Oncologie

, Volume 13, Issue 5, pp 239–246 | Cite as

Biosimilaires d’héparine de bas poids moléculaire: quel degré de similarité pour quel bénéfice clinique ?

Synthèse / Review Article

Résumé

L’apparition de biosimilaires d’héparines de bas poids moléculaire (HBPM) soulève une réelle inquiétude médicale. Pour illustrer nos interrogations autour de ces médicaments biogénériques, nous avons pris l’exemple du contexte clinique spécifique associé à la prise en charge antithrombotique des syndromes coronaires aigus (SCA). Dans cette indication, une HBPM, l’énoxaparine, a démontré, demanière réitérée dans des études de phase 3, une efficacité supérieure à l’héparine non fractionnée (HNF) ainsi qu’en comparaison directe ou indirecte avec certaines autres HBPM. C’est en raison de cette particularité en termes de bénéfice clinique que l’énoxaparine est devenue l’HBPM de référence en cardiologie, recommandée et utilisée de manière extensive dans la prise en charge des SCA. Nous sommes préoccupés par le fait que certains patients puissent être traités dans le cadre d’un SCA avec une copie de l’énoxaparine, approuvée sur la base de critères simplifiés dont nous avons démontré l’absence ou la faible capacité à différencier les HBPM entre elles, et qui de surcroît ne permettraient pas de différencier l’énoxaparine d’un biosimilaire. En l’absence d’essais cliniques comparatifs directs, il nous paraît difficile de garantir l’équivalence du rapport bénéfice/risque d’un biosimilaire comparativement à l’énoxaparine, en particulier dans l’indication spécifique des SCA. En effet, outre l’efficacité, la sécurité d’emploi du biosimilaire est à considérer avec attention: les héparines sont des mélanges de chaînes glycaniques présentant des caractéristiques immunoallergiques très spécifiques. De plus, la contamination des matières premières par d’autres composés ou d’autres glycanes lors de l’extraction de ces molécules est susceptible de déclencher des réactions immunitaires potentiellement dramatiques.

Mots clés

HBPM Héparine Générique Biosimilaire Énoxaparine Syndrome coronarien aigu TIH 

Low molecular weight heparin biosimilars: how much similarity for how much clinical benefit?

Abstract

The development of biosimilar versions of low molecular weight heparins (LMWHs) raises a real medical concern. To illustrate our concerns regarding biosimilars, we chose the example of the specific clinical setting associated to the antithrombotic management of the acute coronary syndromes (ACS). In this specific indication, the LMWH enoxaparin has consistently shown its superiority in terms of efficacy when compared to unfractionated heparin (UFH) and in some direct or indirect comparison to other LMWHs. This is because of these particular clinical evidences that enoxaparin was considered as the gold standard for anticoagulation in cardiology and became almost universally used in ACS management. We are concerned by the fact that some patients might be treated by a generic copy of enoxaparin, on the basis of simplified criteria which were shown not to be specific enough to enable differentiation among LMWHs, thus, are unable to differentiate between enoxaparin and a biosimilar, in particular. Without any evidence from clinical trials, especially in ACS indication, we believe it is hard to ensure that the benefitrisk ratio between enoxaparin and its copy be equivalent. Indeed along with efficacy, safety issues have to be taken into consideration: biosimilars consist of glycan chain mixtures that exhibit specific immunoallergic features. Furthermore, the contamination of raw material with other components or other glycans during molecule extraction may trigger potentially harmful immune reactions.

Keywords

LMWH Heparin Generic drug Biosimilar Enoxaparin ACS Acute coronary syndrome HIT 

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Copyright information

© Springer Verlag France 2011

Authors and Affiliations

  1. 1.Angiohématologie et clinique des anticoagulants « CREATIF », hôpital LariboisièreAP-HP Paris, faculté de médecine Paris-VIIParisFrance
  2. 2.Laboratoire de thrombose et d’athérosclérose, institut des vaisseaux et du sanghôpital Lariboisière, ParisParisFrance

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