CRISPR-Based Therapy for Hereditary Angioedema.

Background: Hereditary angioedema is a rare genetic disease characterized by severe and unpredictable swelling attacks. NTLA-2002 is an in vivo gene-editing therapy that is based on clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein 9. NTLA-2002 targets the gene encoding kallikrein B1 ().

The complexities of decision-making associated with on-demand treatment of hereditary angioedema (HAE) attacks.

Background: Hereditary angioedema (HAE) is characterized by debilitating attacks of tissue swelling in various locations. While guidelines recommend the importance of early on-demand treatment, recent data indicate that many patients delay or do not treat their attacks.

Objective: This survey aimed to investigate patient behavior and evaluate the key factors that drive on-demand treatment decision-making, as reported by those living with HAE.

The autoimmune rheumatological presentation of Common Variable Immunodeficiency Disorders with an overview of genetic testing.

Primary immunodeficiency Disorders (PIDS) are rare, mostly monogenetic conditions which can present to a number of specialties. Although infections predominate in most PIDs, some individuals can manifest autoimmune or inflammatory sequelae as their initial clinical presentation. Identifying patients with PIDs can be challenging, as some can present later in life.

CRISPR-Cas9 In Vivo Gene Editing of for Hereditary Angioedema.

Background: Hereditary angioedema is a rare genetic disease that leads to severe and unpredictable swelling attacks. NTLA-2002 is an in vivo gene-editing therapy based on clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein 9. NTLA-2002 targets the gene encoding kallikrein B1 (), with the goal of lifelong control of angioedema attacks after a single dose.

A Review of Randomized Controlled Trials of Hereditary Angioedema Long-Term Prophylaxis with C1 Inhibitor Replacement Therapy: Alleviation of Disease Symptoms Is Achievable.

Through its fluctuating disease activity and unpredictable attacks, hereditary angioedema (HAE) imposes a substantial patient burden. To minimize HAE burden and improve quality of life, treatment should involve individualized management strategies that address on-demand therapy and short-term/long-term prophylaxis. Goals of long-term prophylaxis include reducing the number, severity, and burden of HAE attacks.

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.

The Icatibant Outcome Survey: 10 years of experience with icatibant for patients with hereditary angioedema.

In patients with hereditary angioedema (HAE), bradykinin causes swelling episodes by activating bradykinin B receptors. Icatibant, a selective bradykinin B receptor antagonist, is approved for on-demand treatment of HAE attacks. The Icatibant Outcome Survey (IOS; NCT01034969) is an ongoing observational registry initiated in 2009 to monitor the effectiveness/safety of icatibant in routine clinical practice.

The Role of Herpes Viruses in Pulmonary Fibrosis.

Pulmonary fibrosis (PF) is a serious lung disease which can result from known genetic or environmental exposures but is more commonly idiopathic (IPF). In familial PF (FPF), the majority of identified causal genes play key roles in the maintenance of telomeres, the protective end structures of chromosomes. Recent evidence suggests that short telomeres may also be implicated causally in a significant proportion of idiopathic cases.

Assessment and management of disease burden and quality of life in patients with hereditary angioedema: a consensus report.

Background: Hereditary angioedema (HAE) is a rare disease characterized by unpredictable, potentially life-threatening attacks, resulting in significant physical and emotional burdens for patients and families. To optimize care for patients with HAE, an individualized management plan should be considered in partnership with the physician, requiring comprehensive assessment of the patient's frequency and severity of attacks, disease burden, and therapeutic control. Although several guidelines and consensus papers have been published concerning the diagnosis and treatment of HAE, there has been limited specific clinical guidance on the assessment of disease burden and quality of life (QoL) in this patient population.

Managing Chronic Urticaria and Recurrent Angioedema Differently with Advancing Age.

Angioedema and urticaria affect people of all ages. Accurate diagnosis and optimum management is essential for healthy aging. Older people continue to experience mast cell-mediated urticaria and angioedema, with a higher prevalence of autoimmune and a lower prevalence of autoallergic disease.

