Kornmann Oliver, Watz Henrik, Fuhr Rainard, Krug Norbert, Erpenbeck Veit J, Kaiser Guenther
Pulmonary Department, Internal Medicine, University Hospital Mainz, Langenbeckstraße 1, 55131 Mainz, Germany.
Pulmonary Research Institute at LungenClinic Grosshansdorf, Airway Research Center North, Member of the German Center for Lung Research, Grosshansdorf, Germany.
Pulm Pharmacol Ther. 2014 Aug;28(2):149-53. doi: 10.1016/j.pupt.2014.03.003. Epub 2014 Mar 18.
When first approved in the European Union (EU), the omalizumab dosing table had upper bodyweight and IgE limits of 150 kg and 700 IU/mL, respectively. In this study, we assessed the safety, pharmacokinetics (PK) and pharmacodynamics (PD) of omalizumab in patients with IgE/bodyweight combinations above those in the original dosing table.
A multicentre, open-label, parallel-group study assessed the safety, PK and PD of omalizumab in 32 patients with mild-to-moderate allergic (IgE-mediated) asthma. Patients received two subcutaneous injections of omalizumab at one of three dosage levels (450, 525, or 600 mg), chosen according to baseline IgE (300-2000 IU/mL) and bodyweight (40-150 kg), with a 14-day interval between injections.
Overall, 69 adverse events (AEs), none of them serious, were reported by 26 (81.3%) patients. Analysis of laboratory measurements, vital signs and ECG data revealed no adverse findings of clinical relevance. The PK profile was consistent with previous data for lower doses. Mean maximum decrease of free IgE from screening was ≥99% for all three doses, and mean free IgE concentrations remained <25 ng/mL for at least 2 weeks after the second dose. The reductions in free IgE were consistent with levels previously associated with clinical improvements.
The safety and PK/PD findings from this study are consistent with previous data, and supported the extension of the omalizumab dosing table to include those patients with higher IgE/bodyweight combinations. Clinical trial registry and registration number: clinicaltrials.gov (NCT00546143).
在欧盟首次获批时，奥马珠单抗的剂量表中，体重上限和IgE上限分别为150千克和700国际单位/毫升。在本研究中，我们评估了奥马珠单抗在IgE/体重组合高于原始剂量表中的患者中的安全性、药代动力学（PK）和药效学（PD）。
一项多中心、开放标签、平行组研究评估了奥马珠单抗在32例轻至中度过敏性（IgE介导）哮喘患者中的安全性、PK和PD。患者根据基线IgE（300 - 2000国际单位/毫升）和体重（40 - 150千克），在三个剂量水平（450、525或600毫克）之一接受两次皮下注射奥马珠单抗，两次注射间隔14天。
总体而言，26例（81.3%）患者报告了69起不良事件（AE），均不严重。实验室测量、生命体征和心电图数据分析未发现具有临床相关性的不良结果。PK曲线与先前较低剂量的数据一致。所有三个剂量组从筛查时起游离IgE的平均最大降幅均≥99%，第二次注射后至少2周内游离IgE平均浓度保持<25纳克/毫升。游离IgE的降低与先前与临床改善相关的水平一致。
本研究的安全性和PK/PD结果与先前数据一致，并支持将奥马珠单抗剂量表扩展至包括IgE/体重组合更高的患者。临床试验注册及注册号：clinicaltrials.gov（NCT00546143）。
