Efficacy and safety of garadacimab, a factor XIIa inhibitor for hereditary angioedema prevention (VANGUARD): a global, multicentre, randomised, double-blind, placebo-controlled, phase 3 trial.

BACKGROUND: Hereditary angioedema is a rare and potentially life-threatening genetic disease that is associated with kallikrein-kinin system dysregulation. Garadacimab (CSL312), a novel, fully-human monoclonal antibody that inhibits activated factor XII (FXIIa), is being studied for the prevention of hereditary angioedema attacks. The aim of this study was to evaluate the efficacy and safety of once-monthly subcutaneous administrations of garadacimab as prophylaxis for hereditary angioedema. METHODS: VANGUARD was a pivotal, multicentre, randomised, double-blind, placebo-controlled, phase 3 trial that recruited patients (aged ≥12 years) with type I or type II hereditary angioedema across seven countries (Canada, Germany, Hungary, Israel, Japan, the Netherlands, and the USA). Eligible patients were randomly assigned (3:2) to receive garadacimab or placebo for 6 months (182 days) by an interactive response technology (IRT) system. Randomisation was stratified by age (≤17 years vs >17 years) and baseline attack rate (1 to <3 attacks per month vs ≥3 attacks per month) for the adult group. The randomisation list and code were kept by the IRT provider during the study, with no access by site staff and funding representatives. All patients and investigational site staff, and representatives from the funder (or their delegates) with direct interaction with the study sites or patients, were masked to treatment assignment in a double-blind fashion. Randomly assigned patients received a 400-mg loading dose of subcutaneous garadacimab as two 200-mg injections or volume-matched placebo on day 1 of the treatment period, followed by five additional self-administered (or caregiver-administered) monthly doses of 200-mg subcutaneous garadacimab or volume-matched placebo. The primary endpoint was the investigator-assessed time-normalised number of hereditary angioedema attacks (number of hereditary angioedema attacks per month) during the 6-month treatment period (day 1 to day 182). Safety was evaluated in patients who received at least one dose of garadacimab or placebo. The study is registered with the EU Clinical Trials Register, 2020-000570-25 and ClinicalTrials.gov, NCT04656418. FINDINGS: Between Jan 27, 2021, and June 7, 2022, we screened 80 patients, 76 of whom were eligible to enter the run-in period of the study. Of 65 eligible patients with type I or type II hereditary angioedema, 39 were randomly assigned to garadacimab and 26 to placebo. One patient was randomly assigned in error and did not enter the treatment period (no dose of study drug received), resulting in 39 patients assigned to garadacimab and 25 patients assigned to placebo being included. 38 (59%) of 64 participants were female and 26 (41%) were male. 55 (86%) of 64 participants were White, six (9%) were Asian (Japanese), one (2%) was Black or African American, one (2%) was Native Hawaiian or Other Pacific Islander, and one (2%) was listed as other. During the 6-month treatment period (day 1 to day 182), the mean number of investigator-confirmed hereditary angioedema attacks per month was significantly lower in the garadacimab group (0·27, 95% CI 0·05 to 0·49) than in the placebo group (2·01, 1·44 to 2·57; p<0·0001), corresponding to a percentage difference in means of -87% (95% CI -96 to -58; p<0·0001). The median number of hereditary angioedema attacks per month was 0 (IQR 0·00-0·31) for garadacimab and 1·35 (1·00-3·20) for placebo. The most common treatment-emergent adverse events were upper-respiratory tract infections, nasopharyngitis, and headaches. FXIIa inhibition was not associated with an increased risk of bleeding or thromboembolic events. INTERPRETATION: Monthly garadacimab administration significantly reduced hereditary angioedema attacks in patients aged 12 years and older compared with placebo and had a favourable safety profile. Our results support the use of garadacimab as a potential prophylactic therapy for the treatment of hereditary angioedema in adolescents and adults. FUNDING: CSL Behring.

