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.

Impact of Sulfonamide Allergy Label on Clinical Outcomes in Patients with Pneumocystis jirovecii Pneumonia.

INTRODUCTION: The presence of antibiotic allergy labels can have harmful impacts on clinical outcomes, particularly among immunosuppressed patients, in whom there have been associations with increased complications, readmission rates, and mortality. We explore the effects of a sulfonamide allergy label (SAL) on clinical outcomes in adult patients with Pneumocystis jirovecii pneumonia (PJP). METHODS: In this retrospective matched cohort study, we utilized TriNetX, a multicenter national database, to match 535 adult patients with PJP and SAL to an equal number of controls. We identified cases indexed between 01/01/2010 and 01/01/2023 utilizing ICD-10 codes for PJP and allergy status to sulfonamides and through detection of P. jirovecii antigen with immunofluorescence or PCR. Propensity score matching was performed in a 1:1 fashion for demographics and comorbidities, and our analysis included clinical outcomes that occurred within 30 days after the occurrence of the index event. RESULTS: While hospitalization risk tended to be lower among patients with SAL as compared to controls (RR: 0.90; 95% CI 0.81-1.01), there were no major differences in the risk of respiratory failure (RR: 0.94; 95% CI 0.84-1.05), prednisone use (RR: 1; 95% CI 0.91-1.10), intensive level of care requirement (RR: 0.85; 95% CI 0.69-1.06), intubation (RR: 0.85; 95% CI 0.61-1.19), or mortality (RR: 0.98; 95% CI 0.68-1.42). The presence of SAL did however impact antibiotic prescription patterns, with an underutilization of trimethoprim (RR: 0.50; 95% CI 0.43-0.59) and sulfamethoxazole (RR, 0.47; 95% CI 0.40-0.56) and overuse of alternative agents by patients with SAL as compared to controls. Yet, there was no difference in the occurrence of adverse outcomes such as hepatotoxicity (RR: 1.09; 95% CI 0.49-2.45) or acute kidney injury (RR: 0.94; 95% CI 0.78-1.14) between patients with SAL and controls. CONCLUSIONS: The presence of SAL alters antibiotic prescription patterns among adults with Pneumocystis infection but has no clinically significant impact on outcomes.

Garadacimab for hereditary angioedema attack prevention: long-term efficacy, quality of life, and safety data from a phase 2, randomised, open-label extension study.

BACKGROUND: Garadacimab is a fully human immunoglobulin G4 monoclonal antibody targeting activated factor XII. This study evaluated long-term efficacy, health-related quality of life (HRQoL), and safety data for garadacimab in adults with hereditary angioedema. METHODS: This global phase 2 study comprised a treatment period 1 (TP1: 12 weeks, double-blind, placebo-controlled) and a treatment period 2 (TP2: ≥44-week open-label extension). Patients aged 18-65 years with clinically confirmed hereditary angioedema were eligible. In TP1, 32 patients were randomly assigned (1:1:1:1) to receive subcutaneous garadacimab (75 mg, 200 mg, or 600 mg) or placebo every 4 weeks (once monthly). Randomisation was done using interactive response technology via block randomisation (block sizes 1-4). Subsequently, six additional patients in TP1 were assigned to open-label garadacimab 400 mg every 2 weeks. At the start of TP2, patients were re-randomised (if receiving placebo, garadacimab 75 mg, or garadacimab 400 mg) or continued to receive garadacimab 200 mg or garadacimab 600 mg once monthly. After a protocol amendment on March 20, 2020, patients originally assigned to the 600 mg dose were down-titrated to 200 mg at their next visit. The primary endpoint (published previously) was monthly attack rate for patients receiving 200 mg or 600 mg garadacimab in TP1 in the intention-to-treat population. Here, we assessed the impact of garadacimab on patient-reported and investigator-reported outcomes and HRQoL as well as long-term efficacy and safety. This trial is registered with ClinicalTrials.gov, NCT03712228, and is completed. FINDINGS: Of 54 patients screened between Oct 29, 2018, and Aug 28, 2019, 32 randomised and six open-label patients completed TP1 and entered TP2 (20 in the garadacimab 200 mg group; 18 in the garadacimab 600 mg group; total 38 patients). Median age was 39·0 years (IQR 27·0-53·0), and 21 patients (55%) were female and 17 (45%) were male. In TP2, the median garadacimab exposure was 87·9 weeks (IQR 50·0-106·6) in the garadacimab 200 mg group and 44·1 weeks (24·1-56·1) in the garadacimab 600 mg group. Median monthly attack rates were 0·0 (IQR 0·0-0·1) in the garadacimab 200 mg group and 0·1 (0·0-0·4) in the garadacimb 600 mg group. Median reduction in monthly attack rate versus run-in was 100% (IQR 98-100) with garadacimab 200 mg. HRQoL improvements observed during TP1 with garadacimab were sustained throughout TP2. TP2 safety signals were consistent with TP1. Two patients experienced serious adverse events of diverticular perforation and asthma (not garadacimab-related). Treatment-emergent adverse events were mostly mild or moderate in severity. The most common adverse events were headache (nine of 38, 24%) and abdominal pain (seven of 38, 18%). There were no treatment-related deaths. INTERPRETATION: Once-monthly garadacimab for more than 2 years in patients with hereditary angioedema was well tolerated and efficacious in reducing monthly attack rate and improving HRQoL. These results reveal the potential of long-term prophylactic treatment with 200 mg once-monthly garadacimab towards complete disease control of patients with hereditary angioedema. FUNDING: CSL Behring.

