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

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.