Al-Samkari Hanny, Nagalla Srikanth
Division of Hematology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Division of Benign Hematology, Miami Cancer Institute, Miami, FL, USA.
Platelets. 2022 Feb 17;33(2):257-264. doi: 10.1080/09537104.2021.1881952. Epub 2021 Feb 14.
Avatrombopag is an oral thrombopoietin receptor agonist approved for chronic immune thrombocytopenia (ITP). This is a post hoc analysis of the pivotal phase III study (NCT01438840) evaluating additional endpoints not previously described. Thirty-two ITP patients were randomized to avatrombopag and 17 were randomized to placebo during a 26-week core study period (with 21 study visits), followed by an open-label extension period, in which all patients received avatrombopag for varying lengths of time. In this analysis, we evaluated previously unreported response rates at the study visit level, durability of response, and reduction in corticosteroid use with avatrombopag treatment. In the core study, more avatrombopag-treated patients achieved either response (Plt ≥50 000/µL) or complete response (Plt ≥100 000/µL) than placebo-treated patients by day 8 (65.6% vs. 0%; < .0001 for response; 37.5% vs. 0%; < .0001 for complete response), day 28 (84.4% vs. 0%; < .0001 for response; 71.9% vs. 0%; < .0001 for complete response), and month 6 (87.5% vs. 5.9%; < .0001 for response; 81.3% vs. 5.9%; < .0001 for complete response). Durable responders from the core study achieved response and complete response at 96.1% and 60.1% of extension phase visits, respectively. Durable clinically relevant response (Plt ≥30 000/µL for 6 of the final 8 weeks of the core study) occurred in 64.0% of avatrombopag-treated patients versus 0% of placebo-treated patients. More than half (57.1%) of patients on chronic corticosteroids reduced or discontinued corticosteroids. In conclusion, avatrombopag enabled most patients with ITP to achieve clinically meaningful and durable platelet count improvements.
阿伐曲泊帕是一种口服血小板生成素受体激动剂，已被批准用于治疗慢性免疫性血小板减少症（ITP）。这是一项对关键III期研究（NCT01438840）的事后分析，评估了先前未描述的额外终点。在为期26周的核心研究期（共21次研究访视）中，32例ITP患者被随机分配至阿伐曲泊帕组，17例被随机分配至安慰剂组，随后进入开放标签延长期，在此期间所有患者接受不同时长的阿伐曲泊帕治疗。在本分析中，我们评估了研究访视水平上先前未报告的缓解率、缓解的持久性以及阿伐曲泊帕治疗对皮质类固醇使用的减少情况。在核心研究中，到第8天，接受阿伐曲泊帕治疗的患者实现反应（血小板计数≥50 000/µL）或完全反应（血小板计数≥100 000/µL）的比例高于接受安慰剂治疗的患者（反应率：65.6% vs. 0%；P<0.0001；完全反应率：37.5% vs. 0%；P<0.0001），第28天（反应率：84.4% vs. 0%；P<0.0001；完全反应率：71.9% vs. 0%；P<0.0001）以及第6个月（反应率：87.5% vs. 5.9%；P<0.0001；完全反应率：81.3% vs. 5.9%；P<0.0001）。核心研究中的持久缓解者在延长期访视中实现反应和完全反应的比例分别为96.1%和60.1%。持久的临床相关反应（在核心研究的最后8周中有6周血小板计数≥30 000/µL）在接受阿伐曲泊帕治疗的患者中发生率为64.0%，而接受安慰剂治疗的患者中为0%。超过一半（57.1%）接受慢性皮质类固醇治疗的患者减少或停用了皮质类固醇。总之，阿伐曲泊帕使大多数ITP患者实现了具有临床意义且持久的血小板计数改善。