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). METHODS: In the OLE, the on-treatment study period consisted of fixed (weeks 1-13, donidalorsen 80 mg subcutaneously every 4 weeks [Q4W]) and flexible (weeks 17-105, donidalorsen 80 mg Q4W, 80 mg every 8 weeks [Q8W], or 100 mg Q4W) dosing periods. The primary outcome was incidence and severity of treatment-emergent adverse events (TEAEs). The secondary outcomes included efficacy, pharmacodynamic, and quality-of-life assessments. RESULTS: Seventeen patients continued in the OLE study. No serious TEAEs or TEAEs leading to treatment discontinuation were reported. Mean monthly HAE attack rate was 96% lower than the study run-in baseline rate (mean, 0.06/month; 95% confidence interval [CI], 0.02-0.10; median, 0.04 on-treatment vs. mean, 2.70/month; 95% CI, 1.94-3.46; median, 2.29 at baseline). Mean monthly attack rate for Q8W dosing (n = 8) was 0.29 (range, 0.0-1.7; 95% CI, -0.21 to 0.79; median, 0.00). Mean plasma prekallikrein and D-dimer concentrations decreased, and Angioedema Quality of Life Questionnaire total score improved from baseline to week 105 with donidalorsen. CONCLUSION: The 2-year interim results of this phase 2 OLE study of donidalorsen in patients with HAE demonstrated no new safety signals; donidalorsen was well tolerated. There was durable efficacy with a 96% reduction in HAE attacks.

Long term outcome of C1-esterase inhibitor deficiency.

Hereditary angioedema (HAE) is a rare hereditary disorder characterized by episodic swelling and life-threatening airway obstruction caused by laryngeal angioedema. In most HAE patients, reduced level of serum C1-Inhibitor (type-I-HAE) or presence of aberrant C1-Inhibitor (type-II-HAE) result in the lost of regulation of the complementary system and contact activation system with downstream over-activation of bradykinin - the chief mediator leading to angioedema. Type-III HAE (HAE-nl-C1INH) is rare without deficient or dysfunction of C1-Inhibitor, often with genetic aberrant related to the contact activation system. The prevalence of HAE in the population is estimated at 1 in 50,000 individuals, often with early onset, but due to the heterogeneity of the disease, there is frequently a significant delay in diagnosis. Recently, better awareness by physicians, more access to diagnostic tools, better management and prophylaxis has decreased morbidity and mortality. A focus in HAE patient care shift from management of attacks with on-demand medication, to use of prophylaxis to reduce attacks has improved the overall quality of life of patients with HAE. One area in HAE research that has not been emphasized is the long-term consequence of C1-INH deficiency in HAE patients, other than the typical manifestations of HAE, as evidence have emerged linking this disorder with increased risk of cardiovascular diseases, auto-immune disorders, and malignancy. This review aims to gather the current knowledge and evidence of potential consequence of C1-Inhibitor deficiency in HAE aside from angioedema with emphasis in the improvement of long-term care and overall quality of life for HAE patients.

Small molecule drugs for atopic dermatitis, rheumatoid arthritis, and hereditary angioedema.

OBJECTIVE: To review recent trends in the development of targeted small molecule drugs (SMDs) for the treatment of immunologically driven disorders, including atopic dermatitis, rheumatoid arthritis, and hereditary angioedema. DATA SOURCES: Data sources included peer-reviewed published literature from the PubMed database, published abstracts from scientific and medical meetings, and medication information from the Drugs@FDA database. STUDY SELECTIONS: Articles with primary or retrospective trial results, articles with patient or physician survey results, articles providing expert perspectives, and commentary on chronic immunologic disorders, Food and Drug Administration package inserts, and abstracts from scientific meetings were selected. RESULTS: Targeted biological therapies have greatly improved response rates and symptom relief for patients with long-term immunologically driven disorders over the past 2 decades. However, recent advances in the understanding of molecular pathways involved in the pathogenesis of these disorders have led to the development of novel targeted SMDs, such as tofacitinib and berotralstat, that can be delivered orally or topically. Few head-to-head studies that compare the safety and efficacy of biologics to SMDs in immunologically driven disorders exist, although some studies suggest that oral and topical modes of administration are preferred by patients and may improve patient quality of life over time. CONCLUSION: Scientific advances have led to an increase in the development of targeted SMDs for the treatment of chronic immunologic disorders, which may revolutionize the management of these diseases. Head-to-head studies and real-world evidence are needed to fully compare treatment attributes between biologics and SMDs, including safety, efficacy, adherence, impact on quality of life, and cost-effectiveness.

Global perceptions of the current and future impacts of COVID-19 on hereditary angioedema management.

