Hereditary angioedema (HAE) is a genetic disease resulting in deficiency (type I) or dysfunction (type II) in the complement-1 esterase inhibitor (C1-INH) protein and subsequent uncontrolled activation of the kallikrein kinin system [1]. The symptoms of a HAE attack are well recognized and include swelling in the extremities or face, abdominal pain caused by intestinal swelling, and respiratory difficulties as a result of laryngeal and airway angioedema [2]. The frequency and severity of HAE attacks are highly variable between patients and even can vary within a patient, over their lifetime, making each patient’s HAE attack journey highly individualized [3].

A recent prevalence analysis reported 8,904 HAE patients in the United States (US), which aligns with previous prevalence estimates of 1 in 50,000 within the global population (range 1 in 10,000 to 1 in 150,000) [4,5,6,7]. The rarity of HAE may contribute to diagnostic delays for many patients, with time to conclusive diagnosis ranging from 2 to 13.5 years [4, 8].

The recent international World Allergy Organization (WAO)/European Academy of Allergy and Clinical Immunology (EAACI) guideline for HAE acknowledges that early diagnosis and effective therapy are critical for the management of this disabling disease [9]. The goal of HAE treatment is to achieve complete disease control and normalize patients’ lives [9]. Current management of HAE includes the use of medications targeting the kallikrein-kinin pathway for on-demand treatment of acute angioedema events (HAE attacks) with the objective of relieving acute symptoms as quickly and completely as possible [10]. As attacks are unpredictable and potentially life-threatening, it is essential that all HAE patients have effective on-demand therapy readily available [9]. Long-term prophylaxis is recommended for some HAE patients to reduce the frequency of attacks. The need for long-term prophylaxis is highly individualized based on attack frequency and severity, and patient preference [11].

Guidelines state that HAE attacks should be treated early with intravenous (IV) plasma-derived C1-INH and recombinant human C1-INH, plasma kallikrein inhibitor ecallantide administered subcutaneously by a health professional, or self-injected subcutaneous (SC) bradykinin B2 receptor antagonist icatibant, and that early treatment provides far better clinical outcomes than late treatment [11].

For long-term prophylactic treatment, guidelines recommend the use of IV or SC plasma-derived C1-INH, the SC plasma kallikrein monoclonal antibody lanadelumab, or orally administered plasma kallikrein inhibitor berotralstat. Guidelines also recommend an individualized approach to prophylaxis, including careful and regular monitoring of HAE patients who use long-term prophylactic treatment in order to inform dose optimization, with the goal of improving tolerability, adherence to therapy, and quality of life [2, 11].

It is recognized that current HAE treatments are effective and have greatly improved the lives of patients with HAE. Despite these benefits, treatment administration may impose additional burden to some patients and caregivers, as most prophylactic and all on-demand therapies are administered by SC or IV injection [12,13,14]. Patients have indicated that the route of administration is the factor they consider the most important in their choice of HAE treatment, citing the need for less ”traumatic” administration with oral therapies preferred over SC and IV [13].

Availability of self-administered on-demand parenteral treatments has improved health-related quality of life and HAE attack management. However, deciding when to initiate on-demand therapy may be challenging for patients as attack symptoms may escalate over hours and attacks can be unpredictable and vary in intensity. Patient education is crucial for appropriate and early initiation of on-demand therapy and to minimize attack severity and duration.

However, decision-making associated with on-demand treatment administration as reported by patients and the impact of this process on the patient’s HAE attack journey have not been fully described in the literature. Characterizing patient behavior and understanding the patient perspective are essential for addressing the factors restricting the optimal use of on-demand treatment for HAE attacks. Patients’ experiences, including the self-reported reasons for delaying treatment or not treating attacks, would offer valuable insights into the decision-making process surrounding on-demand treatment administration.

Here, we describe the findings of a patient survey that aimed to encompass the overall behaviors and decision-making process regarding the on-demand treatment of HAE attacks. We present an evaluation of the factors that drive the on-demand treatment decision-making process, including reasons to delay or not treat an attack, as reported by those living with HAE.