Lusutrombopag可预防慢性肝病患者的血小板减少症

StephenW

Lusutrombopag Prevents Thrombocytopenia in Patients With Chronic Liver Diseases
By Kristine Novak

Lusutrombopag, an oral small molecule agonist of the thrombopoietin receptor, achieves and maintains target platelet count in patients with chronic liver disease and thrombocytopenia undergoing invasive procedures, researchers report in a phase 3, placebo-controlled trial published in the May issue of Clinical Gastroenterology and Hepatology. The drug caused no significant safety concerns.

Proportion of patients who did not require platelet transfusion before the invasive procedure (primary efficacy endpoint). ∗Cochran–Mantel–Haenszel test. CI, confidence interval; LUSU, lusutrombopag; PBO, placebo.

Thrombocytopenia, a deficiency of platelets that increases risk of bleeding, is a common complication of chronic liver diseases. Patients with liver disease and severe thrombocytopenia (platelet count <50,000/μL) have an increased risk of bleeding during surgical procedures and other complications. Of course, there are a number of limitations to this approach, so alternative treatments for thrombocytopenia are needed.

Lusutrombopag has been approved in Japan for treatment of thrombocytopenia in patients with chronic liver diseases scheduled to undergo invasive procedures. The drug activates the thrombopoietin receptor signal transduction pathway to induce platelet production. Lusutrombopag increased the proportion of patients with chronic liver diseases who did not require Preoperative platelet transfusion in a phase 2 trial, compared with placebo.

Hisashi Hidaka et al performed a phase 3 study of lusutrombopag to determine its superiority over placebo in reducing the need for platelet transfusions in thrombocytopenic patients with chronic liver diseases undergoing invasive procedures. In the trial, 98 patients were randomly assigned to groups given once-daily Lusutrombopag (3 mg, n=48) or placebo (n=48) for up to 7 days.

The proportions of patients who did not require preoperative platelet transfusion were 79.2% in the lusutrombopag group and 12.5% ​​in the placebo group. (primary endpoint , see figure). A response (proportion of patients for whom the platelet count reached ≥50,000/μL With an increase of ≥20,000/μL from baseline) was observed in 77.1% of patients in the lusutrombopag group and 6.3% of patients in the placebo group.

In the lusutrombopag group without platelet transfusion, the median platelet count was 50,000/μL or more after 5 days, the mean time to reach the maximum platelet count was 13.4 days, and the number of days (adjusted mean) during which the platelet count was 50,000/μL or more was 21.09 days.

The most frequently reported adverse events were postoperative fever, procedural pain, procedural hypertension, and increased aspartate aminotransferase, reported in both groups.

There were experienced bleeding-related adverse events in the lusutrombopag group (7/48 patients) than that in the placebo group (3/48 patients). One patient in each group had a thrombotic event. Lusutrombopag was effective even in patients with antiplatelet antibodies .

The authors note that the trial excluded patients with splenectomy; any other causes of thrombocytopenia; history of liver transplantation; Child-Pugh class C liver disease, uncontrolled hepatic encephalopathy or ascites despite treatment; malignant tumors other than primary liver cancer; or a history of Portal vein thrombosis. Invasive procedures after day 8, except transcatheter arterial chemoembolization, lipiodolization with anticancer drugs, and transcatheter arterial embolization without lipiodol infusion for marking, were also excluded.

Hidaka et al conclude that lusutrombopag could be an effective substitute for platelet transfusion in patients with chronic liver disease and thrombocytopenia who require invasive procedures.

StephenW

Lusutrombopag可预防慢性肝病患者的血小板减少症
作者：Kristine Novak

Lusutrombopag是血小板生成素受体的口服小分子激动剂，在慢性肝病和血小板减少症患者接受侵入性手术后，可以达到并维持血小板计数，研究人员在5月份临床胃肠病学杂志发表的第3期安慰剂对照试验中报道。肝病。该药物没有引起重大安全问题。

在侵入性手术前不需要血小板输注的患者比例（主要疗效终点）。 * Cochran-Mantel-Haenszel测试。 CI，置信区间; LUSU，lusutrombopag; PBO，安慰剂。

血小板减少症是血小板缺乏，增加出血风险，是慢性肝病的常见并发症。肝病和严重血小板减少症（血小板计数<50,000 /μL）的患者在外科手术和其他并发症中出血的风险增加。当然，这种方法存在许多局限性，因此需要替代治疗血小板减少症。

Lusutrombopag已被日本批准用于治疗计划接受侵入性手术的慢性肝病患者的血小板减少症。该药物激活血小板生成素受体信号转导途径以诱导血小板生成。与安慰剂相比，Lusutrombopag在2期试验中增加了不需要术前血小板输注的慢性肝病患者的比例。

Hisashi Hidaka等人进行了一项关于lusutrombopag的3期研究，以确定其优于安慰剂，以减少慢性肝病患者接受侵入性手术的血小板减少患者血小板输注的需要。在该试验中，98名患者被随机分配到每日一次Lusutrombopag（3 mg，n = 48）或安慰剂（n = 48）最多7天的组。

不需要术前血小板输注的患者比例在lusutrombopag组为79.2％，在安慰剂组为12.5％。 （主要终点，见图）。对于lusutrombopag组中77.1％的患者和安慰剂组中6.3％的患者，观察到响应（血小板计数达到≥50,000/μL的患者比例从基线增加≥20,000/μL）。

在没有血小板输注的lusutrombopag组中，5天后中位血小板计数为50,000 /μL或更多，达到最大血小板计数的平均时间为13.4天，以及血小板计数为的天数（调整后的平均值） 50,000 /μL或更多是21.09天。

两组报告的最常报告的不良事件是术后发热，程序性疼痛，程序性高血压和天冬氨酸氨基转移酶增加。

lusutrombopag组（7/48例患者）出血相关不良事件发生率高于安慰剂组（3/48例患者）。每组中有一名患者发生血栓形成事件。即使在抗血小板抗体患者中，Lusutrombopag也是有效的。

作者指出，该试验排除了脾切除术患者;血小板减少症的任何其他原因;肝移植史; Child-Pugh C级肝病，未经治疗的未控制的肝性脑病或腹水;原发性肝癌以外的恶性肿瘤;或门静脉血栓形成史。第8天后的侵入性手术除了经导管动脉化疗栓塞，使用抗癌药物进行脂质碘化，以及没有使用碘油输注进行标记的经导管动脉栓塞外，也被排除在外。

Hidaka等人得出结论，对于需要侵入性手术的慢性肝病和血小板减少症患者，lusutrombopag可能是血小板输注的有效替代品。