CHARACTERIZATION OF INJECTION SITE-RELATED ADVERSE EVENTS WITH GARADACIMAB IN PATIENTS WITH HEREDITARY ANGIOEDEMA

IF 5.8 2区医学 Q1 ALLERGY

Annals of Allergy Asthma & Immunology Pub Date : 2024-10-25 DOI:10.1016/j.anai.2024.08.121

J. Jacobs , M. Manning , A. Reshef , K. Yamagami , H. Shetty , J. Lawo , M. Pollen , F. Hsu

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引用次数: 0

Abstract

Introduction

Hereditary angioedema (HAE) is characterized by unpredictable, recurrent, and potentially life-threatening attacks. Garadacimab, a subcutaneous, once-monthly, fully human anti-activated factor XII monoclonal antibody in development for long-term prophylaxis (LTP), has demonstrated early and durable efficacy and favorable safety profile, and allowed most patients to achieve the HAE treatment goal of total disease control in clinical studies. Approved LTPs have demonstrated treatment-related injection-site reactions (e.g., pain, erythema, bruising). Patients have indicated a preference for new LTPs that reduce treatment burden. We characterize injection-site adverse events from the garadacimab Phase 3 clinical program.

Methods

Treatment-related injection-site reaction (ISR) data were analyzed from the pivotal Phase 3 (VANGUARD) and Phase 3 open-label extension (OLE) studies. Patient proportions, event numbers (E), and annualized rate (RY) data for ISRs were reported by study treatment group and preferred term within those groups.

Results

In the pivotal Phase 3 (VANGUARD) study (median garadacimab exposure: 5.98 months), 2/39 of garadacimab-treated patients (5.1%; E=3, RY=0.154) and 2/25 placebo-receiving patients (8.0%; E=2, RY=0.177) reported ISRs. Garadacimab-related ISRs were erythema, bruising, and pruritus (2.6% each; E=1, RY=0.051). Both placebo-related ISRs were erythema. In the Phase 3 OLE study (median garadacimab exposure: 13.8 months), 14/159 garadacimab-treated patients (8.8%; E=36, RY=0.195) reported ISRs – erythema (6.8%; E=14, RY=0.075), pruritus (2.5%; E=12, RY=0.065) and irritation (0.6%; E=1, RY=0.005; moderate, discontinuation at Month 6 upon patient decision).

Conclusion

In garadacimab Phase 3 studies, incidence of ISRs such as erythema, bruising and pruritus was low. The favorable injection-site tolerability with garadacimab may help reduce treatment burden during HAE LTP treatment.

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遗传性血管性水肿患者使用加拉达西单抗发生的注射部位相关不良事件的特征描述

导言遗传性血管性水肿（HAE）的特点是发作难以预测、反复发作并可能危及生命。加拉地单抗是一种皮下注射、每月一次的全人源抗活化因子 XII 单克隆抗体，目前正在开发用于长期预防（LTP），已证明具有早期、持久的疗效和良好的安全性，并使大多数患者在临床研究中实现了完全控制疾病的 HAE 治疗目标。已获批准的 LTPs 出现了与治疗相关的注射部位反应（如疼痛、红斑、瘀伤）。患者表示更青睐能减轻治疗负担的新型 LTP。我们分析了加拉达西单抗 3 期临床项目中注射部位不良事件的特征。方法分析了关键性 3 期（VANGUARD）和 3 期开放标签扩展（OLE）研究中与治疗相关的注射部位反应（ISR）数据。结果在关键的3期（VANGUARD）研究中（中位加拉达西单抗暴露期：5.98个月），2/39的加拉达西单抗治疗患者（5.1%；E=3，RY=0.154）和2/25的安慰剂接受患者（8.0%；E=2，RY=0.177）报告了ISR。加拉地单抗相关的 ISR 为红斑、瘀伤和瘙痒（各占 2.6%；E=1，RY=0.051）。安慰剂相关的 ISR 均为红斑。在 3 期 OLE 研究中（中位加拉达西单抗暴露时间：13.8 个月），14/159 名加拉达西单抗治疗患者（8.8%；E=36，RY=0.195）报告了 ISRs--红斑（6.8%；E=14，RY=0.075）、瘙痒（2.5%；E=12，RY=0.结论在加拉地单抗 3 期研究中，红斑、瘀斑和瘙痒等 ISR 的发生率较低。加拉单抗良好的注射部位耐受性可能有助于减轻HAE LTP治疗期间的治疗负担。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Annals of Allergy Asthma & Immunology 医学-过敏

CiteScore

6.50

自引率

6.80%

发文量

437

审稿时长

33 days

期刊介绍： Annals of Allergy, Asthma & Immunology is a scholarly medical journal published monthly by the American College of Allergy, Asthma & Immunology. The purpose of Annals is to serve as an objective evidence-based forum for the allergy/immunology specialist to keep up to date on current clinical science (both research and practice-based) in the fields of allergy, asthma, and immunology. The emphasis of the journal will be to provide clinical and research information that is readily applicable to both the clinician and the researcher. Each issue of the Annals shall also provide opportunities to participate in accredited continuing medical education activities to enhance overall clinical proficiency.