Oldenburg Johannes, Benson Gary, Chowdary Pratima, Halimeh Susan, Matsushita Tadashi, Nørland Anne, Wahid Mohd Nawi, Nemes Laszlo
Institute for Experimental Haematology and Transfusion Medicine, University of Bonn, Bonn, Germany.
Department of Haematology, Belfast City Hospital, Belfast, UK.
Haemophilia. 2023 Nov;29(6):1475-1482. doi: 10.1111/hae.14864. Epub 2023 Sep 20.
Turoctocog alfa pegol (N8-GP) is a glycoPEGylated, extended half-life (EHL), human recombinant factor VIII (FVIII) approved for the treatment and prevention of bleeding episodes in patients with haemophilia A. Since its launch in August 2019, > 800 patients have been treated worldwide.
To present data from identified post-marketing cases of less-than-expected FVIII activity in previously treated patients (PTPs) without inhibitors after switching to N8-GP.
The post-marketing safety database was searched using keywords such as 'coagulation FVIII level decreased'. Identified cases reported prior to 13 October 2021 were included in this report. Cases in which patients had FVIII inhibitors were excluded.
Here we report 14 cases of less-than-expected FVIII activity. Details varied greatly amongst the cases. At presentation, FVIII activity ranged from 1% (15 min post-dose) to 51% (2 days post-dose). Seven patients experienced bleeding episodes after switching to N8-GP with heterogeneity in bleeding presentations. Six out of seven patients who were tested for anti-PEG IgG and/or IgM antibodies were positive. In all known cases, FVIII activity returned to the expected range when switched to an alternative FVIII replacement product.
In conclusion, the 14 reported cases of less-than-expected FVIII activity, without presence of detectable FVIII inhibitors, presented with heterogenous characteristics, and wide variations in FVIII activity and anti-PEG antibody titre. FVIII activity returned to the expected range after switching to alternative FVIII products. In line with WFH guidelines, monitoring of FVIII activity can ensure FVIII activity in the expected range. The safety surveillance of N8-GP continues.
聚乙二醇化重组人凝血因子VIII（N8-GP）是一种聚乙二醇化、半衰期延长的人重组凝血因子VIII，已被批准用于治疗和预防A型血友病患者的出血发作。自2019年8月上市以来，全球已有超过800名患者接受了治疗。
展示在既往接受治疗且无抑制剂的患者（PTPs）转换为N8-GP后，所发现的VIII因子活性低于预期的上市后病例数据。
使用“凝血因子VIII水平降低”等关键词搜索上市后安全数据库。本报告纳入了2021年10月13日前报告的已识别病例。排除患者有VIII因子抑制剂的病例。
我们在此报告14例VIII因子活性低于预期的病例。各病例的详细情况差异很大。就诊时，VIII因子活性范围为1%（给药后15分钟）至51%（给药后2天）。7名患者在转换为N8-GP后发生出血发作，出血表现各异。在接受抗聚乙二醇IgG和/或IgM抗体检测的7名患者中，有6名呈阳性。在所有已知病例中，转换为替代的VIII因子替代产品后，VIII因子活性恢复到预期范围。
总之，报告的这14例VIII因子活性低于预期的病例，在未检测到VIII因子抑制剂的情况下，具有异质性特征，VIII因子活性和抗聚乙二醇抗体滴度差异很大。转换为替代的VIII因子产品后，VIII因子活性恢复到预期范围。根据世界血友病联盟指南，监测VIII因子活性可确保其活性处于预期范围内。N8-GP的安全性监测仍在继续。
