Novel thrombopoietic agents - A review of their use in idiopathic thrombocytopenic purpura
Novel thrombopoietic agents - A review of their use in idiopathic thrombocytopenic purpura
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DOI：
10.2165/00003495-200868070-00002
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发表时间：
2008-01-01
期刊：
影响因子：
11.5
通讯作者：
Amadori, Sergio
中科院分区：
文献类型：
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作者：
Stasi, Roberto;Evangelista, Maria L.;Amadori, Sergio
特发性血小板减少性紫癜(ITP)的潜在问题传统上被认为是加速的血小板破坏。然而，最近的研究表明，ITP的病理生理机制更加复杂，血小板生成障碍已成为导致血小板减少的机制之一。基于这些原因，第二代促血小板生成剂已被用于临床试验，以刺激对标准治疗无效的ITP患者的血小板生成。这些新分子在结构上与促血小板生成素(TPO)没有相似之处，但仍然与TPO受体结合并激活。两种TPO受体激动剂的研究已经完成：罗米普罗替姆(以前的AMG531)和eltrombopg(以前的SB497115)。罗米普替丁是一种被定义为多肽的重组蛋白。最近公布的I-II期试验结果表明，在大多数接受治疗的患者中，每周一次皮下注射罗米普替明1-6周，可使血小板增加一倍，并增加到>；50×10(9)/L，且副作用最小。艾尔马波是一种口服的小型有机化合物。在一项随机、双盲、安慰剂对照的III期试验中，ITP患者每天接受安慰剂或eltrombopg 50 mg的口服治疗。在接受电疗的患者中有59%的患者观察到了血小板反应，在安慰剂组中有16%的患者观察到了血小板反应。没有发现明显的不良反应。其他正在开发中的血栓生成剂，如AKR-501(以前的YM477)，在健康志愿者中似乎很有希望。正在进行的第三阶段临床试验将揭示这些药物在脾切除前治疗ITP和长期维持治疗方面的潜力，以及它们与标准护理治疗相比的相对好处。
The underlying problem in idiopathic thrombocytopenic purpura (ITP) has traditionally been-recognized as accelerated platelet destruction. However, recent studies have provided evidence that the pathophysiology of ITP is more complex, and impaired platelet production has emerged as one of the mechanisms contributing to the thrombocytopenia. On these grounds, second-generation thrombopoietic agents have been used in clinical trials to stimulate platelet production in ITP patients who are not responsive to standard treatments. These new molecules bear no structural resemblance to thrombopoietin (TPO) but still bind and activate the TPO receptor. Studies have been completed for two TPO receptor agonists: romiplostim (formerly AMG 531) and eltrombopag (formerly SB497115). Romiplostim is a recombinant protein defined as a peptibody. Results of phase I-II trials published recently demonstrated that romiplostim given as a weekly subcutaneous injection for 1-6 weeks results in doubling of platelet counts and an increase to > 50 x 10(9)/L in most treated patients with minimal adverse effects. Eltrombopag is an orally available, small organic compound. In a randomized, double-blind, placebo-controlled phase III trial, ITP patients were given daily oral treatment with placebo or eltrombopag 50 mg. Platelet responses were observed in 59% of eltrombopag-treated patients and in 16% of patients in the placebo arm. No significant adverse events were seen. Other thrombopoietic agents in development, such as AKR-501 (formerly YM 477), appear promising in healthy volunteers. Ongoing phase III clinical trials will reveal the potential of these agents in the management of ITP prior to splenectomy and for long-term maintenance therapy, as well as their relative benefit compared with standard of care treatment.