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The Chronic Angioedema Registry (CARE) is an international disease registry that aims to improve patient care for recurrent angioedema. It collects data through questionnaires completed by physicians and patients to assess disease control, quality of life, and treatment responses. However, the outcomes may not apply to less severe cases typically seen in primary care or community settings, and the findings may not be generalizable to patients from diverse ethnic backgrounds. The document also lists conflicts of interest for authors involved in the CARE study, who have disclosed financial relationships with pharmaceutical companies and other organizations. The study received approval from the Ethics Committee of Charité—Universitätsmedizin Berlin. [Extracted from the article]

Background: The aim was to evaluate long‐term effectiveness and safety of lanadelumab in patients ≥12 y old with hereditary angioedema (HAE) 1/2 (NCT02741596). Methods: Rollover patients completing the HELP Study and continuing into HELP OLE received one lanadelumab 300 mg dose until first attack (dose‐and‐wait period), then 300 mg q2wks (regular dosing stage). Nonrollovers (newly enrolled) received lanadelumab 300 mg q2wks from day 0. Baseline attack rate for rollovers: ≥1 attack/4 weeks (based on run‐in period attack rate during HELP Study); for nonrollovers: historical attack rate ≥1 attack/12 weeks. The planned treatment period was 33 months. Results: 212 patients participated (109 rollovers, 103 nonrollovers); 81.6% completed ≥30 months on study (mean [SD], 29.6 [8.2] months). Lanadelumab markedly reduced mean HAE attack rate (reduction vs baseline: 87.4% overall). Patients were attack free for a mean of 97.7% of days during treatment; 81.8% and 68.9% of patients were attack free for ≥6 and ≥12 months, respectively. Angioedema Quality‐of‐Life total and domain scores improved from day 0 to end of study. Treatment‐emergent adverse events (TEAEs) (excluding HAE attacks) were reported by 97.2% of patients; most commonly injection site pain (47.2%) and viral upper respiratory tract infection (42.0%). Treatment‐related TEAEs were reported by 54.7% of patients. Most injection site reactions resolved within 1 hour (70.2%) or 1 day (92.6%). Six (2.8%) patients discontinued due to TEAEs. No treatment‐related serious TEAEs or deaths were reported. Eleven treatment‐related TEAEs of special interest were reported by seven (3.3%) patients. Conclusion: Lanadelumab demonstrated sustained efficacy and acceptable tolerability with long‐term use in HAE patients. [ABSTRACT FROM AUTHOR]

Background: The Icatibant Outcome Survey (IOS; NCT01034969) is a Shire‐sponsored, international, observational study monitoring the safety and effectiveness of icatibant, a bradykinin B2 receptor antagonist approved for the acute treatment of adults with hereditary angioedema with C1 inhibitor deficiency (HAE‐C1‐INH). Objective: To report IOS data comparing demographic and icatibant treatment outcomes in patients with HAE‐C1‐INH from Germany to HAE‐C1‐INH patients from 11 other IOS countries. Methods: A descriptive, retrospective, comparative analysis of data from 685 IOS patients with HAE‐C1‐INH from seven centres in Germany (n = 93) vs. centres from Austria, Brazil, Czech Republic, Denmark, France, Greece, Israel, Italy, Spain, Sweden and the United Kingdom (n = 592, July 2009–January 2017). Icatibant treatment outcomes were retrieved from patients with complete attack outcome data for time to treatment, time to resolution and attack duration (160 attacks in 42 German patients and 1442 attacks in 251 patients from other IOS countries). Results: German patients reported significantly fewer severe/very severe attacks (38.7% vs. 57.5%, respectively; P < 0.001). The proportion of attacks treated with a single icatibant injection was significantly higher in German patients (97.1% vs. 91.6%, P = 0.0003). The median time to treatment (0.0 h vs. 1.5 h), time to resolution (3.0 h vs. 7.0 h) and attack duration (4.3 h vs. 10.5 h) in German patients vs. other IOS countries were all significantly shorter (all P < 0.0001). No meaningful differences were identified between patients from Germany and other countries with regard to sex, median age at enrolment, median age at symptom onset and median age at diagnosis. Conclusion: German IOS patients share similar demographic characteristics to patients from other IOS countries yet treat their attacks with icatibant significantly earlier and have markedly fewer severe or very severe attacks. Factors including regional access to and availability of icatibant may drive these outcomes and warrant further investigation. [ABSTRACT FROM AUTHOR]

