在阵发性夜间血红蛋白尿的成人患者中,接受佩西可普兰治疗的有效性和安全性维持长达3年。

IF 4 3区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL
Carlos de Castro, Richard J Kelly, Morag Griffin, Christopher J Patriquin, Brian Mulherin, Britta Höchsmann, Veena Selvaratnam, Raymond Siu Ming Wong, Peter Hillmen, Regina Horneff, Uchendu O Uchendu, Yiwei Zhang, Elena Surova, Johan Szamosi, Regis Peffault de Latour
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引用次数: 0

摘要

PEGASUS (NCT03500549)和PRINCE (NCT04085601)的3期研究中,pecetacoplan是首个治疗突发性夜间血红蛋白尿(PNH)的C3和C3b抑制剂,分别在C5抑制剂经验和新手患者中显示出有效性和安全性。这项对PEGASUS、PRINCE及其后续开放标签扩展研究(NCT03531255)的综合分析评估了pegcetacoplan的长期疗效和安全性。方法:通过测量血红蛋白、乳酸脱氢酶(LDH)、绝对网状红细胞计数(ARC)、间接胆红素和慢性疾病治疗功能评估(FACIT)-疲劳评分,从pegcetacoplan开始到2.5年(PRINCE)和3年(PEGASUS),对疗效进行评估。在pegcetacoplan单药治疗期间,对输血避免和安全性进行了评估。在PRINCE和PEGASUS的133名患者中,114名患者参加了延期试验。大多数患者(PRINCE, 81.1%;PEGASUS(75.0%)在试验开始时依赖输血,基线血红蛋白低于正常水平。结果:佩头孢柯酮在4周内显著、快速地改善了各项疗效指标,稳定在接近(血红蛋白、FACIT-Fatigue)或(LDH、ARC、间接胆红素)正常范围内长达3年;PRINCE的年避免输血率为79.5 ~ 86.4%,PEGASUS的年避免输血率为71.2 ~ 79.2%。3年来没有发现新的安全隐患。73例(55.3%)患者报告了严重不良事件,6例(4.5%)患者被认为与培西可平相关。大多数注射部位的反应是轻微的,其发生率随着时间的推移而降低。发生5例(3.8%)死亡(无一例被认为与佩西可平相关);37例(28.0%)患者出现临床显著且实验室证实的突破性溶血;3例(2.3%)患者发生4例血栓形成事件;未有脑膜炎个案报告。结论:Pegcetacoplan在PNH患者中,无论是否接受过C5抑制剂治疗,其疗效和安全性持续长达3年,验证了这种近端补体抑制剂的长期良好临床特征。试验注册:ClinicalTrials.gov NCT03500549 (PEGASUS)、NCT04085601 (PRINCE)和NCT03531255 (307 OLE)。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Efficacy and Safety Maintained up to 3 Years in Adults with Paroxysmal Nocturnal Hemoglobinuria Receiving Pegcetacoplan.

Introduction: Pegcetacoplan, the first C3 and C3b inhibitor for paroxysmal nocturnal hemoglobinuria (PNH), demonstrated efficacy and safety in C5 inhibitor-experienced and -naive patients in the phase 3 studies PEGASUS (NCT03500549) and PRINCE (NCT04085601), respectively. This integrated analysis of PEGASUS, PRINCE, and their subsequent open-label extension study (NCT03531255) evaluated pegcetacoplan long-term efficacy and safety.

Methods: Efficacy was assessed from pegcetacoplan initiation through 2.5 years (PRINCE) and 3 years (PEGASUS) by measuring hemoglobin, lactate dehydrogenase (LDH), absolute reticulocyte count (ARC), indirect bilirubin, and Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue scores. Transfusion avoidance and safety were assessed during pegcetacoplan monotherapy. Of 133 patients in PRINCE and PEGASUS, 114 enrolled in the extension. Most patients (PRINCE, 81.1%; PEGASUS, 75.0%) were transfusion dependent at trial entry and baseline hemoglobin was below normal.

Results: Pegcetacoplan markedly and rapidly (within 4 weeks) improved all efficacy measures, which stabilized close to (hemoglobin, FACIT-Fatigue) or within (LDH, ARC, indirect bilirubin) normal range for up to 3 years; annual transfusion avoidance rates were 79.5-86.4% in PRINCE and 71.2-79.2% in PEGASUS. No new safety concerns were identified over 3 years. Serious adverse events were reported in 73 (55.3%) patients, deemed pegcetacoplan related in 6 (4.5%) patients. Most injection site reactions were mild, and their incidence decreased over time. Five (3.8%) deaths occurred (none deemed pegcetacoplan related); 37 (28.0%) patients experienced clinically significant and laboratory-confirmed breakthrough hemolysis; 4 thrombotic events occurred in 3 (2.3%) patients; no meningitis cases were reported.

Conclusion: Pegcetacoplan efficacy and safety was sustained for up to 3 years in patients with PNH, with or without prior C5 inhibitor treatment, verifying the long-term favorable clinical profile of this proximal complement inhibitor.

Trial registration: ClinicalTrials.gov NCT03500549 (PEGASUS), NCT04085601 (PRINCE), and NCT03531255 (307 OLE).

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来源期刊
Advances in Therapy
Advances in Therapy 医学-药学
CiteScore
7.20
自引率
2.60%
发文量
353
审稿时长
6-12 weeks
期刊介绍: Advances in Therapy is an international, peer reviewed, rapid-publication (peer review in 2 weeks, published 3–4 weeks from acceptance) journal dedicated to the publication of high-quality clinical (all phases), observational, real-world, and health outcomes research around the discovery, development, and use of therapeutics and interventions (including devices) across all therapeutic areas. Studies relating to diagnostics and diagnosis, pharmacoeconomics, public health, epidemiology, quality of life, and patient care, management, and education are also encouraged. The journal is of interest to a broad audience of healthcare professionals and publishes original research, reviews, communications and letters. The journal is read by a global audience and receives submissions from all over the world. Advances in Therapy will consider all scientifically sound research be it positive, confirmatory or negative data. Submissions are welcomed whether they relate to an international and/or a country-specific audience, something that is crucially important when researchers are trying to target more specific patient populations. This inclusive approach allows the journal to assist in the dissemination of all scientifically and ethically sound research.
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