Lunn Michael P, Ellis Lauren, Hadden Robert D, Rajabally Yusuf A, Winer John B, Reilly Mary M
MRC Centre for Neuromuscular Diseases, UCL Institute of Neurology and National Hospital for Neurology and Neurosurgery, London, UK.
King's College Hospital, London, UK.
J Peripher Nerv Syst. 2016 Mar;21(1):33-7. doi: 10.1111/jns.12158.
Dosing guidelines for immunoglobulin (Ig) treatment in neurological disorders do not consider variations in Ig half-life or between patients. Individualization of therapy could optimize clinical outcomes and help control costs. We developed an algorithm to optimize Ig dose based on patient's response and present this here as an example of how dosing might be individualized in a pharmacokinetically rational way and how this achieves potential dose and cost savings. Patients are "normalized" with no more than two initial doses of 2 g/kg, identifying responders. A third dose is not administered until the patient's condition deteriorates, allowing a "dose interval" to be set. The dose is then reduced until relapse allowing dose optimization. Using this algorithm, we have individualized Ig doses for 71 chronic inflammatory neuropathy patients. The majority of patients had chronic inflammatory demyelinating polyradiculoneuropathy (n = 39) or multifocal motor neuropathy (n = 24). The mean (standard deviation) dose of Ig administered was 1.4 (0.6) g/kg, with a mean dosing interval of 4.3 weeks (median 4 weeks, range 0.5-10). Use of our standardized algorithm has allowed us to quickly optimize Ig dosing.
神经疾病中免疫球蛋白(Ig)治疗的给药指南未考虑Ig半衰期的差异或患者之间的差异。治疗个体化可优化临床疗效并有助于控制成本。我们开发了一种基于患者反应优化Ig剂量的算法,并在此展示,作为如何以药代动力学合理的方式实现给药个体化以及如何实现潜在的剂量和成本节约的示例。患者用不超过两剂初始剂量2 g/kg进行“标准化”,以识别有反应者。直到患者病情恶化才给予第三剂,从而设定“给药间隔”。然后降低剂量直到复发,从而实现剂量优化。使用该算法,我们为71例慢性炎性神经病患者实现了Ig剂量个体化。大多数患者患有慢性炎性脱髓鞘性多发性神经根神经病(n = 39)或多灶性运动神经病(n = 24)。给予的Ig平均(标准差)剂量为1.4(0.6)g/kg,平均给药间隔为4.3周(中位数4周,范围0.5 - 10周)。使用我们的标准化算法使我们能够快速优化Ig给药。