Department of Pharmaceutical Outcomes and Policy, College of Pharmacy, University of Florida, Gainesville, FL, USA.
J Asthma Allergy. 2012;5:1-9. doi: 10.2147/JAA.S29811. Epub 2012 May 3.
Omalizumab is a monoclonal antibody, indicated for the treatment of severe allergic asthma. In Europe, there have been concerns about the cardiovascular safety of omalizumab. The objective of this study was to analyze the association between omalizumab and arterial thrombotic events in a spontaneous adverse drug reaction reporting database in the US.
Reports of arterial thrombotic events submitted to the US Food and Drug Administration's Adverse Event Reporting System (AERS) between 2004 and 2011 were retrieved and analyzed by the reporting odds ratio data mining algorithm. The reporting odds ratio of arterial thrombotic events for omalizumab was compared with specific asthma medications and all drugs in the AERS. Values ≥2 were considered significant safety signals. The Medical Dictionary for Regulatory Activities Preferred Terms were used to identify arterial thrombotic events (eg, stroke, myocardial infarction).
In total, 293,783 reports of arterial thrombotic events were retrieved (about 2% of all adverse drug reaction reports), corresponding to 2274 asthma drug-arterial thrombotic events pairs (omalizumab, 222; inhaled corticosteroids [ICS], 131; long-acting beta-agonists [LABA], 102; single-device combination ICS-LABA, 506; inhaled short-acting beta-agonists [SABA], 475; oral SABA, 6; inhaled antimuscarinics [AMC], 477; single-device combination AMC-SABA, 127; xanthines, 50; leukotriene modifiers, 174; and mast cell stabilizers, 4). Reporting odds ratio and 95% confidence interval values for omalizumab compared with other asthma drugs and all drugs in AERS were 2.75 (2.39-316) and 1.09 (0.95-1.24), respectively. Omalizumab ranked second after ICS in the risk of arterial thrombotic events, followed by AMC, AMC-SABA, and ICS-LABA.
Omalizumab is associated with higher than expected reporting of arterial thrombotic events in asthmatic patients. This hypothesis needs further testing in robust epidemiological studies.
奥马珠单抗是一种单克隆抗体，用于治疗严重的过敏性哮喘。在欧洲，人们对奥马珠单抗的心血管安全性表示担忧。本研究的目的是分析在美国自发药物不良反应报告数据库中奥马珠单抗与动脉血栓栓塞事件之间的关联。
从 2004 年至 2011 年，从美国食品和药物管理局不良事件报告系统（AERS）中检索到动脉血栓栓塞事件报告，并通过报告比值比数据挖掘算法进行分析。奥马珠单抗发生动脉血栓栓塞事件的报告比值比与 AERS 中的特定哮喘药物和所有药物进行比较。比值≥2 被认为是显著的安全信号。使用监管活动医学词典首选术语来识别动脉血栓栓塞事件（如中风、心肌梗死）。
共检索到 293783 例动脉血栓栓塞事件报告（约占所有药物不良反应报告的 2%），对应于 2274 例哮喘药物-动脉血栓栓塞事件对（奥马珠单抗 222 例；吸入皮质类固醇[ICS]131 例；长效β-激动剂[LABA]102 例；单一装置组合 ICS-LABA506 例；吸入短效β-激动剂[SABA]475 例；口服 SABA6 例；吸入抗毒蕈碱药[AMC]477 例；单一装置组合 AMC-SABA127 例；黄嘌呤 50 例；白三烯调节剂 174 例；和肥大细胞稳定剂 4 例）。与其他哮喘药物和 AERS 中的所有药物相比，奥马珠单抗的报告比值比和 95%置信区间值分别为 2.75（2.39-316）和 1.09（0.95-1.24）。奥马珠单抗在动脉血栓栓塞事件风险方面仅次于 ICS，其次是 AMC、AMC-SABA 和 ICS-LABA。
奥马珠单抗与哮喘患者动脉血栓栓塞事件的报告发生率高于预期相关。这一假设需要在稳健的流行病学研究中进一步验证。
