每日一次贝曲司他治疗遗传性血管性水肿患者的长期安全性和有效性：APeX-S最终结果。

IF 4.7 2区医学 Q1 ALLERGY

Annals of Allergy Asthma & Immunology Pub Date : 2025-09-01 DOI:10.1016/j.anai.2025.06.004

Henriette Farkas MD , Jonny G. Peter MD , Marcin Stobiecki MD , John Anderson MD , Emel Aygören-Pürsün MD , David Hagin MD , Miloš Jeseňák MD , Aharon Kessel MD , Sorena Kiani-Alikhan MD , Tamar Kinaciyan MD , Michael Manning MD , Avner Reshef MD , Adrian Wu MD , Heather A. Iocca PhD , Douglas T. Johnston MD , Lindsey Noble PhD , Dianne Tomita PhD , Aleena Banerji MD

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引用次数: 0

摘要

背景：贝罗曲司他是一种每日一次的口服药物，用于预防≥12岁患者的遗传性血管性水肿（HAE）发作。目的：APeX-S旨在评估贝罗曲司他治疗C1抑制剂缺乏所致HAE患者的长期安全性和有效性。方法：APeX-S是一项全球开放标签2期研究（NCT03472040），评估贝曲司他150和110 mg在美国长达96周，在其他地区长达240周。主要目标是长期安全性和耐受性；次要目标包括贝曲司他的疗效和对生活质量的影响。通过治疗不良事件（teae）和实验室分析来评估安全性。通过HAE发作次数和发生率、反应持续时间以及出现血管性水肿症状的天数和比例来评估疗效。使用血管性水肿生活质量问卷（AE-QoL）评估生活质量。结果：在APeX-S中，387例患者入组，从第1天开始接受贝曲司他150 mg （n=287）或110 mg （n=100）治疗。70例服用110 mg贝罗曲司他的患者在48周（46-71周）后转为使用150 mg贝罗曲司他。334例（86.3%）患者报告了240周的teae；最常见的是鼻咽炎（23.8%）、头痛（14.7%）、腹泻（14.5%）、上呼吸道感染（12.9%）和腹痛（11.1%）。贝罗曲司他治疗可改善HAE发作率和AE-QoL评分，直至96周，从第1天开始接受贝罗曲司他150mg治疗的患者改善更大。结论：本研究支持贝曲司他的长期安全性及其在预防HAE发作和改善生活质量方面的有效性。

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Long-term safety and efficacy of once-daily berotralstat in patients with hereditary angioedema

Background

Berotralstat is a once-daily oral medication for the prophylaxis of hereditary angioedema (HAE) attacks in patients aged 12 years and older.

Objective

To assess the long-term safety and efficacy of berotralstat in patients with HAE caused by C1 inhibitor deficiency.

Methods

APeX-S was a global, open-label phase 2 study (NCT03472040) assessing berotralstat 150 and 110 mg for up to 96 weeks in the United States and 240 weeks elsewhere. The primary objective was long-term safety and tolerability; secondary objectives included efficacy and impact on quality of life (QoL) of berotralstat. Safety was evaluated by means of treatment-emergent adverse events and laboratory analyses. Efficacy was assessed using the number and rate of HAE attacks, durability of response, and number and proportion of days with angioedema symptoms. QoL was evaluated using the Angioedema Quality of Life Questionnaire.

Results

In APeX-S, 387 patients were enrolled and received berotralstat 150 mg (n = 287) or 110 mg (n = 100) from day 1. A total of 70 patients on berotralstat 110 mg crossed over to berotralstat 150 mg after a median (range) of 48 (46–71) weeks. Treatment-emergent adverse events up to 240 weeks were reported by 334 patients (86.3%); the most common being nasopharyngitis (23.8%), headache (14.7%), diarrhea (14.5%), upper respiratory tract infection (12.9%), and abdominal pain (11.1%). Treatment with berotralstat led to improvements in HAE attack rates and Angioedema Quality of Life Questionnaire scores up to week 96, with greater improvements observed in patients who received berotralstat 150 mg from day 1.

Conclusion

This study supports the long-term safety of berotralstat and its efficacy in preventing HAE attacks and improving QoL.

Clinical Trial Registration

This trial was registered at ClinicalTrials.gov as NCT03472040 (https://clinicaltrials.gov/study/NCT03472040).

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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.