Idiopathic non-mast cell angioedema: Treatment insights from global experts.

Idiopathic non-mast cell angioedema (INMA) is a rare disease typified by recurrent attacks of cutaneous and subcutaneous swelling. Every attack carries the potential for severe morbidity and, in the case of laryngeal involvement, mortality. Whereas therapies approved for hereditary angioedema (HAE) have been used in the care of patients with INMA, little is known with regard to their efficacy for the treatment of this disease.

Development and validation of a US quality of life instrument for hereditary angioedema due to C1 inhibitor deficiency.

Background: Hereditary angioedema (HAE) attacks are unpredictable, cause a substantial and enduring burden of illness, and are potentially fatal. Because of issues unique to the US health care system, there is a need for a US-validated, HAE-specific quality of life (QoL) instrument.

Objective: To develop and validate a US HAE-specific QoL instrument according to US Food and Drug Administration guidelines and established methodologies.

Contact System Activation and Bradykinin Generation in Angioedema: Laboratory Assessment and Biomarker Utilization.

The role of contact system activation has been clearly established in the pathogenesis of hereditary angioedema due to C1 inhibitor deficiency (HAE-C1INH). C1 inhibitor (C1INH)-protease complexes, levels of functional C1INH, plasma kallikrein activation, and cleavage of high-molecular-weight kininogen have each been associated with disease activity. More recently, HAE with normal levels of C1INH (HAE-nl-C1INH) has been recognized.

Classification, Diagnosis, and Pathology of Angioedema Without Hives.

A clear disease classification schema coupled with an understanding of the specific mechanisms involved in the different types of angioedema without hives informs the diagnostic assessment. The recommended approach involves several key steps. Foremost is the recognizing of the clinical clues which allow for the differentiation of mast cell-mediated disorders from bradykinin-mediated angioedema.

A phase 2 open-label extension study of prekallikrein inhibition with donidalorsen for hereditary angioedema.

Background: Hereditary angioedema (HAE) is a potentially fatal disease characterized by unpredictable, recurrent, often disabling swelling attacks. In a randomized phase 2 study, donidalorsen reduced HAE attack frequency and improved patient quality-of-life (ISIS721744-CS2, NCT04030598). We report the 2-year interim analysis of the phase 2 open-label extension (OLE) study (ISIS 721744-CS3, NCT04307381).

The US Hereditary Angioedema Association Scientific Registry: hereditary angioedema demographics, disease severity, and comorbidities.

Background: Hereditary angioedema (HAE) and idiopathic nonhistaminergic angioedema (INHA) are ultra-rare diseases whose natural histories and comorbidities are incompletely understood.

Objective: To develop a national patient-centric registry to address these deficiencies in our knowledge and improve our ability to assess the real-world impact of therapeutic interventions.

Methods: Data from members of the US HAE Association were collected into an online registry between 2009 and April 7, 2021.

Lower serum 15-HETE level predicts nasal ILC2 accumulation during COX-1 inhibition in AERD.

Background: Aspirin-exacerbated respiratory disease (AERD) is associated with high levels of cysteinyl leukotrienes, prostaglandin D, and low levels of prostaglandin E. Further, 15-hydroxyeicosatetraenoic acid (15-HETE) levels may have predictive value in therapeutic outcomes of aspirin desensitization. Accumulation of nasal group 2 innate lymphoid cells (ILC2s) has been demonstrated during COX-1 inhibition in AERD, although the relationships between tissue ILC2 accumulation, reaction symptom severity, and novel lipid biomarkers are unknown.

Hereditary Angioedema: Impact of COVID-19 pandemic stress upon disease related morbidity and well-being.

Individuals with hereditary angioedema (HAE) experience stress-related sequelae, including enhanced disease morbidity and reduced quality of life. The pervasive societal strain that surround the coronavirus disease 2019 (COVID-19) pandemic may theoretically pose a disproportionate risk for patients with HAE. To dissect the interrelationship(s) among the COVID-19 pandemic, stress, and HAE disease-related morbidity and overall well-being.

Therapeutic monoclonal antibodies with a focus on hereditary angioedema.

Monoclonal antibodies (mAbs) have been shown to be effective and generally safe across a continually expanding list of therapeutic areas. We describe the advantages and limitations of mAbs as a therapeutic option compared with small molecules. Specifically, we discuss a novel mAb in the treatment of hereditary angioedema (HAE), a rare and potentially life-threatening condition characterized by recurrent unpredictable swelling attacks.

The international WAO/EAACI guideline for the management of hereditary angioedema - The 2021 revision and update.

Hereditary Angioedema (HAE) is a rare and disabling disease for which early diagnosis and effective therapy are critical. This revision and update of the global WAO/EAACI guideline on the diagnosis and management of HAE provides up-to-date guidance for the management of HAE. For this update and revision of the guideline, an international panel of experts reviewed the existing evidence, developed 28 recommendations, and established consensus by an online DELPHI process.