Background: The coronavirus disease 2019 (COVID-19) pandemic has greatly affected health-care provision across the globe. Management of chronic ailments has become challenging because of the strained health-care resources and social distancing measures that prevent on-site clinical visits and treatments. Hereditary angioedema (HAE) is a debilitating, chronic disease characterized by unpredictable swelling attacks in various parts of the body. Controlling HAE symptoms often requires long-term prophylactic medication use and regular medical care; however, limited scientific information has been published about HAE medical care during the COVID-19 pandemic. Objective: To gather patient and health-care professional (HCP) perspectives on the global impact that COVID-19 has had, and the future impact it will have on HAE medical care and to identify differences in perceptions across economic and geographic boundaries. Methods: We conducted two independent but similar online global surveys to capture patient and HCP perspectives on the impact that COVID-19 has had, and the future impact it will have on HAE medical care. Results: Both patients and HCPs globally reported that the pandemic has limited the availability of HAE medical care, and they expect the restrictions to continue far beyond the pandemic. In addition, the results of our study suggested that telehealth use has increased across the globe but has been more successfully implemented in high-income countries. Conclusion: Patients and HCPs expect that HAE-related care will be negatively impacted by the pandemic for many years. Disparities in medical care and technologic infrastructure may exacerbate these challenges in non-high-income countries. Supportive tools and global infrastructure should be established to provide aid to non-high-income countries throughout the pandemic and several years after.

Oral once-daily berotralstat for the prevention of hereditary angioedema attacks: A randomized, double-blind, placebo-controlled phase 3 trial.

BACKGROUND: Berotralstat (BCX7353) is an oral, once-daily inhibitor of plasma kallikrein in development for the prophylaxis of hereditary angioedema (HAE) attacks. OBJECTIVE: Our aim was to determine the efficacy, safety, and tolerability of berotralstat in patients with HAE over a 24-week treatment period (the phase 3 APeX-2 trial). METHODS: APeX-2 was a double-blind, parallel-group study that randomized patients at 40 sites in 11 countries 1:1:1 to receive once-daily berotralstat in a dose of 110 mg or 150 mg or placebo (Clinicaltrials.gov identifier NCT03485911). Patients aged 12 years or older with HAE due to C1 inhibitor deficiency and at least 2 investigator-confirmed HAE attacks in the first 56 days of a prospective run-in period were eligible. The primary efficacy end point was the rate of investigator-confirmed HAE attacks during the 24-week treatment period. RESULTS: A total of 121 patients were randomized; 120 of them received at least 1 dose of the study drug (n = 41, 40, and 39 in the 110-mg dose of berotralstat, 150-mg of dose berotralstat, and placebo groups, respectively). Berotralstat demonstrated a significant reduction in attack rate at both 110 mg (1.65 attacks per month; P = .024) and 150 mg (1.31 attacks per month; P < .001) relative to placebo (2.35 attacks per month). The most frequent treatment-emergent adverse events that occurred more with berotralstat than with placebo were abdominal pain, vomiting, diarrhea, and back pain. No drug-related serious treatment-emergent adverse events occurred. CONCLUSION: Both the 110-mg and 150-mg doses of berotralstat reduced HAE attack rates compared with placebo and were safe and generally well tolerated. The most favorable benefit-to-risk profile was observed at a dose of 150 mg per day.

Androgen use in hereditary angioedema: A critical appraisal and approaches to transitioning from androgens to other therapies.

Background: Hereditary angioedema (HAE) is a rare genetic disorder clinically characterized by recurrent attacks of subcutaneous and mucosal swelling. Attenuated androgens have been a prophylactic treatment option to reduce the frequency of HAE attacks for > 4 decades. However, the advent of effective on-demand treatments and highly effective, more tolerable, long-term prophylactic therapies has led to a decline in the use of attenuated androgens for the management of HAE in regions where newer therapies are available. A consensus about the best approach for discontinuing or tapering off attenuated androgen therapy does not exist. Objective: To develop a consensus on androgen tapering for patients with HAE. Methods: We sent an open-ended survey about androgen tapering to 21 physicians who treat HAE, 12 of whom responded. We reviewed the collective experience of the participating physicians in combination with results from a literature review on the topic. Results: The survey and literature review underscored potential concerns related to rapid androgen withdrawal in patients with HAE, including physician and patient concerns that the frequency and severity of attacks would abruptly worsen. In addition, discontinuation of attenuated androgens may have the potential for transient adverse effects, such as an increase in the rate of attacks or effects related to hormone withdrawal. Our survey showed that physicians often taper androgens to prevent increases in HAE attacks and possible withdrawal complications. Conclusion: Based on both experiences of the physicians who responded to our survey and reports in the endocrine literature, we provided recommendations for androgen tapering. However, we noted that the likelihood of adverse effects due to androgen withdrawal in patients with HAE is poorly understood and requires further study.

Patient perspectives on the treatment burden of injectable medication for hereditary angioedema.

