Promacta获准用于治疗接受丙肝治疗者的血小板减少症

圣路易斯(MD Consult)——2012年11月19日，葛兰素史克(GlaxoSmithKline)宣布美国食品药品管理局(FDA)已正式批准Promacta(伊屈泼帕)用于治疗慢性丙肝患者的血小板减少症，以便这些患者能够启动并维持以干扰素为基础的肝病治疗。Promacta是一种促血小板生成素受体激动剂，之前已经获准用于治疗慢性免疫性(特发性)血小板减少性紫癜患者的血小板减少症。

Promacta新适应证的获批是基于2项随机、双盲、安慰剂对照、多中心、Ⅲ期临床试验的结果，这些试验总共纳入了1,512例血小板计数＜75,000/μl的患者。其中一项试验采用聚乙二醇化干扰素α-2a(派罗欣)联合利巴韦林进行抗病毒治疗，另一项试验则采用聚乙二醇化干扰素α-2b(佩乐能)加利巴韦林的联合用药方案。结果表明，Promacta联合以干扰素为基础的抗病毒治疗能提高丙肝患者获得持续病毒学应答或病毒治愈的机会。

在比较Promacta与安慰剂的临床试验中，最常见的不良反应包括：贫血(40% vs. 35%)、发热(30% vs. 24%)、乏力(28% vs. 23%)、头痛(21% vs. 20%)、恶心(19% vs. 14%)、腹泻(19% vs. 11%)、食欲不振(18% vs. 14%)、流感样不适(18% vs. 16%)、虚弱(16% vs. 13%)、失眠(16 % vs. 15%)、咳嗽 (15% vs. 12%)、瘙痒(15% vs. 13%)、寒战 (14% vs. 9%)、肌肉疼痛 (12% vs. 10%)、脱发(10% vs. 6%)和外周性水肿 (10% vs. 5%)。

Promacta的产品说明书中含有一个关于肝脏毒性的黑框警告。Promacta联合干扰素及利巴韦林用于慢性丙肝患者，可能会增加肝功能失代偿的风险。因此，接受Promacta治疗的患者必须进行血清肝功能测试的定期监测。

Promacta用于慢性丙肝相关性血小板减少症患者也存在一些局限性。Promacta不应用于以使血小板计数恢复正常为目的的治疗。Promacta仅可用于血小板减少症程度妨碍了启动干扰素治疗或者妨碍了维持最佳干扰素治疗的慢性丙肝患者。尚不清楚Promacta与已经获准用于基因1型慢性丙肝感染者的直接作用抗病毒药物联合使用的安全性和疗效。

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ST LOUIS (MD Consult) - On November 19, 2012, GlaxoSmithKline announced that the US Food and Drug Administration has approved Promacta (eltrombopag) for the treatment of thrombocytopenia in patients with chronic hepatitis C to allow them to initiate and maintain interferon-based therapy. Promacta is a thrombopoietin receptor agonist and has been previously approved for the treatment of thrombocytopenia in patients with chronic immune (idiopathic) thrombocytopenic purpura.

The approval of Promacta for this new indication was granted on the basis of results from 2 phase 3 randomized, double-blind, placebo-controlled, multicenter studies, which collectively enrolled 1521 patients with platelet counts < 75,000/μL. One study utilized peginterferon alfa-2a (Pegasys) plus ribavirin for antiviral treatment and the other study utilized peginterferon alfa-2b (PegIntron) plus ribavirin. Promacta in combination with interferon-based therapy was shown to improve the likelihood that a patient with hepatitis C will achieve a sustained virologic response or viral cure.

The most common adverse reactions in the the clinical trials that compared Promacta versus placebo were the following: anemia (40% vs. 35%), pyrexia (30% vs. 24%), fatigue (28% vs. 23%), headache (21% vs. 20%), nausea (19% vs. 14%), diarrhea (19% vs. 11%), decreased appetite (18% vs. 14%), influenza-like illness (18% vs. 16%), asthenia (16% vs. 13%), insomnia (16 % vs. 15%), cough (15% vs. 12%), pruritus (15% vs. 13%), chills (14% vs. 9%), myalgia (12% vs. 10%), alopecia (10% vs. 6%), and peripheral edema (10% vs. 5%).

The label for Promacta contains a Boxed Warning concerning hepatotoxicity. Use of the drug in combination with interferon and ribavirin in patients with chronic hepatitis C may increase the risk of hepatic decompensation. Patients receiving therapy with Promacta must have regular monitoring of serum liver tests.

Limitations to the use of Promacta in patients with chronic hepatitis C-associated thrombocytopenia exist. Promacta should not be used in an attempt to normalize platelet counts. It should be used only in patients with chronic hepatitis C whose degree of thrombocytopenia prevents the initiation of interferon therapy or limits the ability to maintain optimal interferon-based therapy. The safety and efficacy of Promacta have not been established in combination with direct-acting antiviral agents approved for treatment of chronic hepatitis C genotype 1 infection.