garadacimab可诱发遗传性血管性水肿的无发作状态，与基线特征无关

IF 5.8 2区医学 Q1 ALLERGY

Annals of Allergy Asthma & Immunology Pub Date : 2024-10-25 DOI:10.1016/j.anai.2024.08.127

J. Anderson , J. Bernstein , W. Yang , K. Kohga , K. Sitz , I. Jacobs , H. Feuersenger , R. Tachdjian

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引用次数: 0

摘要

导言遗传性血管性水肿（HAE）发作反复、难以预测、使人衰弱并可能危及生命。现行指南规定，HAE 的治疗目标是完全控制病情和恢复正常生活。加拉达西单抗是一种全人源、每月一次的抗活化因子 XII 单克隆抗体，在关键的三期（VANGUARD）研究中被评估为 HAE 长期预防药物，62% 的加拉达西单抗治疗患者不再发作（所有接受安慰剂治疗的患者均发作）。在为期 6 个月的随机关键性 3 期（VANGUARD）研究中，患者每月一次皮下注射加拉达西单抗 200 毫克（39 人）或安慰剂（25 人）。比较了接受加拉达单抗治疗的无发作患者（24人）与发作次数≥1次的患者（15人）的不同患者特征：年龄、体重指数、确诊年龄、磨合期内每月发作次数、磨合期内轻度/中度/重度发作率以及磨合期内中度/重度合并发作率。结果所有评估特征对无发作状态的预测能力均较低（尤登指数范围为 0.18-0.39；敏感性为 25.0-79.2%；特异性为 53.3-93.3%；表）。结论在关键的 3 期（VANGUARD）研究中，HAE 患者使用加拉达西单抗后可达到无发作状态，与评估的患者基线特征无关。无论基线特征如何，HAE患者都有可能通过使用加拉达单抗达到无发作状态。

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GARADACIMAB ELICITS ATTACK-FREE STATUS IN HEREDITARY ANGIOEDEMA INDEPENDENT OF BASELINE CHARACTERISTICS

Introduction

Hereditary angioedema (HAE) attacks are recurrent, unpredictable, debilitating, and potentially life-threatening. Current guidelines state HAE treatment goals are complete disease control and normalization of life. Garadacimab, a fully human, once-monthly, anti-activated factor XII monoclonal antibody, was evaluated as HAE long-term prophylaxis in the pivotal Phase 3 (VANGUARD) study, and 62% of garadacimab-treated patients were attack-free (all patients receiving placebo experienced attacks). This post hoc analysis evaluated potential association between baseline patient characteristics and attack-free status.

Methods

In the 6-month, randomized, pivotal Phase 3 (VANGUARD) study, patients received garadacimab 200 mg subcutaneously (n=39) or placebo (n=25) once monthly. Patients treated with garadacimab who were attack-free (n=24) vs those with ≥1 attack (n=15) were compared across patient characteristics: age, body mass index, age at diagnosis, attacks per month during the run-in period, rate of mild/moderate/severe attacks during the run-in period, and combined rate of moderate/severe attacks during the run-in period. Youden-index was calculated for each characteristic, whereby 0 indicates no predictive ability for attack-free status and 1 indicates perfect predictive ability.

Results

All evaluated characteristics had low predictive ability for attack-free status (Youden-index range 0.18–0.39; sensitivity 25.0–79.2%; specificity 53.3–93.3%; Table). Attacks per month during the run-in period had the highest predictive power, but still had a low ability to predict attack-free status (Youden-index 0.39).

Conclusion

In the pivotal Phase 3 (VANGUARD) study, patients with HAE achieved attack-free status with garadacimab independently of evaluated baseline patient characteristics. Regardless of baseline characteristics, patients with HAE have the potential to achieve attack-free status with garadacimab.

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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.