Hereditary angioedema (HAE) is a rare, chronic disease characterized by debilitating swelling episodes in various parts of the body. Patients experience significant burdens related to the symptoms and management of HAE, which can affect their daily lives and reduce their overall quality of life. Prophylactic treatment options have expanded in the past decade to the benefit of patients; however, these therapies require scheduled injections, which can be painful, burdensome, and time consuming. We conducted an online survey of patients with HAE in the USA to better understand their experiences with available prophylactic medications and the associated treatment burdens. Our survey results suggest that most patients are satisfied with their current therapies but desire novel medications with a simpler route of administration and that, although most patients experience significant treatment-related burdens, they learn to cope with these challenges over time.

Caregivers' role in managing hereditary angioedema and perceptions of treatment-related burden.

Hereditary angioedema (HAE) is a rare genetic disease that results in recurrent, debilitating, and potentially life-threatening swelling episodes in the extremities, genitals, gastrointestinal tract, and upper airway. Patients can experience significant burdens related to their disease. Informal or familial caregivers often support patients with HAE and likely share in the disease-related burdens, although there are limited HAE caregiver-focused reports in the scientific literature. In the United States, we conducted an online survey of adults caring for an individual with HAE to better understand their experiences with the disease and identify psychosocial impacts of providing care for a patient with HAE. Thirty caregivers provided responses to the survey. Most caregivers were family members of the care recipient and many had HAE themselves. Caregivers reported participating in a number of medical-related tasks and experiencing some burdens as a result of caring for a person with HAE.

Physician and patient perspectives on the management of hereditary angioedema: a survey on treatment burden and needs.

Hereditary angioedema (HAE) is a rare disorder caused by genetic mutations that lead to recurrent episodes of swelling in various parts of the body. Prophylactic treatment is common for patients with HAE, and the therapeutic options have expanded in recent years. The current standard of care for prophylactic HAE therapies is subcutaneous treatment, which can be self-administered at home, greatly improving patient quality of life. As new therapies emerge, it is important for patients and physicians to discuss the risks and benefits associated with each treatment to develop an individualized approach to HAE management. We conducted surveys of patients with HAE and physicians who treat patients with HAE to identify prescribing trends for prophylactic HAE treatments and the impact that such treatments has on patients. Our results confirmed that newer, subcutaneous therapies are prescribed for HAE prophylaxis more frequently than other therapies in the United States and that treatment burdens still exist for patients with HAE. We found that physicians and patients were not always aligned on how treatment choices affect patients' lives, which may mean that there are opportunities for enhanced patient-physician dialog and shared decision-making in HAE management in the United States.

Rhinitis 2020: A practice parameter update.

This comprehensive practice parameter for allergic rhinitis (AR) and nonallergic rhinitis (NAR) provides updated guidance on diagnosis, assessment, selection of monotherapy and combination pharmacologic options, and allergen immunotherapy for AR. Newer information about local AR is reviewed. Cough is emphasized as a common symptom in both AR and NAR. Food allergy testing is not recommended in the routine evaluation of rhinitis. Intranasal corticosteroids (INCS) remain the preferred monotherapy for persistent AR, but additional studies support the additive benefit of combination treatment with INCS and intranasal antihistamines in both AR and NAR. Either intranasal antihistamines or INCS may be offered as first-line monotherapy for NAR. Montelukast should only be used for AR if there has been an inadequate response or intolerance to alternative therapies. Depot parenteral corticosteroids are not recommended for treatment of AR due to potential risks. While intranasal decongestants generally should be limited to short-term use to prevent rebound congestion, in limited circumstances, patients receiving regimens that include an INCS may be offered, in addition, an intranasal decongestant for up to 4 weeks. Neither acupuncture nor herbal products have adequate studies to support their use for AR. Oral decongestants should be avoided during the first trimester of pregnancy. Recommendations for use of subcutaneous and sublingual tablet allergen immunotherapy in AR are provided. Algorithms based on a combination of evidence and expert opinion are provided to guide in the selection of pharmacologic options for intermittent and persistent AR and NAR.

POPS case: A 30-year-old Filipino woman with fevers, lymphadenopathy, painful scalp lesions, and a neck mass.

