Department of Pediatric Hematology and Oncology, Hannover Medical School, Hannover, Germany.
Hamostaseologie. 2022 Apr;42(2):104-115. doi: 10.1055/a-1727-1384. Epub 2022 Apr 29.
Emicizumab is the first approved nonreplacement therapy for bleeding prophylaxis in hemophilia A (HA) patients. In 2018, it was licensed for HA patients with inhibitors, subsequently followed by an "European Medicines Agency (EMA)" approval for patients with severe HA in the absence of inhibitors in 2019. This is immediately raising the question whether emicizumab is suitable as a first-line treatment for all pediatric patients with severe HA. In this review, we want to discuss what we have, what we know, and what we would like to know. Severe HA is characterized by severe spontaneous and traumatic bleedings, particularly into muscles and joints leading to chronic joint damage. Standard of care is the regular, prophylactic replacement of factor VIII to prevent bleedings. Due to approval of emicizumab-the first nonreplacement therapy for bleeding prophylaxis-in HA patients with inhibitors, and severe HA patients without inhibitors, it is of pivotal interest whether emicizumab could be the first-line treatment in all pediatric patients with severe HA. Clinical trials and real-world observational studies could demonstrate a good efficacy and safety for bleeding prevention during emicizumab treatment in HA patients with and without inhibitors. This clearly indicates that emicizumab could improve HA treatment. However, some crucial and critical questions are remaining with regard to the use of emicizumab. Some of this missing information is already under investigation in the context of clinical trials. Until getting finalized data to shed insights into the points that are currently being discussed, there is a variety of expert and expert group recommendations, which are tackling questions concerning the treatment of HA patients. This review will address major information that is already available, but will also focus on important points that remain to be elucidated in the context of HA treatment.
依库珠单抗是第一种获批用于预防出血的非替代疗法，可用于治疗 A 型血友病（HA）患者。2018 年，该药获批用于有抑制剂的 HA 患者，随后于 2019 年，在无抑制剂的重度 HA 患者中获得“欧洲药品管理局（EMA）”批准。这立即引发了一个问题，即依库珠单抗是否适合作为所有重度 HA 儿科患者的一线治疗药物。在本综述中，我们希望讨论我们已经了解、已知和想要了解的内容。重度 HA 的特征是严重自发性和创伤性出血，尤其是肌肉和关节出血，导致慢性关节损伤。标准治疗是定期预防性输注凝血因子 VIII 以预防出血。由于依库珠单抗获批用于有抑制剂和无抑制剂的 HA 患者的出血预防治疗，它是第一种非替代疗法，因此，依库珠单抗能否成为所有重度 HA 儿科患者的一线治疗药物至关重要。临床试验和真实世界观察性研究表明，依库珠单抗治疗有抑制剂和无抑制剂的 HA 患者可有效预防出血，且安全性良好。这清楚地表明依库珠单抗可改善 HA 的治疗效果。然而，在依库珠单抗的使用方面仍存在一些关键和重要的问题。一些关键信息已经在临床试验中进行了研究。在获得最终数据以深入了解目前正在讨论的问题之前，各种专家和专家组建议正在处理 HA 患者的治疗问题。本综述将主要讨论已有的重要信息，同时还将重点关注 HA 治疗中仍需阐明的重要问题。