Impact of lanadelumab on health-related quality of life in patients with hereditary angioedema in the HELP study.

Background: An objective of the phase 3 HELP Study was to investigate the effect of lanadelumab on health-related quality of life (HRQoL) in patients with hereditary angioedema (HAE).

Methods: Patients with HAE-1/2 received either lanadelumab 150 mg every 4 weeks (q4wks; n = 28), 300 mg q4wks (n = 29), 300 mg every 2 weeks (q2wks; n = 27), or placebo (n = 41) for 26 weeks (days 0-182). The Angioedema Quality of Life Questionnaire (AE-QoL) was administered monthly, consisting of four domain (functioning, fatigue/mood, fears/shame, nutrition) and total scores.

Lanadelumab demonstrates rapid and sustained prevention of hereditary angioedema attacks.

Background: Lanadelumab demonstrated efficacy in preventing hereditary angioedema (HAE) attacks in the phase 3 HELP Study.

Objective: To assess time to onset of effect and long-term efficacy of lanadelumab, based on exploratory findings from the HELP Study.

Methods: Eligible patients with HAE type I/II received lanadelumab 150 mg every 4 weeks (q4wks), 300 mg q4wks, 300 mg q2wks, or placebo.

Subcutaneous C1 inhibitor for prevention of attacks of hereditary angioedema: additional outcomes and subgroup analysis of a placebo-controlled randomized study.

Background: Hereditary angioedema (HAE) is a debilitating disorder resulting from C1-esterase inhibitor (C1-INH) deficiency. In the COMPACT phase 3 study the prophylactic use of a subcutaneous C1 inhibitor (C1-INH [SC], HAEGARDA, CSL Behring) twice weekly significantly reduced the frequency of acute edema attacks. Analysis of treatment effects by subgroups, onset of effect, and other exploratory analysis have not been reported.

Elderly versus younger patients with hereditary angioedema type I/II: patient characteristics and safety analysis from the Icatibant Outcome Survey.

Background: Hereditary angioedema with C1 inhibitor deficiency (C1-INH-HAE) is characterized by recurrent swelling in subcutaneous or submucosal tissues. Symptoms often begin by age 5-11 years and worsen during puberty, but attacks can occur at any age and recur throughout life. Disease course in elderly patients is rarely reported.

Hereditary angioedema: an update on causes, manifestations and treatment.

Hereditary angioedema is a rare genetic disorder caused by deficiency of C1 esterase inhibitor (C1-INH) and characterized by recurrent episodes of severe swelling that affect the limbs, face, intestinal tract and airway. Since laryngeal oedema can be life-threatening as a result of asphyxiation, correct diagnosis and management of hereditary angioedema is vital. Hereditary angioedema attacks are mediated by bradykinin, the production of which is regulated by C1-INH.

Effect of Lanadelumab Compared With Placebo on Prevention of Hereditary Angioedema Attacks: A Randomized Clinical Trial.

Importance: Current treatments for long-term prophylaxis in hereditary angioedema have limitations.

Objective: To assess the efficacy of lanadelumab, a fully human monoclonal antibody that selectively inhibits active plasma kallikrein, in preventing hereditary angioedema attacks.

Design, Setting, And Participants: Phase 3, randomized, double-blind, parallel-group, placebo-controlled trial conducted at 41 sites in Canada, Europe, Jordan, and the United States.

Improvement in diagnostic delays over time in patients with hereditary angioedema: findings from the Icatibant Outcome Survey.

The objective of this analysis was to evaluate the change over time in age at first symptoms, age at diagnosis, and delay in diagnosis using data from the Icatibant Outcome Survey (IOS). Patients with a diagnosis of C1-INH-HAE who were born before the year 1990 and who were diagnosed before they reached 25 years of age were included in the analysis. Both age at diagnosis and delay in diagnosis of C1-INH-HAE appear to decline with later decade of birth, despite wide variation across the countries assessed, suggesting that improved disease awareness causes increased rates of earlier diagnosis over time.