Abstract: Background: Effective inhibition of plasma kallikrein may have significant benefits for patients with hereditary angioedema due to deficiency of C1 inhibitor (C1‐INH‐HAE) by reducing the frequency of angioedema attacks. Avoralstat is a small molecule inhibitor of plasma kallikrein. This study (OPuS‐2) evaluated the efficacy and safety of prophylactic avoralstat 300 or 500 mg compared with placebo. Methods: OPuS‐2 was a Phase 3, multicenter, randomized, double‐blind, placebo‐controlled, parallel‐group study. Subjects were administered avoralstat 300 mg, avoralstat 500 mg, or placebo orally 3 times per day for 12 weeks. The primary efficacy endpoint was the angioedema attack rate based on adjudicator‐confirmed attacks. Results: A total of 110 subjects were randomized and dosed. The least squares (LS) mean attack rates per week were 0.589, 0.675, and 0.593 for subjects receiving avoralstat 500 mg, avoralstat 300 mg, and placebo, respectively. Overall, 1 subject in each of the avoralstat groups and no subjects in the placebo group were attack‐free during the 84‐day treatment period. The LS mean duration of all confirmed attacks was 25.4, 29.4, and 31.4 hours for the avoralstat 500 mg, avoralstat 300 mg, and placebo groups, respectively. Using the Angioedema Quality of Life Questionnaire (AE‐QoL), improved QoL was observed for the avoralstat 500 mg group compared with placebo. Avoralstat was generally safe and well tolerated. Conclusions: Although this study did not demonstrate efficacy of avoralstat in preventing angioedema attacks in C1‐INH‐HAE, it provided evidence of shortened angioedema episodes and improved QoL in the avoralstat 500 mg treatment group compared with placebo. [ABSTRACT FROM AUTHOR]

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? [ABSTRACT FROM AUTHOR]

Background Hereditary angioedema ( HAE), caused by deficiency in C1-inhibitor (C1- INH), leads to unpredictable edema of subcutaneous tissues with potentially fatal complications. As surgery can be a trigger for edema episodes, current guidelines recommend preoperative prophylaxis with C1- INH or attenuated androgens in patients with HAE undergoing surgery. However, the risk of an HAE attack in patients without prophylaxis has not been quantified. Objectives This analysis examined rates of perioperative edema in patients with HAE not receiving prophylaxis. Methods This was a retrospective analysis of records of randomly selected patients with HAE type I or II treated at the Frankfurt Comprehensive Care Centre. These were examined for information about surgical procedures and the presence of perioperative angioedema. Results A total of 331 patients were included; 247 underwent 700 invasive procedures. Of these procedures, 335 were conducted in 144 patients who had not received prophylaxis at the time of surgery. Categories representing significant numbers of procedures were abdominal ( n = 113), ENT ( n = 71), and gynecological ( n = 58) procedures. The rate of documented angioedema without prophylaxis across all procedures was 5.7%; in 24.8% of procedures, the presence of perioperative angioedema could not be excluded, leading to a maximum potential risk of 30.5%. Predictors of perioperative angioedema could not be identified. Conclusion The risk of perioperative angioedema in patients with HAE type I or II without prophylaxis undergoing surgical procedures ranged from 5.7% to 30.5% ( CI 3.5-35.7%). The unpredictability of HAE episodes supports current international treatment recommendations to consider short-term prophylaxis for all HAE patients undergoing surgery. [ABSTRACT FROM AUTHOR]

Self-administration of therapy can help hereditary angioedema (HAE) patients regain control of their disease or reduce its impact and improve the quality of their lives. However, data from a self-administration survey, and subsequent discussion at an international HAE expert meeting, identified several barriers to self-administration therapy. These barriers include difficulty in administration technique, availability of nursing resources and the mental capacity of the patient. Encouragingly, international HAE experts identified that once a patient has acquired self-administration skills, they generally retain them in the long-term. As patient uptake increases, it was recommended that follow-up management plans should be established to address any issues from the patient's perspective. Copyright © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Hereditary angioedema (HAE) is an autosomal dominant disease that manifests as intermittent acute swellings of the skin and mucosal surfaces, which, in the gastrointestinal tract and larynx, may even be fatal. HAE results from functional deficiency of the C1 inhibitor (C1INH) protein, which plays a key role in the classical pathway of complement activation. C1INH is the sole inhibitor of the activated proteases C1r and C1s, and is the major regulator of activated coagulation Factor XII and plasma kallikrein, which limits the generation of the vasoactive peptide bradykinin. In this paper, we report on the genetic analysis of 173 families (including 326 members) with a clinical diagnosis of HAE. Direct sequencing, Southern blotting and quantitative PCR by the MLPA method were used to screen for mutations in C1INH (SERPING1). In 142 families (82.1%), a causative C1INH gene mutation could be identified. A total of 80 novel point mutations of C1INH not published previously were detected in 96 pedigrees (including 172 members). Our results corroborate C1INH (SERPING1) deficiency as a disease of extreme allelic heterogeneity with almost each individual family carrying their own mutation. Routine molecular genetic analysis is an effective way of confirming the clinical diagnosis and identifying mutation carriers early on before any clinical manifestation becomes apparent. It is, therefore, a valuable tool in prevention and adequate treatment of acute and life-threatening oedema. Copyright © 2008 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]