Comparative Efficacy of Recombinant C1 Inhibitor Versus Sebetralstat for On-Demand Treatment of Hereditary Angioedema Attacks: A Matching-Adjusted Indirect Treatment Comparison.

IF 4 3区医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL

Advances in Therapy Pub Date : 2026-05-02 DOI:10.1007/s12325-026-03605-4

John Anderson, Nihal Narsipur, Douglas Jones, Andrew Smith, Anurag Relan, Emily Aiello, Neil Roskell, Adam Gough, Sakshi Jindal, Ketsia Habimana, Hannah Kilvert, H Henry Li, Amanda Harrington

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引用次数: 0

Abstract

Introduction: Prompt and effective on-demand treatment is critical in hereditary angioedema (HAE). Although multiple on-demand therapies are available, including recombinant human C1 esterase inhibitor (rhC1-INH) and sebetralstat, no head-to-head efficacy trials exist.

Methods: A series of indirect treatment comparisons evaluated the relative efficacy of US Food and Drug Administration-approved doses of intravenous rhC1-INH (50 U/kg for patients weighing < 84 kg; 4200 U otherwise) vs oral sebetralstat (600 mg) for the on-demand treatment of HAE attacks. Patient-level data from rhC1-INH trials (C1 1310, C1 1205, and C1 1304 [placebo only]) were reweighted to match aggregate baseline characteristics (i.e., prophylaxis use, pooled attack location) from the sebetralstat KONFIDENT trial; matching variables were identified from a validated, clinician-informed study of treatment effect modifiers. In the primary analysis, time to complete resolution (TTCR) and redosing were compared using unanchored matching-adjusted indirect comparisons. TTCR subgroup analyses were performed for variables not matched for in the primary analysis due to population differences (i.e., attack severity, time to treatment). Scenario and sensitivity analyses were performed to support TTCR results; a scenario analysis was performed to support redosing results. Hazard ratios (HRs) and odds ratios (ORs), with 95% confidence intervals (CIs), were estimated using a weighted Cox proportional hazards model and a weighted logistic regression model, respectively.

Results: In the primary analysis, rhC1-INH was associated with a statistically significant 4.5-fold increased likelihood of achieving complete resolution (HR 4.52; 95% CI 2.84-7.18) and a significant 82% reduction in redosing (OR 0.18; 95% CI 0.06-0.53) vs sebetralstat. Similar results for TTCR were observed in subgroup analyses of patients with severe/very severe baseline attacks and patients receiving earlier treatment (within the median time to treatment). Scenario and sensitivity analyses confirmed the robustness of these findings.

Conclusions: rhC1-INH provides significantly faster symptom resolution and lower redosing rates vs sebetralstat.

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重组C1抑制剂与Sebetralstat按需治疗遗传性血管性水肿发作的比较疗效：一项匹配调整的间接治疗比较。

及时有效的按需治疗对于遗传性血管性水肿（HAE）至关重要。虽然有多种按需治疗，包括重组人C1酯酶抑制剂（rhC1-INH）和sebetralstat，但没有头对头的疗效试验。方法：一系列间接治疗比较评估了美国食品和药物管理局批准的静脉注射rhC1-INH剂量的相对疗效（50 U/kg）。结果：在初步分析中，rhC1-INH与sebetralstat相比，实现完全缓解的可能性增加了4.5倍（HR 4.52; 95% CI 2.84-7.18），再给药减少了82% (OR 0.18; 95% CI 0.06-0.53)，具有统计学意义。在基线发作严重/非常严重的患者和接受早期治疗的患者（在治疗的中位时间内）的亚组分析中，观察到TTCR的类似结果。情景分析和敏感性分析证实了这些发现的稳健性。结论：与sebetralstat相比，rhC1-INH可显著更快地缓解症状并降低再给药率。

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

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.