本文由小咖机器人翻译整理

期刊来源：N Engl J Med

原文链接：https://doi.org/10.1056/NEJMoa2308695

摘要内容如下：

背景

持续性溶血性贫血和缺乏口服治疗是阵发性睡眠性血红蛋白尿患者接受抗C5治疗或未接受补体抑制剂治疗的挑战。Iptacopan是一种一流的口服B因子抑制剂，已被证明可以改善这些患者的血红蛋白水平。

方法

在两项3期临床试验中，我们对血红蛋白水平低于10 G/DL的患者进行了为期24周的iptacopan单药治疗评估。在第一组中，抗C5治疗的患者被随机分配为改用iptacopan或继续抗C5治疗。在第二个单组试验中，未接受补体抑制剂治疗且乳酸脱氢酶（LDH）水平超过正常范围上限1.5倍的患者接受iptacopan治疗。第一次试验的两个主要终点是血红蛋白水平从基线增加至少2克/分升和血红蛋白水平至少12克/分升，均未输注红细胞；第二个试验的主要终点是在不输注红细胞的情况下，血红蛋白水平从基线增加至少2克/分升。

结果

在第一个试验中，接受iptacopan治疗的60名患者中，有51名患者的血红蛋白水平较基线至少增加了2克/分升，42名患者的血红蛋白水平至少增加了12克/分升，每名患者均未接受输血；35名接受抗C5治疗的患者均未达到终点水平。在第二个试验中，33名患者中有31名在没有红细胞输注的情况下，血红蛋白水平比基线增加了至少2克/分升。在第一次试验中，62名接受iptacopan治疗的患者中有59名和35名接受抗C5治疗的患者中有14名不需要或不接受输血；在第二个试验中，没有患者需要或接受输血。iptacopan治疗增加了血红蛋白水平，减轻了疲劳，降低了网织红细胞和胆红素水平，并导致平均LDH水平低于正常范围上限的1.5倍。头痛是iptacopan最常见的不良事件。

结论

IPTACOPAN治疗改善了接受抗C5治疗的持续性贫血患者（IPTACOPAN优于抗C5治疗）和未接受补体抑制剂治疗的患者的血液学和临床结果。（由诺华公司资助；APPLY-PNH ClinicalTrials.gov编号，NCT04558918；预约-PNH ClinicalTrials.gov编号，NCT04820530。）

英文原文如下：

Abstracts

BACKGROUND  Persistent hemolytic anemia and a lack of oral treatments are challenges for patients with paroxysmal nocturnal hemoglobinuria who have received anti-C5 therapy or have not received complement inhibitors. Iptacopan, a first-in-class oral factor B inhibitor, has been shown to improve hemoglobin levels in these patients.

METHODS  In two phase 3 trials, we assessed iptacopan monotherapy over a 24-week period in patients with hemoglobin levels of less than 10 g per deciliter. In the first, anti-C5-treated patients were randomly assigned to switch to iptacopan or to continue anti-C5 therapy. In the second, single-group trial, patients who had not received complement inhibitors and who had lactate dehydrogenase (LDH) levels more than 1.5 times the upper limit of the normal range received iptacopan. The two primary end points in the first trial were an increase in the hemoglobin level of at least 2 g per deciliter from baseline and a hemoglobin level of at least 12 g per deciliter, each without red-cell transfusion; the primary end point for the second trial was an increase in hemoglobin level of at least 2 g per deciliter from baseline without red-cell transfusion.

RESULTS  In the first trial, 51 of the 60 patients who received iptacopan had an increase in the hemoglobin level of at least 2 g per deciliter from baseline, and 42 had a hemoglobin level of at least 12 g per deciliter, each without transfusion; none of the 35 anti-C5-treated patients attained the end-point levels. In the second trial, 31 of 33 patients had an increase in the hemoglobin level of at least 2 g per deciliter from baseline without red-cell transfusion. In the first trial, 59 of the 62 patients who received iptacopan and 14 of the 35 anti-C5-treated patients did not require or receive transfusion; in the second trial, no patients required or received transfusion. Treatment with iptacopan increased hemoglobin levels, reduced fatigue, reduced reticulocyte and bilirubin levels, and resulted in mean LDH levels that were less than 1.5 times the upper limit of the normal range. Headache was the most frequent adverse event with iptacopan.

CONCLUSIONS  Iptacopan treatment improved hematologic and clinical outcomes in anti-C5-treated patients with persistent anemia - in whom iptacopan showed superiority to anti-C5 therapy - and in patients who had not received complement inhibitors. (Funded by Novartis; APPLY-PNH ClinicalTrials.gov number, NCT04558918; APPOINT-PNH ClinicalTrials.gov number, NCT04820530.).

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