Yang Renchi, Li Junmin, Jin Jie, Huang Meijuan, Yu Ziqiang, Xu Xiaojun, Zhang Xiaohui, Hou Ming
Institute of Haematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences, Tianjin, China.
Department of Haematology, Ruijin Hospital affiliated to Shanghai Jiao Tong University, Shanghai, China.
Br J Haematol. 2017 Jan;176(1):101-110. doi: 10.1111/bjh.14380. Epub 2016 Oct 13.
Eltrombopag, a thrombopoietin receptor agonist, raises platelet counts and reduces bleeding in patients with immune thrombocytopenia (ITP). In Chinese patients, eltrombopag was evaluated at an initial dose of 25 mg, vs. 50 mg for non-Asians, because the plasma exposure of eltrombopag is higher in East Asians. A multicentre, double-blind, randomised, placebo-controlled, 8-week, phase III study enrolled 155 patients with chronic, previously treated ITP. Dosage could be adjusted (25-75 mg/day) to maintain platelet counts 50-250 × 10 /l. The primary efficacy endpoint was the proportion of patients with a platelet count ≥50 × 10 /l after Day 42. Pharmacokinetics and pharmacodynamics of eltrombopag were analysed in an open-label extension. After Day 42, 57·7% of eltrombopag-treated and 6·0% of placebo-treated patients achieved platelet counts ≥50 × 10 /l. Odds of achieving a platelet count ≥50 × 10 /l were 26·08 times greater with eltrombopag than placebo (P < 0·001). Compared with placebo, time to response and duration of response were better with eltrombopag (P < 0·001) and the odds of any bleeding were reduced by 72% (P = 0·001). Tolerability, pharmacokinetics, and pharmacokinetics/pharmacodynamics were similar to previous findings in East Asian patients. In conclusion, in Chinese patients with chronic ITP, eltrombopag 25 mg once daily, elevated platelet counts to a safe range and reduced bleeding.
艾曲泊帕是一种血小板生成素受体激动剂，可提高免疫性血小板减少症（ITP）患者的血小板计数并减少出血。在中国患者中，艾曲泊帕的初始剂量评估为25mg，而非亚洲患者为50mg，因为艾曲泊帕在东亚人群中的血浆暴露量更高。一项多中心、双盲、随机、安慰剂对照、为期8周的III期研究纳入了155例曾接受过治疗的慢性ITP患者。剂量可进行调整（25 - 75mg/天），以维持血小板计数在50 - 250×10⁹/L。主要疗效终点是第42天后血小板计数≥50×10⁹/L的患者比例。在一项开放标签扩展研究中分析了艾曲泊帕的药代动力学和药效学。第42天后，接受艾曲泊帕治疗的患者中有57.7%达到血小板计数≥50×10⁹/L，而接受安慰剂治疗的患者中这一比例为6.0%。艾曲泊帕组达到血小板计数≥50×10⁹/L的几率是安慰剂组的26.08倍（P < 0.001）。与安慰剂相比，艾曲泊帕的起效时间和反应持续时间更佳（P < 0.001），且任何出血的几率降低了72%（P = 0.001）。耐受性、药代动力学以及药代动力学/药效学与之前在东亚患者中的研究结果相似。总之，对于中国慢性ITP患者，每日一次服用25mg艾曲泊帕可将血小板计数提高到安全范围并减少出血。
