Treatment effect of switching from intravenous to subcutaneous C1-inhibitor for prevention of hereditary angioedema attacks: COMPACT subgroup findings

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The international WAO/EAACI guideline for the management of hereditary angioedema – the 2017 revision and update

Abstract Hereditary Angioedema (HAE) is a rare and disabling disease. Early diagnosis and appropriate therapy are essential. This update and revision of the global guideline for HAE provides up-to-date consensus recommendations for the management of HAE. In the development of this update and revision of the guideline, an international expert panel reviewed the existing evidence and developed 20 recommendations that were discussed, finalized and consented during the guideline consensus conference in June 2016 in Vienna. The final version of this update and revision of the guideline incorporates the contributions of a board of expert reviewers and the endorsing societies. The goal of this guideline update and revision is to provide clinicians and their patients with guidance that will assist them in making rational decisions in the management of HAE with deficient C1-inhibitor (type 1) and HAE with dysfunctional C1-inhibitor (type 2). The key clinical questions covered by these recommendations are: 1) How should HAE-1/2 be defined and classified?, 2) How should HAE-1/2 be diagnosed?, 3) Should HAE-1/2 patients receive prophylactic and/or on-demand treatment and what treatment options should be used?, 4) Should HAE-1/2 management be different for special HAE-1/2 patient groups such as pregnant/lactating women or children?, and 5) Should HAE-1/2 management incorporate self-administration of therapies and patient support measures? This article is co-published with permission in Allergy and the World Allergy Organization Journal

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 goal of these recommendations and guideline is to help physicians and their patients in making rational decisions in the management of HAE with deficient C1 inhibitor (type 1) and HAE with dysfunctional C1 inhibitor (type 2), by providing guidance on common and important clinical issues, such as: (1) How should HAE be diagnosed? (2) When should HAE patients receive prophylactic on top of on-demand treatment and what treatments should be used? (3) What are the goals of treatment? (4) Should HAE management be different for special HAE patient groups such as children or pregnant/breast-feeding women? and (5) How should HAE patients monitor their disease activity, impact, and control? It is also the intention of this guideline to help establish global standards for the management of HAE and to encourage and facilitate the use of recommended diagnostics and therapies for all patients

Lanadelumab demonstrates rapid and sustained prevention of hereditary angioedema attacks.

BackgroundLanadelumab demonstrated efficacy in preventing hereditary angioedema (HAE) attacks in the phase 3 HELP Study.ObjectiveTo assess time to onset of effect and long-term efficacy of lanadelumab, based on exploratory findings from the HELP Study.MethodsEligible patients with HAE type I/II received lanadelumab 150 mg every 4 weeks (q4wks), 300 mg q4wks, 300 mg q2wks, or placebo. Ad hoc analyses evaluated day 0-69 findings using a Poisson regression model accounting for overdispersion. Least-squares mean monthly HAE attack rate for lanadelumab was compared with placebo. Intrapatient comparisons for days 0-69 versus steady state (days 70-182) used a paired t test for continuous endpoints or Kappa statistics for categorical endpoints.ResultsOne hundred twenty-five patients were randomized and treated. During days 0-69, mean monthly attack rate was significantly lower with lanadelumab (0.41-0.76) vs placebo (2.04), including attacks requiring acute treatment (0.33-0.61 vs 1.66) and moderate/severe attacks (0.31-0.48 vs 1.33, all P ≤ .001). More patients receiving lanadelumab vs placebo were attack free (37.9%-48.1% vs 7.3%) and responders (85.7%-100% vs 26.8%). During steady state, the efficacy of lanadelumab vs placebo was similar or improved vs days 0-69. Intrapatient differences were significant with lanadelumab 300 mg q4wks for select outcomes. Lanadelumab efficacy was durable-HAE attack rate was consistently lower vs placebo, from the first 2 weeks of treatment through study end. Treatment emergent adverse events were comparable during days 0-69 and 70-182.ConclusionProtection with lanadelumab started from the first dose and continued throughout the entire study period

Lanadelumab demonstrates rapid and sustained prevention of hereditary angioedema attacks.

BackgroundLanadelumab demonstrated efficacy in preventing hereditary angioedema (HAE) attacks in the phase 3 HELP Study.ObjectiveTo assess time to onset of effect and long-term efficacy of lanadelumab, based on exploratory findings from the HELP Study.MethodsEligible patients with HAE type I/II received lanadelumab 150 mg every 4 weeks (q4wks), 300 mg q4wks, 300 mg q2wks, or placebo. Ad hoc analyses evaluated day 0-69 findings using a Poisson regression model accounting for overdispersion. Least-squares mean monthly HAE attack rate for lanadelumab was compared with placebo. Intrapatient comparisons for days 0-69 versus steady state (days 70-182) used a paired t test for continuous endpoints or Kappa statistics for categorical endpoints.ResultsOne hundred twenty-five patients were randomized and treated. During days 0-69, mean monthly attack rate was significantly lower with lanadelumab (0.41-0.76) vs placebo (2.04), including attacks requiring acute treatment (0.33-0.61 vs 1.66) and moderate/severe attacks (0.31-0.48 vs 1.33, all P ≤ .001). More patients receiving lanadelumab vs placebo were attack free (37.9%-48.1% vs 7.3%) and responders (85.7%-100% vs 26.8%). During steady state, the efficacy of lanadelumab vs placebo was similar or improved vs days 0-69. Intrapatient differences were significant with lanadelumab 300 mg q4wks for select outcomes. Lanadelumab efficacy was durable-HAE attack rate was consistently lower vs placebo, from the first 2 weeks of treatment through study end. Treatment emergent adverse events were comparable during days 0-69 and 70-182.ConclusionProtection with lanadelumab started from the first dose and continued throughout the entire study period