In addition to a wide range of case reports, reviews, and small series, here are summaries of recently published HAE-related scientific papers. Data search undertaken 9 October 2025. The source used is the National Library of Medicine (NLM). Due to a lapse in Government funding at the time of the search, the NLM may not be up to date. Any omissions will be captured in the next Global Perspectives.
Plasma kallikrein inhibitors for multiple disorders: Current advances and perspectives
Haonan Liu, et al
Writing in the Journal of Medicinal Chemistry, the authors analyse the biological functions of plasma kallikrein, its role in diseases such as HAE, and the potential of new treatments that target the kallikrein system.
(Journal of Medicinal Chemistry, 2 October 2025)
Observations on quality of life and disease control in patients with hereditary angioedema
Thomas Buttgereit, et al
Writing in Skin Health and Disease, the authors present data on how reducing the burden of treatment in HAE can positively impact quality of life. They conclude that treatment with lanadelumab can be individualized to suit patients while maintaining disease control and quality of life.
(Skin Health and Disease, July 2025)
A national survey of four decades of hereditary angioedema prophylaxis: Efficacy and safety of old and new drugs
Hanga Réka Horváth, et al
The authors examine a registry of Hungarian HAE patients to assess changes in treatment options and the safety of the medicines used. They conclude that the use of modern prophylaxis is increasing among Hungarian HAE patients, following global trends. Both modern and traditional long-term prophylaxis (LTP) options proved to be safe and effective when used in conjunction with appropriate monitoring.
(Clinical Immunology, October 2025)
Measurement of cleaved high-molecular-weight kininogen in patients with hereditary angioedema due to C1-inhibitor deficiency: Preanalytical and analytical optimization
Chiara Suffritti, et al
The authors are working to identify methods that allow for the stable measurement of high-molecular-weight kininogen (HK) as a diagnostic test for HAE attacks. The authors found that when measuring cleaved HK in plasma from patients with C1-inhibitor deficiency, the use of anticoagulant with protease inhibitors and precast gels allows reliable evaluation of in vivo contact system activation.
(Journal of Immunological Methods, 30 September 2025)
Population-scale analysis reveals germline loss of SERPING1 (C1-Inhibitor) is a polyphenotypic thrombotic disorder
Alfonso Rodriguez Espada, et al
The authors present research that more clearly associates SERPING1 with thrombosis (blood clots in the circulation system). Results from over 600,000 HAE patients showed that thrombosis was as likely as HAE due to C1-inhibitor deficiency in individuals who lack the SERPING1 gene.
(Blood Advances, 30 September 2025)
First report from the Czech national registry of inborn errors of immunity (2012-2025)
Zita Chovancova, et al
The authors present the first comprehensive report of inborn errors of immunity in Czechia. Of 1,443 registered patients, 222 had a diagnosis of HAE. This was 15.4% of the total. Overall, the authors indicate that the prevalence of inborn errors of immunity in the Czech Republic is approximately 13.2 per 100,000.
(Frontiers of Immunology, 15 September 2025)
A Phase-1 randomized study: Garadacimab pharmacokinetics, safety, and tolerability after administration via autoinjector/pre-filled pen versus pre-filled syringe in healthy participants
Fiona Glassman, et al
The group examined various aspects of treatment with garadacimab, and the use of an autoinjector/pre-filled pen or pre-filled syringe. The authors conclude that using an autoinjector or pre-filled pen resulted in consistent safety and tolerability compared to administration via a pre-filled syringe. These findings support the administration of garadacimab through an autoinjector or pre-filled pen, which may be a convenient at-home option for patients and physicians.
(The Journal of Clinical Pharmacology, 6 September 2025)
Lanadelumab’s impact on hereditary angioedema control and quality of life across disease activity subgroups: Real-world evidence
Andrea Zanichelli, et al
The authors used real-world data to examine the longer-term effectiveness of lanadelumab in individuals with HAE who had varying attack rates before starting treatment (baseline disease activity rate). The authors found that in patients treated with lanadelumab, the attack rates were low, and patients experienced improvements in health-related quality of life and disease control, regardless of their baseline disease activity. Overall, the authors feel these findings support long-term prophylaxis with lanadelumab across disease activity levels.
