Abteilung Innere Medizin & Gastroenterologie, mit Zentraler Aufnahme & Erstversorgung, Klinikum Klagenfurt am Wörthersee, Klagenfurt, Austria.
Department of Infectious Diseases and Hepatology, Wroclaw Medical University, Wroclaw, Poland.
Hepatology. 2019 Oct;70(4):1336-1348. doi: 10.1002/hep.30561. Epub 2019 Mar 15.
Thrombocytopenia may be associated with increased bleeding risk impacting timing and outcome of invasive procedures in patients with chronic liver disease (CLD). Lusutrombopag, a small-molecule, thrombopoietin (TPO) receptor agonist, was evaluated as a treatment to raise platelet counts (PCs) in patients with thrombocytopenia and CLD undergoing invasive procedures. L-PLUS 2 was a global, phase 3, randomized, double-blind, placebo-controlled study. Adults with CLD and baseline PCs < 50 × 10 /L were randomized to receive once-daily lusutrombopag 3 mg or placebo ≤ 7 days before an invasive procedure scheduled 2-7 days after the last dose. The primary endpoint was avoidance of preprocedure platelet transfusion and avoidance of rescue therapy for bleeding. A key secondary endpoint was number of days PCs were ≥ 50 × 10 /L throughout the study. Safety analysis was performed on patients who received at least one dose of study drug. This study occurred between June 15, 2015, and April 19, 2017, with a total of 215 randomized patients (lusutrombopag, 108; placebo, 107); 64.8% (70/108) of patients in the lusutrombopag group versus 29.0% (31/107) in the placebo group met the primary endpoint (P < 0.0001; difference of proportion 95% confidence interval [CI], 36.7 [24.9, 48.5]). The median duration of PCs ≥ 50 × 10 /L was 19.2 days with lusutrombopag (without platelet transfusion) compared with 0.0 in the placebo group (with platelet transfusion) (P = 0.0001). Most adverse events were mild or moderate in severity, and rates were similar in the lusutrombopag and placebo groups (47.7% and 48.6%, respectively). Conclusion: Lusutrombopag was superior to placebo for reducing the need for platelet transfusions and achieved durable PC response in patients with thrombocytopenia and CLD undergoing invasive procedures, with a safety profile similar to placebo.
血小板减少症可能与增加出血风险有关，影响慢性肝病 (CLD) 患者侵入性操作的时机和结果。Lusutrombopag 是一种小分子、血小板生成素 (TPO) 受体激动剂，已被评估用于治疗血小板减少症和 CLD 患者侵入性操作前升高血小板计数 (PC)。L-PLUS 2 是一项全球性的 3 期随机、双盲、安慰剂对照研究。基线 PC<50×10 /L 的 CLD 成年患者在预定的侵入性操作前 2-7 天内最后一次给药后≤7 天内随机接受 lusutrombopag 3mg 或安慰剂每日一次治疗。主要终点是避免术前血小板输注和避免出血的抢救治疗。主要次要终点是整个研究期间 PC≥50×10 /L 的天数。安全性分析在至少接受一剂研究药物的患者中进行。该研究于 2015 年 6 月 15 日至 2017 年 4 月 19 日进行，共有 215 名随机患者（lusutrombopag 组 108 名，安慰剂组 107 名）；lusutrombopag 组中 64.8%（70/108）的患者与安慰剂组中 29.0%（31/107）的患者达到主要终点（P<0.0001；比例差异 95%置信区间[CI]，36.7[24.9, 48.5]）。lusutrombopag 组的 PC≥50×10 /L 中位持续时间为 19.2 天（无血小板输注），安慰剂组为 0.0 天（血小板输注）（P=0.0001）。大多数不良事件的严重程度为轻度或中度，lusutrombopag 组和安慰剂组的发生率相似（分别为 47.7%和 48.6%）。结论：在接受侵入性操作的血小板减少症和 CLD 患者中，与安慰剂相比，lusutrombopag 可降低血小板输注的需求，并实现持久的 PC 反应，安全性与安慰剂相似。
