按需治疗遗传性血管性水肿的口服sebetralstat和静脉注射rhc1-inh的间接治疗比较

IF 5.8 2区医学 Q1 ALLERGY

Annals of Allergy Asthma & Immunology Pub Date : 2024-10-25 DOI:10.1016/j.anai.2024.08.114

A. Wang , H. Li , M. Magerl , T. Craig , M. Manning , N. Hummel , P. Audhya , J. Bernstein

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引用次数: 0

摘要

导言：遗传性血管性水肿（HAE）按需试验的设计和终点存在很大的异质性，这使得间接治疗比较（ITC）具有挑战性。Sebetralstat是一种按需口服血浆allikrein抑制剂，在一项3期随机安慰剂对照试验中证明了其疗效和安全性。根据系统性文献回顾，在已发表的 HAE 按需治疗 3 期试验中，只有一项试验，即静脉注射重组人 C1 酯酶抑制剂（IV-rhC1-INH）的关键性试验，报告了主要终点可比的相关数据，以实现与赛百特的 ITC。方法根据现有数据，进行了贝叶斯固定效应网络荟萃分析（NMA），间接比较了sebetralstat（NCT05259917）和IV-rhC1-INH（NCT01188564、NCT00225147、NCT00262301）的疗效和安全性结果。采用随机效应模型进行了敏感性分析。结果NMA固定效应模型发现，在症状开始缓解的时间上，sebetralstat 300 mg和IV-rhC1-INH 50 IU/kg之间没有显著差异（HR [95% CI] 0.96 [0.42-2.15] to 1.19 [0.58-2.45]）。对基线发作严重程度进行调整后，MAIC 显示，无论基线人口统计学变量是否匹配，塞贝曲司他与静脉注射-rhC1-INH 的治疗结果在数字上都更有利。NMA发现，治疗相关不良事件没有明显差异。结论这项ITC研究发现，sebetralstat和IV-rhC1-INH在症状开始缓解的时间和总体治疗相关不良事件方面没有显著差异。

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INDIRECT TREATMENT COMPARISON OF ORAL SEBETRALSTAT AND INTRAVENOUS RHC1-INH AS ON-DEMAND TREATMENTS FOR HEREDITARY ANGIOEDEMA

Introduction

Substantial heterogeneity in hereditary angioedema (HAE) on-demand trial designs and endpoints make indirect treatment comparison (ITC) challenging. Sebetralstat, an investigational oral on-demand plasma kallikrein inhibitor, demonstrated efficacy and safety in a phase 3 randomized placebo-controlled trial, in which the primary endpoint of time to beginning of symptom relief was measured by the Patient Global Impression of Change scale. Based on a systematic literature review, among published phase 3 HAE on-demand trials, only one, the pivotal trial for intravenous recombinant human C1 esterase inhibitor (IV-rhC1-INH), reported relevant data for a comparable primary endpoint to enable an ITC with sebetralstat.

Methods

Based on available data, a Bayesian fixed-effects network meta-analysis (NMA) was conducted to indirectly compare the efficacy and safety outcomes of sebetralstat (NCT05259917) and IV-rhC1-INH (NCT01188564, NCT00225147, NCT00262301). Sensitivity analyses were examined with random effects models. Matching-adjusted indirect comparison (MAIC) of efficacy outcome was also performed, adjusting for differences in baseline clinical and demographic characteristics.

Results

The NMA fixed effects model found no significant differences in time to beginning of symptom relief between sebetralstat 300 mg and IV-rhC1-INH 50 IU/kg (HR [95% CI] 0.96 [0.42-2.15] to 1.19 [0.58-2.45]). After adjusting for baseline attack severity, MAIC showed numerically favorable results with sebetralstat vs IV-rhC1-INH, regardless of whether baseline demographics variables were matched. NMA found no significant differences in treatment-related adverse events. All sensitivity analyses returned consistent results.

Conclusions

This ITC study found no significant differences in time to beginning of symptom relief and overall treatment-related adverse events between sebetralstat and IV-rhC1-INH.

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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.