Resposta imunoglobulina G dose-exposição-eficácia em pacientes com poliradiculoneuropatia desmielinizante inflamatória crônica

O que aconteceu

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

Trecho mantido em inglês: a tradução automática não passou na conferência de números.

O que encontraram

Nossos resultados mostraram que doses mais elevadas e a administração mais frequente de IVIG/fSCIG 10% estiveram associadas a uma menor probabilidade média de aumento do escore INCAT ajustado (i.e., menor probabilidade de recidiva), permanecendo < 50% em todas as simulações, exceto na dosagem de 0,4 g/kg a cada 4 semanas. A probabilidade de aumento do escore INCAT ajustado tendeu a ser maior no final do intervalo de dosagem para os pacientes tratados com menos frequência.