We described a case of a 30-year-old Filipino woman who presented with fevers, night sweats, left hip pain, painful scalp lesions, and a neck mass. Symptoms began 6 months earlier, with nasal drainage, fever, cough, and occasional hemoptysis, which did not resolve with outpatient antibiotics. A further workup revealed lymphadenopathy and several lytic bone lesions. Her hospital course was later further complicated by the development of a tracheoesophageal fistula secondary to an esophageal mass and, then later, aseptic meningitis. Extensive diagnostic workup and immunologic tests were performed and finally led to the diagnosis. Here, we discussed the diagnostic workup and pathophysiology of the underlying condition. This case illustrated the importance of appropriate immunologic workup to make the diagnosis of a rare condition that proves to be clinically significant and presents challenges in management.

Advances in managing COPD related to α1 -antitrypsin deficiency: An under-recognized genetic disorder.

α1 -Antitrypsin deficiency (AATD) predisposes individuals to chronic obstructive pulmonary disease (COPD) and liver disease. Despite being commonly described as rare, AATD is under-recognized, with less than 10% of cases identified. The following is a comprehensive review of AATD, primarily for physicians who treat COPD or asthma, covering the genetics, epidemiology, clinical presentation, screening and diagnosis, and treatments of AATD. For patients presenting with liver and/or lung disease, screening and diagnostic tests are the only methods to determine whether the disease is related to AATD. Screening guidelines have been established by organizations such as the World Health Organization, European Respiratory Society, and American Thoracic Society. High-risk groups, including individuals with COPD, nonresponsive asthma, bronchiectasis of unknown etiology, or unexplained liver disease, should be tested for AATD. Current treatment options include augmentation therapy with purified AAT for patients with deficient AAT levels and significant lung disease. Recent trial data suggest that lung tissue is preserved by augmentation therapy, and different dosing schedules are currently being investigated. Effective management of AATD and related diseases also includes aggressive avoidance of smoking and biomass burning, vaccinations, antibiotics, exercise, good diet, COPD medications, and serial assessment.

Understanding alpha-1 antitrypsin deficiency: A review with an allergist's outlook.

Alpha-1 antitrypsin (AAT) is the prototypical protease inhibitor from the serine protease inhibitor (serpin) superfamily that protects lung tissue from proteolytic damage by inhibiting neutrophil elastase. Approximately 1 in 2750 to 1 in 4500 individuals have an autosomal codominant condition that leads to a deficiency of circulating AAT. In individuals with AAT deficiency (AATD), AAT is retained in liver cells, which predisposes them to liver disease, and does not reach lung tissues through circulation, where it normally acts as the primary natural regulator of proteolytic activity in the pulmonary tissues, which thus leads to lung disease. Despite being commonly labeled as a rare disease, AATD is one of the most common autosomal genetic disorders and is considered highly underrecognized, with ≤10% of individuals suspected with AATD identified. Screening guidelines have been established, and the diagnosis is easy to confirm when the condition is suspected. Early recognition is key to prevent morbidity and mortality associated with the disease. For this reason, all patients with chronic obstructive pulmonary disease and patients with asthma and fixed obstruction should be tested to exclude the diagnosis of AATD. Augmentation therapy of the deficient protein is available for those with significant lung disease and protein deficiency, and analysis of recent data supported preservation of lung tissue with this treatment. In this review, oriented toward specialists in allergy and immunology, we focused our discussion on the presentation, diagnosis, and treatment of pulmonary symptoms of AATD.

Circulating microRNAs as biomarkers in patients with allergic rhinitis and asthma.

BACKGROUND: MicroRNAs (miRNAs) are emerging as important regulatory molecules that might be involved in the pathogenesis of various diseases. Circulating miRNAs might be noninvasive biomarkers to diagnose and characterize asthma and allergic rhinitis (AR). OBJECTIVE: We sought to determine whether miRNAs are differentially expressed in the blood of asthmatic patients compared with those in the blood of nonasthmatic patients with AR and nonallergic nonasthmatic subjects. Furthermore, we sought to establish whether miRNAs could be used to characterize or subtype asthmatic patients. METHODS: Expression of plasma miRNAs was measured by using real-time quantitative PCR in 35 asthmatic patients, 25 nonasthmatic patients with AR, and 19 nonallergic nonasthmatic subjects. Differentially expressed miRNAs were identified by using Kruskal-Wallis 1-way ANOVA with Bonferroni P value adjustment to correct for multiple comparisons. A random forest classification algorithm combined with a leave-one-out cross-validation approach was implemented to assess the predictive capacities of the profiled miRNAs. RESULTS: We identified 30 miRNAs that were differentially expressed among healthy, allergic, and asthmatic subjects. These miRNAs fit into 5 different expression pattern groups. Among asthmatic patients, miRNA expression profiles identified 2 subtypes that differed by high or low peripheral eosinophil levels. Circulating miR-125b, miR-16, miR-299-5p, miR-126, miR-206, and miR-133b levels were most predictive of allergic and asthmatic status. CONCLUSIONS: Subsets of circulating miRNAs are uniquely expressed in patients with AR and asthmatic patients and have potential for use as noninvasive biomarkers to diagnose and characterize these diseases.