(Annals of Allergy, Asthma and Immunology, 6 August 2025)
Status quo and future developments in the diagnosis and treatment of hereditary angioedema
Andreas Recke
Writing in the German journal, Journal der Deutschen Dermatologischen Gesellschaft, the author reviews the clinical presentation, diagnosis, and treatment of HAE.
(Journal der Deutschen Dermatologischen Gesellschaft, 4 September 2025)
Insights from the first 820 patients from the Brazilian multicenter registry of hereditary angioedema: The key role of genetic testing and targeted therapies
Mariana PL Ferriani, et al
The authors aimed to identify knowledge gaps among healthcare professionals that may be hindering patient care in Brazil. In conclusion, they found that Brazilian patients with HAE share common aspects with global patients, including predominance in women, and HAE-C1INH as the most common subtype. Available genetic testing enabled the identification of a notable proportion of HAE-FXII (19.4% of patients). Despite recent advances, access to first-line therapies for long-term prophylaxis of HAE attacks remains limited.
(The Journal of Allergy and Clinical Immunology: In Practice, 3 September 2025)
C1-inhibitor: From complement system to bradykinin angioedema
Federica Defendi, et al
This review aims to provide a comprehensive overview of the structure, regulation, and biological functions of C1INH, its role in physiological and pathological processes — particularly in angioedema — as well as current and emerging diagnostic and therapeutic strategies. Special emphasis is placed on the molecular mechanisms linking C1INH deficiency or dysfunction to disease, as well as recent progress in precision medicine.
(Current Opinion in Immunology, 3 September 2025)
Quality of life and burden of disease in patients with hereditary angioedema and their caregivers
Donald S Levy, et al
The authors examined the various ways in which HAE affects the quality of life for patients and caregivers. They conclude that HAE continues to substantially impact the quality of life of patients. They call for additional research to confirm how individual factors such as patient age, sex, and HAE type affect quality of life.
(Allergy and Asthma Proceedings, 1 September 2025)
Real-world treatment patterns and burden-of-disease of sub-optimally controlled hereditary angioedema
Henriette Farkas, et al
The authors investigated the impact of poorly controlled HAE on the quality of life of patients. They found that, on average, patients with uncontrolled HAE had just under 10 attacks (9.9) per year. They found that the quality of life worsened as attack rates increased. They concluded that sub-optimal disease control in HAE is associated with the use of only on-demand therapy. Poorly controlled HAE has a serious burden on the lives of patients, especially in those with frequent attacks and in women.
(World Allergy Organizations Journal, 1 September 2025)
Revealing hidden patterns in hereditary angioedema
Chun-Chieh Chen and Shiuan-Chih Chen
The authors respond to a recent study of the prevalence of HAE in the USA. They suggest that the study highlights disparities in diagnosis and treatment that warrant further scrutiny.
(Annals of Allergy, Asthma and Immunology, September 2025)
Donidalorsen treatment of hereditary angioedema in patients previously on long-term prophylaxis
Marc A Riedl, et al
The authors provide an interim report on the safety, efficacy, quality of life (QoL), and treatment preference and satisfaction from a trial of donidalorsen for HAE. The authors conclude that donidalorsen was well tolerated, decreased HAE attack rate, and improved QoL and disease control. Most patients preferred donidalorsen over their prior treatment. Further analyses are planned at week 52.
(Journal of Allergy and Clinical Immunology: In Practice, September 2025)
Treatment patterns and characteristics of patients with hereditary angioedema treated with lanadelumab: A US retrospective chart review
Maureen Watt, et al
A team from Takeda, the pharmaceutical company behind lanadelumab, looked at the types of patients receiving the treatment in the US. They conclude that lanadelumab dosing intervals can be individualized to maintain effective disease control. A dosing interval extension may be considered in well-controlled disease.
