Angio-hÉmatologie et Clinique des Anticoagulants, CREATIF, Hôpital Lariboisière, AP-HP Paris, Faculté de Médecine Paris-VII, Paris, France.
Target Oncol. 2012 Mar;7 Suppl 1:S35-42. doi: 10.1007/s11523-011-0194-5. Epub 2012 Jan 25.
The development of biosimilar versions of low molecular weight heparins (LMWHs) raises real medical concerns. To illustrate this, we have chosen as an example the specific clinical setting of antithrombotic management of acute coronary syndromes (ACS). In this indication, the LMWH enoxaparin has consistently shown its superiority in terms of efficacy when compared to unfractionated heparin (UFH) and in a number of direct or indirect comparisons to other LMWHs. For this reason, enoxaparin has become the gold standard for anticoagulation in cardiology, recommended by practice guidelines and extensively used in everyday practice. We are concerned by the fact that some patients might be treated with a biosimilar copy of enoxaparin, on the basis of simplified criteria that are not specific enough to differentiate between different available LMWHs and are thus unable to differentiate between enoxaparin and a biosimilar. In the absence of evidence from clinical trials, especially in ACS, we believe that it is difficult to ensure that the benefit/risk ratio of enoxaparin and its copy are equivalent. In addition to efficacy, safety issues also have to be taken into consideration, since biosimilars consist of glycan chain mixtures that exhibit specific immunoallergic features. Contamination of raw material with other glycans or xenobiotic material during extraction and fractionation may trigger potentially harmful immune reactions.
低分子量肝素（LMWH）生物类似药的发展引发了真正的医学关注。为了说明这一点，我们选择了抗栓治疗急性冠状动脉综合征（ACS）的特定临床环境作为示例。在该适应证中，与未分级肝素（UFH）相比，LMWH 依诺肝素在疗效方面表现出一致性优势，并且在许多直接或间接比较中也优于其他 LMWH。出于这个原因，依诺肝素已成为心脏病学抗凝治疗的金标准，被实践指南推荐，并在日常实践中广泛使用。我们担心的是，一些患者可能会根据简化标准而接受依诺肝素的生物类似药治疗，这些标准不够具体，无法区分不同的可用 LMWH，因此无法区分依诺肝素和生物类似药。在缺乏临床试验证据的情况下，特别是在 ACS 中，我们认为难以确保依诺肝素及其类似药的获益/风险比相当。除了疗效，还需要考虑安全性问题，因为生物类似药由具有特定免疫过敏特征的聚糖链混合物组成。在提取和分级过程中，原材料与其他糖或异源物质的污染可能会引发潜在的有害免疫反应。
