Fondazione IRCCS Ca' Granda-Ospedale Maggiore Policlinico, UOC Medicina Generale, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Milan, Italy. Electronic address: https://twitter.com/AbbattistaMaria.
Department of Biomedical Sciences for Health, Università degli Studi di Milano, Milan, Italy.
J Thromb Haemost. 2023 Mar;21(3):546-552. doi: 10.1016/j.jtha.2023.01.010. Epub 2023 Jan 16.
Safety concerns for an increased risk of thrombotic complications in patients with hemophilia A have been pointed out, particularly during nonreplacement treatment with emicizumab and concomitant bypassing agents. Surveillance with the Roche Global Database reporting adverse events for emicizumab has been discontinued on May 2021.
The objective of this study was to evaluate the reporting rate of hemorrhagic and thrombotic adverse drug reactions (ADRs) associated with nonreplacement (emicizumab) and replacement extended half-life (EHL) factor VIII (FVIII) products as retrieved from the EudraVigilance database.
Total ADR reported during treatment with emicizumab or EHL FVIII products from January 1 to December 31, 2021, were collected. The proportional reporting ratio and the reporting odds ratio (ROR) with their 95% CIs were calculated to express the hemorrhagic and thrombotic ADR reporting frequency ratio between emicizumab and EHL FVIII products.
Overall, 406 and 376 ADRs were reported for emicizumab and for EHL FVIII products, respectively. Hemorrhagic and thrombotic ADRs were 232 and 24 for emicizumab and 275 and 9 for the EHL FVIII products. Approximately 25% of thrombotic ADRs were reported concomitantly with eptacog alfa. ROR of 0.49 (95% CI, 0.36-0.66) for hemorrhagic and of 2.56 (95% CI, 1.18-5.59) for thrombotic ADRs were obtained for emicizumab compared with EHL FVIII products.
The analysis of 2021 EudraVigilance reports shows a lower reporting rate of hemorrhagic ADR vs a higher reporting rate of thrombotic ADR for emicizumab than for EHL FVIII products. These signals stress the importance of monitoring novel drugs in hemophilia, particularly when administered in association with bypassing agents.
有报道称，甲型血友病患者在接受依美珠单抗等非替代治疗和同时使用旁路制剂时，存在血栓并发症风险增加的安全隐患。罗氏全球不良事件报告数据库自 2021 年 5 月起停止报告依美珠单抗的安全性数据。
本研究旨在评估从欧洲药品管理局药物警戒数据库中检索到的非替代（依美珠单抗）和替代延长半衰期（EHL）VIII 因子（FVIII）产品治疗期间出血和血栓不良药物反应（ADR）的报告率。
收集 2021 年 1 月 1 日至 12 月 31 日期间使用依美珠单抗或 EHL FVIII 产品治疗时报告的所有 ADR。计算比例报告比值和报告比值比（ROR）及其 95%置信区间，以表示依美珠单抗和 EHL FVIII 产品之间出血和血栓 ADR 的报告频率比值。
共报告 406 例和 376 例与依美珠单抗和 EHL FVIII 产品相关的 ADR。依美珠单抗组报告了 232 例出血性 ADR 和 24 例血栓性 ADR，EHL FVIII 产品组报告了 275 例出血性 ADR 和 9 例血栓性 ADR。约 25%的血栓性 ADR 是在同时使用eptacog alfa 时报告的。与 EHL FVIII 产品相比，依美珠单抗的出血性 ADR 的 ROR 为 0.49（95%CI，0.36-0.66），血栓性 ADR 的 ROR 为 2.56（95%CI，1.18-5.59）。
对 2021 年欧洲药品管理局药物警戒数据库报告的分析显示，依美珠单抗的出血性 ADR 报告率较低，而血栓性 ADR 报告率较高。这些信号强调了在血友病中监测新型药物的重要性，特别是当与旁路制剂联合使用时。
