Clinical burden, treatment, and disease control in patients with chronic spontaneous urticaria: Real-world evidence.

Background: Chronic spontaneous urticaria (CSU) is an unpredictable inflammatory skin condition with substantial clinical burden that affects 0.23-0.78% of the United States population.

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.

Current and Emerging Therapeutics in Hereditary Angioedema.

Angioedema is characterized by transient movement of fluid from the vasculature into the interstitial space leading to subcutaneous or submucosal non-pitting edema. Current evidence suggests that most angioedema conditions can be grouped into 2 categories: mast cell-mediated (previously termed histaminergic) or bradykinin-mediated angioedema. Although effective therapies for mast cell-mediated angioedema have existed for decades, specific therapies for bradykinin-mediated angioedema have more recently been developed.

Efficacy and Safety of Donidalorsen for Hereditary Angioedema.

Background: Hereditary angioedema is a rare disorder characterized by episodic, potentially life-threatening swelling caused by kallikrein-kinin dysregulation. Long-term prophylaxis can stabilize this system. Donidalorsen, an antisense oligonucleotide, specifically reduces prekallikrein expression.

The future of therapeutic options for hereditary angioedema.

Hereditary angioedema (HAE) is a rare genetic condition causing unpredictable and severe episodes of angioedema that are debilitating and life-threatening. Moreover, HAE can be classified into HAE due to C1-esterase inhibitor deficiency (HAE-C1INH) or HAE with normal C1INH. Moreover, HAE-C1INH is subcategorized as types I and II based on deficient or dysfunctional circulating C1INH protein resulting from inherited or spontaneous mutations in the SERPING1 gene leading to uncontrolled factor XII/plasma kallikrein activation and excessive bradykinin production.

Clinical Progress in Hepatic Targeting for Novel Prophylactic Therapies in Hereditary Angioedema.

Hereditary angioedema (HAE) is typically caused by a deficiency of the protease inhibitor C1 inhibitor (C1INH). The absence of C1INH activity on plasma kallikrein and factor XIIa leads to overproduction of the vasoactive peptide bradykinin, with resulting angioedema. As the primary site of C1INH and prekallikrein production, the liver is recognized as an important therapeutic target in HAE, leading to the development of hepatic-focused treatment strategies such as GalNAc-conjugated antisense technology and gene modification.

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).

Hereditary angioedema outcomes in US patients switched from injectable long-term prophylactic medication to oral berotralstat.

Background: Berotralstat, a first-line, once-daily, oral plasma kallikrein inhibitor for long-term prophylaxis of hereditary angioedema (HAE), is an effective and well-tolerated treatment option.

Objective: To summarize the safety, effectiveness, and impact on treatment satisfaction in patients who switched from injectable long-term prophylactics to oral berotralstat monotherapy (150 mg daily) at US sites in the international open-label APeX-S study.

Methods: APeX-S was an open-label, Phase II study of berotralstat conducted in 22 countries.

Hereditary angioedema in older adults: Understanding the patient perspective.

Background: Hereditary angioedema (HAE) is a rare condition characterized by potentially fatal, recurrent episodes of painful swelling. Whereas there are limited studies evaluating the quality of life of individuals with HAE, none have evaluated the impact of HAE on older adults.

Objective: To evaluate the effect of HAE on older adults through qualitative methodology.

Evaluation of patient-reported outcome measures for on-demand treatment of hereditary angioedema attacks and design of KONFIDENT, a phase 3 trial of sebetralstat.

Background: Hereditary angioedema (HAE) with C1-inhibitor deficiency (HAE-C1-INH) is characterized by recurrent, debilitating episodes of swelling. Sebetralstat, an investigational oral plasma kallikrein inhibitor, demonstrated promising efficacy for on-demand treatment of HAE-C1-INH in a phase 2 trial. We describe the multipronged approach informing the design of KONFIDENT, a phase 3 randomized, placebo-controlled, three-way crossover trial evaluating the efficacy and safety of sebetralstat in patients aged ≥12 years with HAE-C1-INH.

Healthcare utilization of patients with hereditary angioedema treated with lanadelumab and subcutaneous C1-inhibitor concentrate.

