Chinese University of Hong Kong, Shatin, NT, Hong Kong SAR, China.
Lancet. 2011 Jan 29;377(9763):393-402. doi: 10.1016/S0140-6736(10)60959-2. Epub 2010 Aug 23.
Eltrombopag is an oral thrombopoietin receptor agonist for the treatment of thrombocytopenia. We aimed to compare the response to once daily eltrombopag versus placebo in patients with chronic immune thrombocytopenia during a 6-month period.
We undertook a phase 3, double-blind, placebo-controlled study in adults with previously treated immune thrombocytopenia of more than 6 months' duration who had baseline platelet counts lower than 30,000 per μL. Patients were randomly allocated (in a 2:1 ratio) treatment with local standard of care plus 50 mg eltrombopag or matching placebo once daily for 6 months. Randomisation was done centrally with a computer-generated randomisation schedule and was stratified by baseline platelet count (≤ 15,000 per μL), use of treatment for immune thrombocytopenia, and splenectomy status. Patients, investigators, and those assessing data were masked to allocation. Dose modifications were made on the basis of platelet response. Patients were assessed for response to treatment (defined as a platelet count of 50,000-400,000 per μL) weekly during the first 6 weeks and at least once every 4 weeks thereafter; the primary endpoint was the odds of response to eltrombopag versus placebo. Analysis was by intention to treat. This study is registered at ClinicalTrials.gov, number NCT00370331.
Between Nov 22, 2006, and July 31, 2007, 197 patients were randomly allocated to treatment groups and were included in the intention-to-treat analysis (135 eltrombopag, 62 placebo). 106 (79%) patients in the eltrombopag group responded to treatment at least once during the study, compared with 17 (28%) patients in the placebo group. The odds of responding were greater in patients in the eltrombopag group compared with those in the placebo group throughout the 6-month treatment period (odds ratio 8·2, 99% CI 3·59-18·73; p<0·0001). 37 (59%) patients receiving eltrombopag reduced concomitant treatment versus ten (32%) patients receiving placebo (p=0·016). 24 (18%) patients receiving eltrombopag needed rescue treatment compared with 25 (40%) patients receiving placebo (p=0·001). Three (2%) patients receiving eltrombopag had thromboembolic events compared with none in patients on placebo. Nine (7%) eltrombopag-treated patients and two (3%) in the placebo group had mild increases in alanine aminotransferase concentration, and five (4%) eltrombopag-treated patients (vs none allocated to placebo) had increases in total bilirubin. Four (7%) patients taking placebo had serious bleeding events, compared with one (<1%) patient treated with eltrombopag.
Eltrombopag is effective for management of chronic immune thrombocytopenia, and could be particularly beneficial for patients who have not responded to splenectomy or previous treatment. These benefits should be balanced with the potential risks associated with eltrombopag treatment.
GlaxoSmithKline.
艾曲波帕是一种用于治疗血小板减少症的口服血小板生成素受体激动剂。我们旨在比较 6 个月期间，每日一次艾曲波帕与安慰剂在慢性免疫性血小板减少症患者中的反应。
我们进行了一项 3 期、双盲、安慰剂对照研究，纳入了先前接受治疗的免疫性血小板减少症超过 6 个月且基线血小板计数低于 30,000/μL 的成年人患者。患者被随机分配（2:1 比例）接受局部标准治疗加 50mg 艾曲波帕或匹配的安慰剂，每日一次，持续 6 个月。随机化通过中央计算机生成的随机化方案进行，按基线血小板计数（≤15,000/μL）、免疫性血小板减少症治疗的使用情况和脾切除术状态进行分层。患者、研究者和评估数据的人员对分配情况进行了盲法。根据血小板反应进行剂量调整。在最初的 6 周内每周评估治疗反应（定义为血小板计数为 50,000-400,000/μL），此后至少每 4 周评估一次；主要终点是艾曲波帕与安慰剂相比的反应几率。分析按意向治疗进行。本研究在 ClinicalTrials.gov 注册，编号为 NCT00370331。
在 2006 年 11 月 22 日至 2007 年 7 月 31 日期间，197 名患者被随机分配到治疗组，并纳入意向治疗分析（135 名接受艾曲波帕，62 名接受安慰剂）。在研究期间，艾曲波帕组中有 106 名（79%）患者至少有一次治疗反应，而安慰剂组中有 17 名（28%）患者。在整个 6 个月的治疗期间，艾曲波帕组的反应几率大于安慰剂组（比值比 8.2，99%CI 3.59-18.73；p<0.0001）。与接受安慰剂的患者相比，接受艾曲波帕治疗的 37 名（59%）患者减少了同时治疗（p=0.016）。与接受安慰剂的患者相比，接受艾曲波帕治疗的 24 名（18%）患者需要挽救治疗（p=0.001）。与接受安慰剂的患者相比，接受艾曲波帕治疗的 3 名（2%）患者发生血栓栓塞事件，而接受安慰剂的患者无此类事件。接受艾曲波帕治疗的 9 名（7%）患者和安慰剂组的 2 名（3%）患者丙氨酸氨基转移酶浓度轻度升高，接受艾曲波帕治疗的 5 名（4%）患者（与安慰剂组相比）总胆红素升高。接受安慰剂的 4 名（7%）患者发生严重出血事件，而接受艾曲波帕治疗的患者中仅有 1 名（<1%）。
艾曲波帕对慢性免疫性血小板减少症的治疗有效，对于那些对脾切除术或先前治疗没有反应的患者可能特别有益。这些益处应与艾曲波帕治疗相关的潜在风险相平衡。
葛兰素史克。