(Drugs – Real World Outcomes, September 2025)
Long-term safety and efficacy of once-daily berotralstat in patients with hereditary angioedema: APeX-S final results
Henriette Farkas, et al
The authors report the final results of a trial examining the safety and effectiveness of berotralstat in treating HAE in the long term. 387 patients received berotralstat during the trial, for an average duration of 48 weeks. The authors conclude that the study supports the long-term safety and efficacy of beroltralstat in preventing HAE attacks and improving quality of life.
(Annals of Allergy, Asthma and Immunology, September 2025)
Substitution of reactive centre loop residues from C1 esterase inhibitor increases the inhibitory specificity of alpha-1 antitrypsin for plasma kallikrein
Sangavi Sivananthan, et al
Writing in the Journal of Biotechnology, the authors describe their work to develop a more effective inhibitor of plasma kallikrein, as C1-inhibitor is slow to act.
(Journal of Biotechnology, September 2025)
Establishing a hereditary angioedema prevalence for the United States using a large administrative claims database
Anthony J Castaldo, et al
A team from the US Hereditary Angioedema Association (HAEA) and scientific colleagues worked to better establish the prevalence of all types of HAE in the United States. The results indicate that real-world estimates of HAE (all types) prevalence are greater than the 2 per 100,000 that is frequently cited for HAE-C1INH. Data from 2020 indicated 2.43 cases of HAE (all types) per 100,000 of population.
(Annals of Allergy, Asthma and Immunology, September 2025)
Long-term safety and effectiveness of sebetralstat: Interim analysis of KONFIDENT-S open-label extension
Henriette Farkas, et al
A large group of international HAE experts worked to evaluate the long-term safety and effectiveness of sebetralstat, an oral treatment for HAE attacks. The authors noted that poor compliance with hereditary angioedema guidelines for on-demand treatment is common due to challenges with injection administration. The authors concluded that oral sebetralstat enabled compliance with treatment guidelines, there were no new safety concerns, and the effectiveness of the medicine was maintained for repeated attacks.
(Journal of Allergy and Clinical Immunology: In Practice, 29 August 2025)
Evaluating functional C1INH with multiple laboratory methods across hereditary angioedema types
Maine Luellah Demaret Bardou, et al
This study evaluated a variety of laboratory methods used to check the function of C1-inhibitor in patients with suspected HAE. The authors concluded that dry blood spot and ELISA-based tests offered the potential for early diagnosis.
(Frontiers in Immunology, 26 August 2025)
Garadacimab in hereditary angioedema due to normal C1INH with F12/PLG mutations
Danny M Cohn, et al
This research explored how well garadacimab works as long-term prophylaxis in patients with HAE due to rare mutations, Factor XII and plasminogen. The authors found that whilst garadacimab only led to mild to moderate side effects in these patients, the efficacy was variable. 2 out of 3 patients with FXII mutation saw some benefit from garadacimab treatment; only 1 in 3 patients with plasminogen mutation saw a reduction in attack rates.
(Journal of Allergy and Clinical Immunology, 26 August 2025)
Expanding the genetic and clinical spectrum of hereditary angioedema with normal C1-inhibitor: Novel variants and treatment insights
Haiqing Gao, et al
The authors conducted an in-depth genetic analysis of 27 patients with HAE, including 8 with HAE with normal C1-inhibitor levels. They identified 4 previously unreported mutations of the MYOF gene, as well as other variants of KNG1 and HS3ST6. The HS3ST6 mutation led to treatment-resistant angioedema with persistent swelling in the feet and toes. The study indicated that treatment with lanadelumab reduced attack frequency in most patients; however, this effect was variable and required individualized treatment options, the authors suggested.
(Journal of Clinical Immunology, 23 August 2025)
One-year real-life outcomes of lanadelumab therapy in Romanian patients with hereditary angioedema due to C1-inhibitor deficiency
Noémi Anna Bara, et al
This research followed 24 Romanian patients during their first year of treatment with lanadelumab. The authors concluded that lanadelumab provided effective disease control and significantly improved quality of life in patients with HAE-C1INH over the course of 1 year. They encourage the use of regular evaluations, using validated questionnaires, to aid in assessing patients and monitoring treatment effectiveness.
