Clinical Pharmacokinetics
Accession number :
edsair.doi.dedup.....be3a5750ded07869774ceeba084c5405