Comparative Impact of Asthma Biologics: A Nationwide US Claim-Based Analysis.

BACKGROUND: Biologic modifiers targeting type 2 (T2) airway inflammation are effective in reducing asthma exacerbation. However, real-world and comparative effectiveness studies remain limited. OBJECTIVE: To examine and compare the real-world impact of anti-T2 asthma biologics. METHODS: In this retrospective, new user cohort study, we used the MarketScan, a Commercial Claims and Encounters Database, to identify adult patients with asthma who began to receive an anti-T2 biologic agent (anti-IL-5s, dupilumab, or omalizumab). We examined the influence of the biologic class on asthma exacerbation by comparing the average number of asthma exacerbation 1 year before and after biologic initiation. We conducted multivariable regression analyses to compare the effectiveness of these asthma biologics on reducing the incidence of asthma exacerbations within 18 months of the initial administration of biologics while controlling for demographic variables, comorbidities, and asthma severity. RESULTS: We identified 5,538 asthma patients who were new to taking an anti-T2 biologic [mean age [±SD], 45.6 (12.78) years; 65.8% female). Asthma biologics reduced asthma exacerbation by 11% to 47%, particularly among patients with two or more asthma exacerbations in the year preceding biologic initiation (31% to 65% reduction). Biologics were especially effective in reducing asthma-related hospitalizations (44.6% to 60%). After adjusting for baseline demographics, asthma medication, and comorbidities, dupilumab was associated with a lower estimated mean number of asthma exacerbation per year and lower adjusted odds ratio for developing an asthma exacerbation relative to other biologics (50% to 80% less likely). CONCLUSIONS: Anti-T2 asthma biologics reduced asthma exacerbation in real-word settings. Evidence supports growing literature reporting that dupilumab might have a more favorable impact on asthma exacerbation relative to other asthma biologics.

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.

Artificial Intelligence-Generated Scientific Literature: A Critical Appraisal.

BACKGROUND: Review articles play a critical role in informing medical decisions and identifying avenues for future research. With the introduction of artificial intelligence (AI), there has been a growing interest in the potential of this technology to transform the synthesis of medical literature. Open AI's Generative Pre-trained Transformer (GPT-4) (Open AI Inc, San Francisco, CA) tool provides access to advanced AI that is able to quickly produce medical literature following only simple prompts. The accuracy of the generated articles requires review, especially in subspecialty fields like Allergy/Immunology. OBJECTIVE: To critically appraise AI-synthesized allergy-focused minireviews. METHODS: We tasked the GPT-4 Chatbot with generating 2 1,000-word reviews on the topics of hereditary angioedema and eosinophilic esophagitis. Authors critically appraised these articles using the Joanna Briggs Institute (JBI) tool for text and opinion and additionally evaluated domains of interest such as language, reference quality, and accuracy of the content. RESULTS: The language of the AI-generated minireviews was carefully articulated and logically focused on the topic of interest; however, reviewers of the AI-generated articles indicated that the AI-generated content lacked depth, did not appear to be the result of an analytical process, missed critical information, and contained inaccurate information. Despite being provided instruction to utilize scientific references, the AI chatbot relied mainly on freely available resources, and the AI chatbot fabricated references. CONCLUSIONS: The AI holds the potential to change the landscape of synthesizing medical literature; however, apparent inaccurate and fabricated information calls for rigorous evaluation and validation of AI tools in generating medical literature, especially on subjects associated with limited resources.

Improving Detection of Alpha-1 Antitrypsin Deficiency: Role of the Allergist.

Alpha-1 antitrypsin deficiency (AATD) is a genetic disorder that manifests as lung and/or liver disease. Because symptoms of AATD overlap with those of common pulmonary and hepatic conditions, AATD is often misdiagnosed, which has resulted in substantial underdiagnosis of AATD worldwide. Although screening patients for AATD is recommended, the lack of procedures to facilitate testing remains a barrier to accurate diagnosis of AATD. Delays in AATD diagnosis can worsen outcomes for patients by postponing appropriate disease-modifying treatments. Patients with AATD-related lung disease experience symptoms similar to other obstructive lung disorders and are often misdiagnosed for years. In addition to existing screening guidelines, we recommend that screening for AATD become a standard part of allergists' workups of patients with asthma and fixed obstructive disease, chronic obstructive pulmonary disease, bronchiectasis without known origin, and patients under consideration for treatment with biologics. This Rostrum article reviews screening and diagnostic tests available in the United States and emphasizes evidence-based strategies to increase testing frequency and improve AATD detection rates. We underscore the pivotal role of allergists in managing care for patients with AATD. Finally, we urge health care providers to be aware of potentially poor clinical outcomes among patients with AATD during the coronavirus disease 2019 pandemic.