(Frontiers in Allergy, 21 August 2025)
Characteristics and comorbidities influencing mortality risk among hereditary angioedema patients
Subhan Khalid and Alan T Hitch
The authors used statistical analysis to find out if certain patient characteristics or other diseases might increase the risk of death in people with HAE. The study showed that in the United States, older HAE patients and those who also had autoimmune conditions, hypertension, or low income were at higher risk of dying. The risk was raised in certain racial groups, insurance types, and income levels. In particular, older black patients from the Midwest of America exhibited the highest estimated mortality risk.
(Journal of Health Economics and Outcomes Research, 21 August 2025)
Effect of fresh frozen plasma infusion on hospital length of stay for patients with hereditary angioedema
Subhan Khalid and Alan T Hitch
The study examined the use of fresh frozen plasma to treat US patients with HAE. In its conclusions, the authors recommend caution when planning to use fresh frozen plasma, emphasizing the need to understand the underlying patient conditions and risk factors. They also recommend prioritizing C1-inhibitor therapy over fresh frozen plasma.
(Journal of Health Economics and Outcomes Research, 9 July 2025)
A single-centre retrospective study on the clinical characteristics of patients with hereditary angioedema and the therapeutic effect of lanadelumab
Yanhua Xu and Yinshi Guo
This study aimed to learn more about HAE in Chinese patients and the efficacy and safety of prophylactic treatment with lanadelumab. The authors followed 22 patients and felt able to conclude:
- Although many characteristics were similar to previous reports on Chinese patients with HAE, they found more HAE Type 2 patients than prior reports, and a trend towards earlier diagnosis in younger patients.
- After treatment with lanadelumab, patients experienced significant improvements in symptoms, quality of life, and anxiety/depression levels.
(Orphanet Journal of Rare Diseases, 18 August 2025)
Impact of providing education on the recognition and differential diagnosis of angioedema among emergency department physicians
Derya Unal, et al
This study assessed the knowledge of emergency room physicians and evaluated a training program on angioedema. The authors conclude that knowledge levels increased by a ‘remarkable’ amount after training, having initially been ‘inadequate’. They conclude that a training program should include the recognition of rare types of angioedema, with a particular emphasis on HAE disease.
(World Allergy Organization Journal, 9 August 2025)
Impact of hereditary angioedema attacks on health-related quality of life and work productivity
Maeve O’Connor, et al
This study focuses on the impact of HAE attacks on quality of life, work productivity, and well-being during and after HAE attacks. The authors concluded that late-treated and untreated attacks were associated with reduced health-related quality of life and work productivity. The negative impact of attacks may be reduced by increasing compliance with HAE guidelines (i.e., considering on-demand treatment for all attacks and treating as soon as possible), and by addressing barriers to on-demand therapy in general and early treatment in particular.
(World Allergy Organization Journal, 28 July 2025)
Bradykinin measurement by liquid chromatography tandem mass spectrometry in subjects with hereditary angioedema enhanced by cold activation
Jinguo Chen, et al
The authors explored new ways to measure bradykinin effectively. They used a method that subjected blood samples to cold to activate bradykinin. They conclude that this method worked well and could be the basis for a tool in the diagnosis and management of HAE.
(Journal of Allergy and Clinical Immunology Global, June 2025)
Sustained effectiveness, tolerability, and safety of long-term prophylaxis with lanadelumab in hereditary angioedema: The prospective, phase 4, noninterventional EMPOWER real-world study
Jonathan A Bernstein, et al
The authors presented data from a real-world research study of US and Canadian HAE patients treated with lanadelumab. They conclude that the study, called EMPOWER, demonstrated a marked reduction in HAE attack rate after patients started taking lanadelumab, and this low attack rate was maintained for the length of the study (up to 36 months). The authors also expressed confidence that no new safety issues were identified.
(Advances in Therapy, August 2025)
Hypertension risk in patients having hereditary angioedema with plasminogen gene mutation K330E
Konrad Bork, et al
The authors state that patients with HAE have an increased risk of developing high blood pressure due to the plasminogen gene mutation p.K330E. This is most notable in younger patients (aged 50 years or younger). The authors recommend regular blood pressure monitoring for these patients.
