PhD defence W.J.R. (Willem) Fokkink

Below is a brief summary of the dissertation: 

Intravenous immunoglobulin (IVIg) is the cornerstone of treatment for the Guillain-Barré syndrome (GBS) and chronic inflammatory demyelinating polyneuropathy (CIDP). Both result in damage to the peripheral nerves and nerve roots, causing paresis and sensory deficits that can result in severe disability or sometimes death. The exact working mechanism for the proven therapeutic effect of IVIg in these two immune-mediated neuropathies remains unknown. We do know that a high-dose IVIg treatment is required for an anti-inflammatory effect. Dosing for both diseases is based on bodyweight, with subsequent maintenance dosing for CIDP varying greatly. Empiric guidelines or readily-available biomarkers to monitor these doses are currently lacking. Leaving patients at risk for both undertreatment and overtreatment with this expensive and scarce drug. For GBS the standard induction course seems insufficient for about 20-25% of the patients with poor outcome, despite timely treatment. We aimed to establish an understanding of the pharmacokinetics (PK) of IVIg and to find biomarkers that could influence or predict the PK of IVIg in patients with GBS or CIDP. We undertook a series of studies to get an understanding of the presumed important factors in immunoglobulin G (IgG) metabolism assessing: IgG glycosylation, genetic variation in relevant receptors, other proteins of potential influence and disease/demographic features. Data of 369 patients was analysed by means of non-linear mixed-effects modelling. This culminated in the first population-pharmacokinetic model of IVIg treatment in GBS, providing us with a new tool to predict the PK and thereby the pharmacodynamics of IVIg to start personalising treatment.