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.

Racial and Ethnic Disparities in Allergen Immunotherapy Prescription for Allergic Rhinitis.

BACKGROUND: Racial and ethnic differences exist in the severity of various atopic diseases including allergic rhinitis (AR). Patients of under-represented races and ethnicities may be subjected to disparate subcutaneous allergen immunotherapy (SCIT) prescription practices. OBJECTIVE: To explore the racial and ethnic disparities in the use of SCIT among patients with AR. METHODS: In this retrospective matched cohort study, we used the TriNetX US Collaborative Network, a multicenter electronic health record-based database to identify patients with AR 18 years and older. Patients were grouped according to their racial and ethnic identification. Study groups were matched for baseline demographics, atopic comorbidities, heart diseases and utilization of ß-blockers, and angiotensin-converting enzyme inhibitors. The proportion of patients of under-represented racial and ethnic groups started on SCIT was contrasted to the non-Hispanic White cohort. RESULTS: We identified 1,038,000 patients with AR; the mean age (±standard deviation) at the index was 49.7 (±16.1) years, and 64.6% were female. Ethnicity information was available from 87.3% of patients, and the majority (92.3%) were non-Hispanic. Over a 3-year observation period, fewer Black patients (relative risk [RR], 0.40; 95% confidence interval [CI], 0.33-0.48) and Hispanic patients (RR, 0.80; 95% CI, 0.64-0.99) were started on SCIT compared with non-Hispanic White patients. The proportions of Asian patients who were initiated on SCIT tended to be lower when compared with non-Hispanic White patients (RR, 0.69; 95% CI, 0.47-1.009). CONCLUSIONS: In the United States, differences in SCIT prescription exist between Black and Hispanic patients relative to White patients. Barriers to treatment should be explored and mitigated.

Effectiveness and safety of lanadelumab in ethnic and racial minority subgroups of patients with hereditary angioedema: results from phase 3 studies.

BACKGROUND: The COVID-19 pandemic has highlighted disparities in healthcare, particularly in the United States, even though disparities have existed since the organization of the modern healthcare system. Recruitment of patients from racial and ethnic minority groups is often minimal in phase 3 clinical trials, and is further exacerbated in the case of trials for rare diseases such as hereditary angioedema (HAE). This can lead to a gap in the understanding of minority patients' experiences with these diseases and their response to potential treatment options. METHODS: We reviewed data from phase 3 double-blind (HELP) and open-label extension (HELP OLE) trials of lanadelumab, a monoclonal antibody developed for long-term prophylaxis against attacks of HAE. Efficacy (attack rate reduction) and safety (adverse events) results from White patients were compared descriptively to those from Hispanic/Latino patients, Black/African Americans, and other minority Americans. RESULTS: Not surprisingly, few minorities were recruited across both studies: 9.5% Black, 2.4% Asian, and 7.1% Hispanic/Latino versus 88.1% White and 91.7% non-Hispanic/non-Latino received lanadelumab in HELP, and 4.7% Black, 0.9% Asian, 0.9% other, and 6.1% Hispanic/Latino versus 93.4% White and 93.4% non-Hispanic/non-Latino were enrolled in HELP OLE. Although these studies were conducted in the United States, Canada, Europe, and Jordan, all minorities were from the United States. Despite the number of minority patients being far less than expected for the population, there was no evidence that either efficacy or adverse event profiles differed between ethnic or racial groups. CONCLUSIONS: The HELP and HELP OLE studies described herein recruited far fewer minorities than would be ideal to represent these populations. However, evidence suggests that the effectiveness and tolerance of lanadelumab are similar between the groups. Nonetheless, the disparity in recruitment into research for minorities has significant room for improvement. Trial registration NCT02586805, registered 26 October 2015, https://clinicaltrials.gov/ct2/show/record/NCT02586805 . NCT02741596, registered 18 April 2016, https://clinicaltrials.gov/ct2/show/NCT02741596 .

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.

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.

Pulmonary Therapy Podcast-COVID-19: Research and Real-World Experiences from the Editorial Board.

The Editorial Board have prepared a podcast describing their experiences over the past year of the COVID-19 pandemic. The Editorial Board describe how COVID-19 impacted their research and how the initial clinical response changed over the course of the year in terms of treatment, personal protective equipment (PPE), and policy changes. The podcast and transcript can be viewed below the abstract of the online version of the manuscript. Alternatively, the podcast and transcript can be downloaded here: https://doi.org/10.6084/m9.figshare.14402291 Pulmonary Therapy Podcast-COVID-19: Research and Real-World Experiences from the Editorial Board (MP4 160260 KB).

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.

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.