Risk factors associated with 30-day asthma readmissions.

OBJECTIVES: Assess factors that increase the odds of 30-day asthma readmissions to hospitals. METHODS: Retrospective chart review between 1/1/2002 to 12/31/2012 of pediatric and adult patients with the primary diagnosis of asthma readmitted within 30 days after the index admission was performed. Patients were identified from billing database for asthma ICD 9 code (493.9). Inclusion criteria were: physician confirmed asthma diagnosis, one or more asthma admissions and accessible medical records. RESULTS: A total of 95 patients with multiple asthma readmissions were included in the final analysis. Thirty-seven patients (39%) were readmitted for asthma within 30 days and 58 patients (61%) had readmission in a 30-365-day period. Demographic characteristics were not significantly different between groups. Bivariate analysis showed that factors associated with higher likelihood of readmissions were a higher frequency of previous admissions, ED visits, inpatient hospitalizations, ICU stays, intubations, chest X-rays, history of chronic sinusitis, gastroesophageal reflux disease, anxiety, and the use of tiotropium or a long-acting beta-agonist (LABA). Multivariable analysis confirmed that prior hospital admissions and a history of GERD are the strongest predictive factors for early asthma readmissions, yet a history of environmental allergies might be a protective factor (p = 0.053). CONCLUSIONS: Non-allergic asthma patients with multiple prior admissions, ED visits and inpatient hospitalizations, on multiple medications with history of GERD, sinusitis, and anxiety are more likely to be readmitted within 30 days irrespective of other factors. Patients with these characteristics should be assessed for interventions in an effort to reduce early readmissions.

Efficacy of Different Medical Therapies for the Treatment of Acute Laryngeal Attacks of Hereditary Angioedema due to C1-esterase Inhibitor Deficiency.

BACKGROUND: Hereditary angioedema (HAE) is a rare disease characterized by C1-esterase inhibitor (C1-INH) deficiency, resulting in periodic attacks of acute edema, which can be life-threatening if they occur in the upper airway. No head-to-head comparisons of different treatment options for acute HAE attacks are available. Because immediate symptom relief is critical for potentially life-threatening laryngeal attacks, it is important to determine the treatment option that provides optimal treatment response. OBJECTIVE: Review and compare data from clinical studies that evaluated the efficacy and safety of treatments for laryngeal HAE attacks. METHODS: We conducted an indirect comparison of clinical outcomes from prospective studies for treatment of 881 acute laryngeal attacks with plasma-derived C1-INH concentrate (pdC1-INH) at fixed doses (500 or 1000 U) or a body weight-adjusted dose (20 U/kg), recombinant C1-INH concentrate at a fixed dose (2100 U), or a body weight-adjusted dose (50 U/kg), icatibant (30 mg), or ecallantide (30 mg). Comparisons included time to onset of symptom relief and need for re-dosing or emergency procedures. RESULTS: The median time to onset of symptom relief ranged between 15 min and approximately 2 h, and was shortest with body weight-adjusted doses of pdC1-INH. The proportion of laryngeal attacks with re-dosing ranged between 0% and 72%. No re-dosing was needed after treatment with a single body weight-adjusted dose of pdC1-INH (48 attacks). CONCLUSIONS: Available data suggest that among different HAE treatments, body weight-adjusted pdC1-INH (20 U/kg) provides the most reliable treatment response for treatment of laryngeal HAE attacks.

Plasma-derived C1-INH for managing hereditary angioedema in pediatric patients: A systematic review.

Presently, medications approved for children with Hereditary Angioedema (HAE) are extremely limited. This is especially the case for children under 12 years of age. For this reason we reviewed and summarized the data on treatment of children with HAE. Available data indicate that plasma derived C1-inhibitor is a safe, effective treatment option for HAE in pediatric patients, including those below 12 years of age. Other therapies are also appear safe for the under 12 year of age, but less data are available. Importantly, home-based treatment of HAE in this age group appears to be safe and effective and can improve quality of life. These findings support current HAE consensus guidelines which strongly recommend the use of plasma derived C1-inhibitor as a first-line treatment in children and encourage home and self-treatment.