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期刊来源：N Engl J Med

原文链接：https://doi.org/10.1056/NEJMoa2308809

摘要内容如下：

背景

真性红细胞增多症是一种以红细胞增多为特征的慢性骨髓增殖性肿瘤。鲁斯菲肽（Rusfertide）是一种主要铁调节激素铁调素（Hepcidin）的可注射模拟肽，它限制了红细胞生成过程中铁的可用性。拉弗肽治疗静脉切开术依赖性真性红细胞增多症患者的安全性和有效性尚不清楚。

方法

在国际2期REVIVE试验的第1部分中，我们招募患者进行为期28周的鲁斯非肽剂量探索评估。第2部分是一个双盲、随机的停药期，我们将患者按1:1的比例分配接受12周的拉非肽或安慰剂治疗。主要疗效终点是反应，定义为血细胞比容控制、未进行放血和完成第2部分期间的试验方案。患者报告的结果通过改良骨髓增殖性肿瘤症状评估表（MPN-SAF）患者日记进行评估（评分范围为0至10，评分越高表示症状越严重）。

结果

试验的第1部分招募了70名患者，在第2部分中，59名患者被分配接受鲁斯菲肽（30名患者）或安慰剂（29名患者）。在第一次给予鲁斯菲肽之前的28周内，每年静脉切开术的估计平均（±SD）次数为8.7±2.9，在第1部分期间为0.6±1.0（估计差异，每年8.1次静脉切开术）。在第1部分期间，平均最大血细胞比容为44.5±2.2%，而在首次给予鲁斯菲肽之前的28周期间，平均最大血细胞比容为50.0±5.8%。在第2部分中，观察到60%接受拉菲肽治疗的患者有反应，而接受安慰剂治疗的患者只有17%有反应（P=0.00 2）。在基线和第1部分结束之间，在基线时有中度或重度症状的患者中，鲁斯菲肽治疗与MPN-SAF的个体症状评分下降相关。在第1部分和第2部分中，13%的患者发生了3级不良事件，没有患者发生4级或5级不良事件。严重程度为1级或2级的注射部位反应很常见。

结论

在真性红细胞增多症患者中，在28周的剂量探索期间，鲁斯菲肽治疗与平均血细胞比容低于45%相关，并且在12周的随机停药期内，鲁斯菲肽治疗的反应患者的百分比高于安慰剂。（由主角治疗公司资助；Revive ClinicalTrials.gov，NCT04057040）。

英文原文如下：

Abstracts

BACKGROUND  Polycythemia vera is a chronic myeloproliferative neoplasm characterized by erythrocytosis. Rusfertide, an injectable peptide mimetic of the master iron regulatory hormone hepcidin, restricts the availability of iron for erythropoiesis. The safety and efficacy of rusfertide in patients with phlebotomy-dependent polycythemia vera are unknown.

METHODS  In part 1 of the international, phase 2 REVIVE trial, we enrolled patients in a 28-week dose-finding assessment of rusfertide. Part 2 was a double-blind, randomized withdrawal period in which we assigned patients, in a 1:1 ratio, to receive rusfertide or placebo for 12 weeks. The primary efficacy end point was a response, defined by hematocrit control, absence of phlebotomy, and completion of the trial regimen during part 2. Patient-reported outcomes were assessed by means of the modified Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF) patient diary (scores range from 0 to 10, with higher scores indicating greater severity of symptoms).

RESULTS  Seventy patients were enrolled in part 1 of the trial, and 59 were assigned to receive rusfertide (30 patients) or placebo (29 patients) in part 2. The estimated mean (±SD) number of phlebotomies per year was 8.7±2.9 during the 28 weeks before the first dose of rusfertide and 0.6±1.0 during part 1 (estimated difference, 8.1 phlebotomies per year). The mean maximum hematocrit was 44.5±2.2% during part 1 as compared with 50.0±5.8% during the 28 weeks before the first dose of rusfertide. During part 2, a response was observed in 60% of the patients who received rusfertide as compared with 17% of those who received placebo (P = 0.002). Between baseline and the end of part 1, rusfertide treatment was associated with a decrease in individual symptom scores on the MPN-SAF in patients with moderate or severe symptoms at baseline. During parts 1 and 2, grade 3 adverse events occurred in 13% of the patients, and none of the patients had a grade 4 or 5 event. Injection-site reactions of grade 1 or 2 in severity were common.

CONCLUSIONS  In patients with polycythemia vera, rusfertide treatment was associated with a mean hematocrit of less than 45% during the 28-week dose-finding period, and the percentage of patients with a response during the 12-week randomized withdrawal period was greater with rusfertide than with placebo. (Funded by Protagonist Therapeutics; REVIVE ClinicalTrials.gov number, NCT04057040.).

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