Abstract：
OBJECTIVE: Omalizumab is an anti-immunoglobulin E (IgE) monoclonal antibody that was first approved by the United States (US) Food and Drug Administration (FDA) for the treatment of allergic asthma in 2003. The pivotal trials supporting the initial approval of omalizumab used dosing determined by patient\'s baseline IgE and body weight, with the goal of reducing the mean free IgE level to approximately 25 ng/mL or less. While the underlying parameters supporting the dosing table remained the same, subsequent studies and analyses have resulted in approved alternative versions of the dosing table, including the European Union (EU) asthma dosing table, which differs in weight bands and maximum allowable baseline IgE and omalizumab dose. In this study, we leveraged modelling and simulation approaches to predict and compare the free IgE reduction and forced expiratory volume in 1 second (FEV1) improvement with omalizumab dosing based on the US and EU asthma dosing tables.
METHODS: Previously established population pharmacokinetic-IgE and IgE-FEV1 models were used to predict and compare post-treatment free IgE and FEV1 based on the US and EU dosing tables. Clinical trial simulations (with virtual asthma populations) and Monte Carlo simulations were performed to provide both breadth and depth in the comparisons.
RESULTS: The US and EU asthma dosing tables were predicted to result in generally comparable free IgE suppression and FEV1 improvement.
CONCLUSIONS: Despite the similar free IgE and FEV1 outcomes from simulations, this has not been clinically validated with respect to the registrational endpoint of reduction in annualized asthma exacerbations.
METHODS: Previously established population pharmacokinetic-IgE and IgE-FEV1 models were used to predict and compare post-treatment free IgE and FEV1 based on the US and EU dosing tables. Clinical trial simulations (with virtual asthma populations) and Monte Carlo simulations were performed to provide both breadth and depth in the comparisons.
RESULTS: The US and EU asthma dosing tables were predicted to result in generally comparable free IgE suppression and FEV1 improvement.
CONCLUSIONS: Despite the similar free IgE and FEV1 outcomes from simulations, this has not been clinically validated with respect to the registrational endpoint of reduction in annualized asthma exacerbations.
摘要：
目的：Omalizumab是一种抗免疫球蛋白E（IgE）单克隆抗体，于2003年首次被美国（US）食品药品监督管理局（FDA）批准用于治疗过敏性哮喘。支持奥马珠单抗初步批准的关键试验使用由患者基线IgE和体重确定的剂量，目标是将平均游离IgE水平降低至约25ng/mL或更低。虽然支持剂量表的基本参数保持不变，随后的研究和分析产生了批准的剂量表的替代版本，包括欧盟（EU）哮喘剂量表，在体重带和最大允许基线IgE和奥马珠单抗剂量方面有所不同。在这项研究中,我们利用建模和模拟方法,根据美国和欧盟哮喘给药表,预测和比较奥马珠单抗给药对游离IgE减少和1秒用力呼气量(FEV1)改善的影响.
方法：使用先前建立的群体药代动力学IgE和IgE-FEV1模型，根据美国和欧盟给药表预测和比较治疗后无IgE和FEV1。进行临床试验模拟(具有虚拟哮喘群体)和蒙特卡洛模拟以提供比较的广度和深度。
结果：预计美国和欧盟哮喘给药表可导致一般相当的游离IgE抑制和FEV1改善。
结论：尽管来自模拟的游离IgE和FEV1结果相似，关于哮喘年度加重减少的注册终点,这一点尚未得到临床验证.
方法：使用先前建立的群体药代动力学IgE和IgE-FEV1模型，根据美国和欧盟给药表预测和比较治疗后无IgE和FEV1。进行临床试验模拟(具有虚拟哮喘群体)和蒙特卡洛模拟以提供比较的广度和深度。
结果：预计美国和欧盟哮喘给药表可导致一般相当的游离IgE抑制和FEV1改善。
结论：尽管来自模拟的游离IgE和FEV1结果相似，关于哮喘年度加重减少的注册终点,这一点尚未得到临床验证.