New hereditary angioedema (HAE) treatments have become available in recent years for the treatment of HAE due to C1-inhibitor (C1-INH) deficiency, including two subcutaneous (SC) options: a monoclonal antibody (lanadelumab) and a plasma-derived C1-INH concentrate (SC-C1-INH). Limited real-world data on these therapies have been reported. The objective was to describe new users of lanadelumab and SC-C1-INH, including demographics, healthcare resource utilization (HCRU), costs, and treatment patterns before and after beginning treatment.

Long-term lanadelumab treatment improves health-related quality of life in patients with hereditary angioedema.

Background: Hereditary angioedema (HAE) is associated with a substantial disease burden. Lanadelumab reduced the HAE attack rate during 132 weeks of follow-up in the HELP open-label extension (OLE) Study (NCT02741596).

Objective: To measure the impact of long-term lanadelumab treatment on patient-reported outcomes (PROs).

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.

An investigational oral plasma kallikrein inhibitor for on-demand treatment of hereditary angioedema: a two-part, randomised, double-blind, placebo-controlled, crossover phase 2 trial.

Background: Guidelines recommend effective on-demand therapy for all individuals with hereditary angioedema. We aimed to assess the novel oral plasma kallikrein inhibitor, sebetralstat, which is in development, for on-demand treatment of hereditary angioedema attacks.

Methods: In this two-part phase 2 trial, individuals with type 1 or 2 hereditary angioedema aged 18 years or older were recruited from 25 sites, consisting of specialty outpatient centres, across nine countries in Europe and the USA.

Hereditary Angioedema With Normal C1 Inhibitor: US Survey of Prevalence and Provider Practice Patterns.

Background: Hereditary angioedema (HAE) with normal C1-INH (HAE-nl-C1INH) is phenotypically similar to HAE resulting from C1-INH deficiency (HAE-C1INH). Confirmatory diagnostic tests for HAE-nl-C1INH are limited and few clinical study data exist regarding management of the condition. Therefore, survey studies may provide initial estimates of prevalence, diagnosis, and management patterns of this condition.

Urticaria and Angioedema: Understanding Complex Pathomechanisms to Facilitate Patient Communication, Disease Management, and Future Treatment.

Chronic spontaneous urticaria (CSU) is primarily a T2-dominant disease with a complex genetic background. Skin mast cell activation can be induced not only via the IgE-FcεRI axis but also from several other distinct mechanisms, molecules, and receptors involved in CSU onset, persistence, and exacerbation. These include autoallergy, autoimmunity, central or peripheral neuroimmune dysregulation, activation of both extrinsic and intrinsic coagulation pathways, and microbial infections.

Hereditary Angioedema During Pregnancy: Considerations in Management.

In recent years, hereditary angioedema (HAE) management has substantially advanced but also become more complex with additional therapeutic options. Pregnancy significantly influences the clinical symptoms of HAE in many women because of estrogen effects or other physiologic factors, and also introduces important safety concerns related to HAE medications. Management of HAE during pregnancy requires clinicians to be familiar with the potential clinical course, triggers, and recommended treatment strategies to provide guidance and optimal medical management to women and families affected by the condition.

Consider Hereditary Angioedema in the Differential Diagnosis for Unexplained Recurring Abdominal Pain.

Health care providers are likely to encounter patients with recurrent unexplained abdominal pain. Because hereditary angioedema (HAE) is a rare disease, it may not be part of the differential diagnosis, especially for patients who do not have concurrent skin swelling in addition to abdominal symptoms. Abdominal pain is very common in patients with HAE, occurring in up to 93% of patients, with recurrent abdominal pain reported in up to 80% of patients.

Shared decision-making in the management of hereditary angioedema: An analysis of patient and physician perspectives.

Hereditary angioedema (HAE) is a rare genetic disorder characterized by recurrent, localized episodes of edema. Current treatment guidelines highlight the importance of shared decision-making (SDM) during implementation of HAE management plans. To determine what constitutes a successful SDM approach in HAE management.

Inhibition of Prekallikrein for Hereditary Angioedema.

Background: Hereditary angioedema is characterized by recurrent and unpredictable swellings that are disabling and potentially fatal. Selective inhibition of plasma prekallikrein production by antisense oligonucleotide treatment (donidalorsen) may reduce the frequency of attacks and the burden of disease.

Methods: In this phase 2 trial, we randomly assigned, in a 2:1 ratio, patients with hereditary angioedema with C1 inhibitor deficiency to receive four subcutaneous doses of either donidalorsen (80 mg) or placebo, with one dose administered every 4 weeks.

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.