(Journal of Allergy and Clinical Immunology, August 2025)
Global frequency, diagnosis, and treatment of hereditary angioedema with normal C1-inhibitor
Markus Magerl, et al
A very large, multinational group of HAE experts worked to establish the prevalence, methods of diagnosis, and current treatment of HAE with normal C1-inhibitor (HAE-nC1INH). They conclude that HAE-nC1INH may be more prevalent than previously reported, and that existing methods of diagnosis and treatment are variable. They call for diagnostic tests and treatment options to be studied to improve the management of the condition.
(Journal of Allergy and Clinical Immunology: Global, February 2025)
Patient-reported outcomes in the phase III OASIS-HAE study of donidalorsen for hereditary angioedema
Marc A Riedl, et al
As part of the OASIS-HAE trial of donidalorsen to treat HAE, patients were asked about their quality of life and how well their disease is controlled. This study details the findings on these patient-reported outcomes. The authors conclude that donidalorsen significantly improved quality of life and other patient-reported outcomes compared to placebo.
(Allergy, August 2025)
Hereditary angioedema (HAE) in China: Advancing awareness, access, advocacy and alliances from the Greater Bay Area to the global HAE community
Philip H Li, et al
The article offers an overview of the progress in managing Hereditary Angioedema (HAE) in China, with a specific focus on the Greater Bay Area (GBA). The authors believe that by uniting as a global community, significant advances can be made in the lives of people with HAE.
(Clinical and Experimental Allergy, August 2025)
Clinical presentation and management of 239 children and adolescents with hereditary angioedema
Peter D Arkwright, et al
The authors studied 239 British children and adolescents with hereditary angioedema. Key findings presented were:
- Only 2% experienced 1 or more attacks a month
- The disease was most prominent in adolescent girls, who were 4 to 5 times more likely to have skin swelling and abdominal pain, and 7 times more likely to take time off from school than were girls aged less than 12 years
The authors highlight that hereditary angioedema disproportionately affects the quality of life and education of adolescent girls.
(Journal of Allergy and Clinical Immunology: In Practice, 29 July 2025)
Unmet needs in hereditary angioedema: An international survey of physicians
Thomas Buttgereit, et al
This large, multinational group of researchers surveyed physicians from across the ACARE network about unmet needs and barriers to optimal management in HAE. The authors call for action to improve access to treatments, for greater provision of education for physicians and patients, critical collaboration with patient organizations and industry stakeholders, and ultimately to optimize HAE care.
(Orphanet Journal of Rare Diseases, 28 July 2025)
Proactive identification of rare diseases: Lessons from hereditary angioedema diagnosis using electronic medical records
Xue Wang, et al
This study suggests that, rather than patients seeking physicians when they may have a rare disease, physicians should actively identify potential patients, and that this is possible by utilizing electronic medical records (EMRs). By analyzing medical records, the authors identified and subsequently diagnosed 3 new cases of HAE.
(Orphanet Journal of Rare Diseases, 28 July 2025)
Oral berotralstat for hereditary angioedema prophylaxis in patients aged 2 to <12 years: APeX-P interim results
Jolanta Bernatoniene, et al
This clinical trial evaluated the effectiveness of berotralstat, administered as a pill, in pediatric patients with HAE. The authors were able to conclude that oral berotralstat was well-tolerated and resulted in early and sustained reductions in HAE attack rate.
(Annals of Allergy, Asthma and Immunology, 25 July 2025)
Disease control and disease activity in hereditary angioedema: Two sides of the same coin?
Behzad Heibati, et al
These authors wished to find out how much overlap there was between commonly used questionnaires: the Angioedema Control Test (AECT) and Hereditary Angioedema Activity Score (HAE-AS). The authors conclude that using both in clinical practice can provide a more comprehensive patient evaluation.
(Frontiers in Immunology, 22 July 2025)
Long-term real-world outcomes in patients with hereditary angioedema receiving lanadelumab for 3 or more years
William R Lumry, et al
The authors examined the medical records of 51 patients with HAE in the US and assessed the effect of receiving lanadelumab on their quality of life. The findings show that quality of life increased with treatment, and that there were also improvements in attack frequency and disease severity.
