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

Current treatments for long-term prophylaxis in hereditary angioedema have limitations.To assess the efficacy of lanadelumab, a fully human monoclonal antibody that selectively inhibits active plasma kallikrein, in preventing hereditary angioedema attacks.Phase 3, randomized, double-blind, parallel-group, placebo-controlled trial conducted at 41 sites in Canada, Europe, Jordan, and the United States. Patients were randomized between March 3, 2016, and September 9, 2016; last day of follow-up was April 13, 2017. Randomization was 2:1 lanadelumab to placebo; patients assigned to lanadelumab were further randomized 1:1:1 to 1 of the 3 dose regimens. Patients 12 years or older with hereditary a…

International consensus and practical guidelines on the gynecologic and obstetric management of female patients with hereditary angioedema caused by C1 inhibitor deficiency

Background There are a limited number of publications on the management of gynecologic/obstetric events in female patients with hereditary angioedema caused by C1 inhibitor deficiency (HAE-C1-INH). Objective We sought to elaborate guidelines for optimizing the management of gynecologic/obstetric events in female patients with HAE-C1-INH. Methods A roundtable discussion took place at the 6th C1 Inhibitor Deficiency Workshop (May 2009, Budapest, Hungary). A review of related literature in English was performed. Results Contraception : Estrogens should be avoided. Barrier methods, intrauterine devices, and progestins can be used. Pregnancy : Attenuated androgens are contraindicated and should …

Long-Term Outcomes with Subcutaneous C1-Inhibitor Replacement Therapy for Prevention of Hereditary Angioedema Attacks: An Open-Label Extension Study of the COMPACT Trial

Validation of the Angioedema Control Test (AECT)—A Patient-Reported Outcome Instrument for Assessing Angioedema Control

Background Recurrent angioedema (RA) is an important clinical problem in routine care and emergency medicine. As of recently, the only validated tools to specifically assess disease status in patients with RA were diary-type activity assessments and angioedema-related quality-of-life questionnaires. Although these tools are particularly helpful in clinical studies, they were not designed to determine disease control or to guide treatment decisions. To close this gap, the Angioedema Control Test (AECT) was published recently. Objective To test the AECT for its validity and reliability, and to identify a cutoff value to aid treatment decisions. Methods Two AECT versions with a recall period o…

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

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 up…

Long-term outcomes with subcutaneous C1-inhibitor replacement therapy for prevention of hereditary angioedema attacks

Background For the prevention of attacks of hereditary angioedema (HAE), the efficacy and safety of subcutaneous human C1-esterase inhibitor (C1-INH[SC]; HAEGARDA, CSL Behring) was established in the 16-week Clinical Study for Optimal Management of Preventing Angioedema with Low-Volume Subcutaneous C1-Inhibitor Replacement Therapy (COMPACT). Objective To assess the long-term safety, occurrence of angioedema attacks, and use of rescue medication with C1-INH(SC). Methods Open-label, randomized, parallel-arm extension of COMPACT across 11 countries. Patients with frequent angioedema attacks, either study treatment-naive or who had completed COMPACT, were randomly assigned (1:1) to 40 IU/kg or …

Development of the Angioedema Control Test—A patient‐reported outcome measure that assesses disease control in patients with recurrent angioedema

Background Recurrent angioedema (AE) is an important clinical problem in the context of chronic urticaria (mast cell mediator-induced), ACE-inhibitor intake and hereditary angioedema (both bradykinin-mediated). To help patients obtain control of their recurrent AE is a major treatment goal. However, a tool to assess control of recurrent AE is not yet available. This prompted us to develop such a tool, the Angioedema Control Test (AECT). Methods After a conceptional framework was developed for the AECT, a list of potential AECT items was generated by a combined approach of patient interviews, literature review and expert input. Subsequent item reduction was based on impact analysis, inter-it…

Hereditary angioedema in children and adolescents - A consensus update on therapeutic strategies for German-speaking countries.

Background/methods At a consensus meeting in August 2018, pediatricians and dermatologists from German-speaking countries discussed the therapeutic strategy for the treatment of pediatric patients with type I and II hereditary angioedema due to C1 inhibitor deficiency (HAE-C1-INH) for Germany, Austria, and Switzerland, taking into account the current marketing approval status. HAE-C1-INH is a rare disease that usually presents during childhood or adolescence with intermittent episodes of potentially life-threatening angioedema. Diagnosis as early as possible and an optimal management of the disease are important to avoid ineffective therapies and to properly treat swelling attacks. This art…

Definition, aims, and implementation of GA [sup] 2 LEN/HAEi Angioedema Centers of Reference and Excellence

This document summarizes the aims of GA2 LEN/HAEi Angioedema Centers of Reference and Excellence (ACAREs) and elaborates the requirements that ACAREs must fulfill to become certified. It also provides (see Appendix S1) background information on GA2LEN and HAEi, including HAEi member organizations and regional patient advocates, on why we need an Angioedema Center of Reference and Excellence (ACARE) program and network, and on the accreditation and certification process, governance and funding, and on the interaction with other GA2LEN networks of centers of reference and excellence. The protocols, aims, requirements, and provisions related to becoming a certified CARE are based on (a) the ex…

C1 Inhibitor for Routine Prophylaxis in Patients with Hereditary Angioedema: Interim Results from a European Registry Study

Hereditary angiodema: a current state-of-the-art review, VII: Canadian Hungarian 2007 International Consensus Algorithm for the Diagnosis, Therapy, and Management of Hereditary Angioedema.

Background We published the Canadian 2003 International Consensus Algorithm for the Diagnosis, Therapy, and Management of Hereditary Angioedema (HAE; C1 inhibitor [C1-INH] deficiency) in 2004. Objective To ensure that this consensus remains current. Methods In collaboration with the Canadian Network of Rare Blood Disorder Organizations, we held the second Canadian Consensus discussion with our international colleagues in Toronto, Ontario, on February 3, 2006, and reviewed its content at the Fifth C1 Inhibitor Deficiency Workshop in Budapest on June 2, 2007. Papers were presented by international investigators, and this consensus algorithm approach resulted. Results This consensus algorithm …