Immunoglobulin G dose-exposure-efficacy response in patients with chronic inflammatory demyelinating polyradiculoneuropathy.

INTRODUCTION

Intravenous immunoglobulin (IVIG) 10% and hyaluronidase-facilitated subcutaneous immunoglobulin (fSCIG) 10% are both used as maintenance treatments for patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Owing to the rarity of the condition, data regarding the relationship between dose, exposure, and clinical outcomes are sparse for these therapies. This analysis aimed to characterize the relationships between dose, exposure, and clinical efficacy of IVIG 10% and fSCIG 10% in CIDP.

MATERIALS AND

METHODS

Data were pooled from two phase 3 studies in patients with CIDP (NCT02549170; ADVANCE-CIDP 1) and multifocal motor neuropathy (NCT00666263). A sequential population pharmacokinetic (PK)-pharmacodynamic (PD) model was developed to characterize the PK-PD relationship between the PK of serum total immunoglobulin G (IgG) and, as the PD endpoint, the probability of increased adjusted Inflammatory Neuropathy Cause and Treatment (INCAT) disability score (higher scores indicate greater disability). The model was then used to simulate changes in total serum IgG concentrations and the PD endpoint for patients with CIDP. Dosing scenarios simulated were 6 months of IVIG 10% or 3 months of IVIG 10% followed by 9 months of fSCIG 10% at dosages of 0.4, 0.8, and 1.0 g/kg every 2 weeks, 1.0 and 2.0 g/kg every 3 weeks, and 0.4, 0.8, 1.0, and 2.0 g/kg every 4 weeks.

RESULTS

Our results showed that higher doses and more frequent IVIG/fSCIG 10% administration were associated with a lower mean probability of increased adjusted INCAT score (i.e., lower probability of relapse), remaining < 50% in all simulations except the 0.4 g/kg every 4 weeks dosage. The probability of increased adjusted INCAT score tended to be higher toward the end of the dosing interval for patients treated less frequently.

DISCUSSION: Higher and more frequent dosing may result in more consistent treatment efficacy in patients with CIDP.