Magerl Markus, Riedl Marc A, Arruda Luisa Karla, Bauer Andrea, Berardi Alejandro, Bernstein Jonathan A, Bouillet Laurence, Buckland Matthew, Buttgereit Thomas, Cohn Danny M, Craig Timothy, Criado Roberta F, Du-Thanh Aurélie, Fain Olivier, Gonçalo Margarida, Greve Jens, Grumach Anete Sevciovic, Guilarte Mar, Katelaris Constance, Kinaciyan Tamar, Latysheva Elena A, Lleonart Ramon, Llosa Oscar Calderón, Mansour Eli, Grivcheva-Panovska Vesna, Parisi Claudio, Rosario Filho Nelson Augusto, Santos Amélia Spínola, Staubach Petra, Valerieva Anna, Rodrigues Valle Solange Oliveira, Danese Sherry, Ulloa Julie, Audhya Paul K, Maurer Marcus
Angioedema Center of Reference and Excellence (ACARE), Institute of Allergology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Allergology and Immunology, Berlin, Germany.
J Allergy Clin Immunol Glob. 2025 Feb 27;4(3):100446. doi: 10.1016/j.jacig.2025.100446. eCollection 2025 Aug.
Hereditary angioedema (HAE) is a rare genetic disease, most frequently associated with deficiency or dysfunction in the C1 inhibitor protein. HAE with normal C1 inhibitor (HAE-nC1INH) lacks standardized diagnostic tests, limiting precise prevalence estimates and development of specific treatment guidelines.
This study sought to describe the global frequency, diagnostic pathway, and current treatment patterns of HAE-nC1INH.
Board-certified HAE-treating physicians from accredited Angioedema Centers of Reference and Excellence (ACAREs) were invited to complete a 27-item online survey between December 2022 and April 2023.
Thirty physicians from 30 ACAREs across 15 countries reported a mean of 71 (range, 11-148) patients with HAE assessed/treated within the previous 12 months. On average, physicians estimated 24% (range, 2-44%) of patients with HAE were diagnosed with HAE-nC1INH, most of whom were adults (88%). To diagnose HAE-nC1INH, physicians most commonly assessed family history and plasma C4 levels (90% each), and C1 function and quantitative levels (87% each). On-demand and prophylactic treatment patterns varied widely across countries, with an average (range) of 56% (33-100%) of patients receiving on-demand treatment only, and 37% (0-67%) receiving both on-demand and prophylactic treatment. Physicians identified the greatest unmet needs in HAE-nC1INH management as treatment specifically indicated for this patient population and availability of an oral treatment.
HAE-nC1INH may be more prevalent than previously reported. Importantly, our findings revealed varying diagnostic and treatment approaches. Validated, accessible diagnostic biomarkers and clinical outcomes derived from rigorous clinical trials assessing mechanistically based treatments would advance understanding and management of HAE-nC1INH.
遗传性血管性水肿（HAE）是一种罕见的遗传性疾病，最常与C1抑制蛋白的缺乏或功能障碍相关。C1抑制蛋白正常的HAE（HAE-nC1INH）缺乏标准化的诊断测试，这限制了精确的患病率估计和特定治疗指南的制定。
本研究旨在描述HAE-nC1INH的全球发病率、诊断途径和当前治疗模式。
2022年12月至2023年4月期间，邀请来自认可的血管性水肿参考与卓越中心（ACAREs）的获得委员会认证的HAE治疗医生完成一项包含27个项目的在线调查。
来自15个国家的30个ACAREs的30名医生报告称，在过去12个月内平均评估/治疗了71名（范围为11 - 148名）HAE患者。医生平均估计，24%（范围为2% - 44%）的HAE患者被诊断为HAE-nC1INH，其中大多数为成年人（88%）。为诊断HAE-nC1INH，医生最常评估家族史和血浆C4水平（各占90%），以及C1功能和定量水平（各占87%）。按需治疗和预防性治疗模式在各国差异很大，平均（范围）有56%（33% - 100%）的患者仅接受按需治疗，37%（0% - 67%）的患者接受按需治疗和预防性治疗。医生认为HAE-nC1INH管理中未满足的最大需求是针对该患者群体的特异性治疗以及口服治疗的可及性。
HAE-nC1INH可能比之前报道的更为普遍。重要的是，我们的研究结果揭示了不同的诊断和治疗方法。经过验证的、可及的诊断生物标志物以及来自评估基于机制治疗的严格临床试验的临床结果，将推动对HAE-nC1INH的理解和管理。