The international WAO/EAACI guideline for the management of hereditary angioedema-The 2021 revision and update.

Hereditary angioedema (HAE) is a rare and disabling disease for which early diagnosis and effective therapy are critical. This revision and update of the global WAO/EAACI guideline on the diagnosis and management of HAE provides up-to-date guidance for the management of HAE. For this update and revision of the guideline, an international panel of experts reviewed the existing evidence, developed 28 recommendations, and established consensus by an online DELPHI process.

COVID-19 and hereditary angioedema: Incidence, outcomes, and mechanistic implications.

Patients with hereditary angioedema (HAE) have been postulated to be at increased risk for coronavirus disease 2019 (COVID-19) infection due to inherent dysregulation of the plasma kallikrein-kinin system. Only limited data have been available to explore this hypothesis. To assess the interrelationship(s) between COVID-19 and HAE.

Consensus on treatment goals in hereditary angioedema: A global Delphi initiative.

Background: Hereditary angioedema (HAE) is a rare, life-threatening genetic disorder characterized by recurrent episodes of subcutaneous or submucosal angioedema. The ultimate goals of treatment for HAE remain ill-defined.

Objectives: The aim of this Delphi process was to define the goals of HAE treatment and to examine which factors should be considered when assessing disease control and normalization of the patient's life.

The Expanding Spectrum of Mutations in Hereditary Angioedema.

The evolution in the knowledge of rare genetic diseases such as hereditary angioedema (HAE) has increased at a parallel pace with the development of new molecular tools. The deficiency of C1 inhibitor (C1-INH) has been recognized as the main cause of HAE (HAE-C1-INH) since the 1960s, but the discovery of the wide spectrum of mutations affecting the C1-INH gene (SERPING1) was possible only from the late 1980s, when Sanger sequencing became available and more accessible worldwide. Nevertheless, the involvement of other genes in HAE was discovered only in 2006 with the description of mutations in the F12 gene in patients with HAE and normal C1-INH.

Long-term health-related quality of life in patients treated with subcutaneous C1-inhibitor replacement therapy for the prevention of hereditary angioedema attacks: findings from the COMPACT open-label extension study.

Background: Long-term prophylaxis with subcutaneous C1-inhibitor (C1-INH[SC]; HAEGARDA, CSL Behring) in patients with hereditary angioedema (HAE) due to C1-INH deficiency (C1-INH-HAE) was evaluated in an open-label extension follow-up study to the international, double-blind, placebo-controlled COMPACT study. The current analysis evaluated patient-reported health-related quality of life (HRQoL) data from 126 patients in the open-label extension study randomized to treatment with C1-INH(SC) 40 IU/kg (n = 63) or 60 IU/kg (n = 63) twice weekly for 52 weeks. HRQoL was evaluated at the beginning of the open-label study and at various time points using the European Quality of Life-5 Dimensions Questionnaire (EQ-5D), the Hospital Anxiety and Depression Scale (HADS), the Work Productivity and Activity Impairment Questionnaire (WPAI), and the Treatment Satisfaction Questionnaire for Medication.

Assessing the cost and quality-of-life impact of on-demand-only medications for adults with hereditary angioedema.

Novel subcutaneous (SC) prophylactic therapies are transforming the treatment landscape of hereditary angioedema (HAE). Although questions are being raised about their cost, little attention has been paid to the cost and quality of life (QoL) impact of using on-demand-only medications. We assessed the overall economic burden of on-demand-only treatment for HAE and compared patient QoL with patients who received novel SC prophylactic therapies.

Intranasal ketorolac, diagnosis, and desensitization for aspirin-exacerbated respiratory disease.

Background: Intranasal ketorolac has been proposed as a diagnostic test for aspirin-exacerbated respiratory disease (AERD) and a faster, safer, and reliable addition to facilitating aspirin (ASA) desensitization.

Objective: We conducted the first prospective study to dissect the impact of intranasal ketorolac incorporation during ASA desensitization vs standard oral protocols in concert with evaluating its diagnostic use for AERD.

Methods: Patients with AERD were enrolled in a prospective open-label observational study between November 2006 and August 2013.

Hereditary angioedema: On-demand treatment of angioedema attacks.

The availability of effective acute treatment for angioedema has been fundamental in reducing the burden of illness for patients with hereditary angioedema (HAE). In building on the foundation of scientific advances that elucidate the pathomechanism(s) of attacks related to vascular permeability, novel targeted on-demand treatments have been developed and approved. These therapies have provided the means to arrest episodes of swelling, which, in the past, had the potential to inexorably lead to morbidity, and even mortality, for patients with HAE.