(International Archives of Allergy and Immunology, 17 July 2025)
Delays and barriers related to the treatment of hereditary angioedema attacks in Italy
Mauro Cancian, et al
The authors, writing in a research letter, suggest that numerous barriers contribute to on-demand treatment delays. These issues could be addressed by educating patients on the importance of complying with treatment guidelines and enhancing awareness of early attack symptoms. They suggest that a primary barrier to early treatment is the need to use an injectable medicine, and that an oral on-demand treatment may ease the burden for patients, healthcare systems, and carers.
(Allergy, 16 July 2025)
Consensus on diagnosis and management of hereditary angioedema in Greece
AE Germenis, et al
With numerous advances in the diagnosis and treatment of HAE, the Hellenic Society of Angioedema has worked to develop consensus recommendations for the diagnosis, treatment, and management of hereditary angioedema. The resulting consensus included statements that were agreed upon by more than 80% of the experts. The authors outline the 24 consensus recommendations that were finally formulated.
(European Annals of Allergy and Clinical Immunology, 2 July 2025)
The determinants of angioedema attacks related to dental and gingival procedures in hereditary angioedema patients
Nihal M Gokmen
This research examined the factors that cause acute HAE attacks during dental procedures. The authors found that prophylactic HAE treatment significantly reduced the frequency of attacks compared to an untreated group. This is especially important, they say, for patients with higher attack frequency, lower C1-inhibitor function, and women. High-risk dental procedures included tooth extractions, such as wisdom tooth extractions.
(BMC Oral Health, 2 July 2025)
Activation of the complement/lectin pathway, angiopoietin/tie-2/VEGF-System, cytokines and chemokines in different angioedema subtypes
Katharina Marlies Duda, et al
The molecular changes and interactions that take place during HAE attacks are not well understood. This study investigates some new methods of looking at biomarkers in the bodies of people with HAE.
(European Journal of Immunology, July 2025)
Evaluating large language models for WAO/EAACI guideline compliance in hereditary angioedema management
Mehmet Emin Gerek, et al
The authors tested several common artificial intelligence models (such as ChatGPT) on their responses to questions about HAE and how well these aligned with the latest guidelines on HAE. They found that ChatGPT and Gemini were more adherent to the guidelines than other AI tools. However, they suggest that inconsistencies mean more work is needed to enhance their reliability for medical applications.
(Allergogia et Immunopathologia, 1 July 2025)
Hereditary angioedema treatment beyond biologics: Current state of preventive and on-demand approaches and new perspectives
Andrea Zanichelli, et al
The authors reviewed the state-of-the-art of HAE preventive and on-demand treatment of non-biologic drugs. In their expert opinion, all HAE patients should have an on-demand treatment to manage attacks, with long-term prophylaxis considered and evaluated every time the patient visits their healthcare provider. The authors believe oral treatments may address the practical needs of patients, reducing treatment burden and improving quality of life.
(Expert Opinion on Pharmacotherapy, July 2025)
The potential of factor XII inhibitors in preventing hereditary angioedema attacks
James KY Looi, et al
The authors review the role of Factor XII in HAE and how addressing it may offer a treatment strategy. They highlight the potential of Factor XII inhibitors and how garadacimab validated the concept, but raise the need for more research to answer questions around long-term safety, cost, and accessibility.
(Expert Opinion on Pharmacotherapy, July 2025)
Safety and pharmacokinetics of long-acting plasma kallikrein inhibitor navenibart (STAR-0215) in healthy adults
William Lumry, et al
Before medicines are investigated in people with the condition they aim to help, they are routinely tested on healthy volunteers to determine their effects on the human body. In this study, the authors trialled a potential new HAE medicine, called navenibart (previously STAR-0215), in 31 healthy volunteers. They conclude that the medicine was well-tolerated and had an extended half-life, which may support more infrequent dosing of this treatment.
(Annals of Allergy, Asthma and Immunology, July 2025)