免疫球蛋白G剂量-暴露-疗效反应在慢性炎性脱髓鞘性多发性神经根神经病患者中的研究。
完整摘要 · 中文译文
引言：静脉注射免疫球蛋白（IVIG）10%和透明质酸酶辅助皮下注射免疫球蛋白（fSCIG）10%均被用作慢性炎性脱髓鞘性多发性神经根神经病（CIDP）患者的维持治疗。由于该病罕见，关于这些治疗的剂量、暴露与临床结局之间关系的数据很少。本分析旨在描述IVIG 10%和fSCIG 10%在CIDP中剂量、暴露与临床疗效之间的关系。 材料与方法：数据汇总自两项3期研究，分别纳入CIDP患者（NCT02549170；ADVANCE-CIDP 1）和多灶性运动神经病（NCT00666263）患者。开发了序贯群体药代动力学（PK）-药效动力学（PD）模型，以描述血清总免疫球蛋白G（IgG）的PK与作为PD终点的校正后炎性神经病病因和治疗（INCAT）残疾评分升高概率（评分越高表示残疾越重）之间的PK-PD关系。随后使用该模型模拟CIDP患者总血清IgG浓度和PD终点的变化。模拟的给药方案为：IVIG 10%治疗6个月，或IVIG 10%治疗3个月后接续fSCIG 10%治疗9个月，剂量分别为每2周0.4、0.8和1.0 g/kg，每3周1.0和2.0 g/kg，以及每4周0.4、0.8、1.0和2.0 g/kg。 结果：我们的结果显示，较高剂量和更频繁的IVIG/fSCIG 10%给药与校正后INCAT评分升高的平均概率较低相关（即较低的p 复发概率），除0.4 g/kg每4周剂量外，所有模拟中均保持在<50%。对于治疗频率较低的患者，调整后INCAT评分升高的概率在给药间期末尾趋于更高。 讨论：更高且更频繁的给药可能使CIDP患者的治疗效果更为一致。
完整摘要 · 英文原文
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.