In addition to a wide range of case reports and small series, here are summaries of recently published HAE-related scientific papers. Data search undertaken 3 October 2024.
Current and emerging therapeutics in hereditary angioedema
By Toan Do and Marc Riedl
The authors review the current and future landscape of treatment for HAE. In doing so, they make clear that the goal of HAE therapy is to normalize the patient’s life and ultimately achieve total control of the condition; shared-decision making is essential to reaching this goal. They tell the reader that effective on-demand HAE medication should be used as early as possible during an angioedema attack for optimal efficacy in treating HAE symptoms; delays in on-demand treatment are a common cause of HAE morbidity. Finally, they state that long-term prophylactic (LTP) medications are increasingly used to manage HAE due to improvements in efficacy.
(Immunology and Allergy Clinics of North America, August 2024)
Factor XII structure-function relationships
By Aleksandr Shamanaev, et al
The authors investigated how the structure of Factor XII impacted on its function in the body. The authors conclude that FXII circulates in blood in a “closed” form that is resistant to activation until interactions with other substances produced by the body. The authors believe that this will have implications for understanding how FXII contributes to diseases such as hereditary angioedema and for developing treatments.
(Seminars in Thrombosis and Hemostasis, October 2024)
Epidemiology, economic, and humanistic burden of hereditary angioedema: A systematic review
By Xin Guan, et al
The authors of this paper look to calculate the burden of HAE on patients’ lives. By reviewing available literature on 10,310 patients with HAE, they indicated substantial financial costs, mostly due to missing work and loss of productivity. The authors conclude that early diagnosis and improved awareness amongst healthcare professionals can reduce the burden of HAE on patients and society.
(Orphanet Journal of Rare Diseases, July 2024)
Systemic inflammation biomarkers during angioedema attacks in hereditary angioedema
By Johana Gil-Serrano, et al
The authors looked for biomarkers of inflammation in people undergoing an HAE attack. They found that inflammation may extend beyond the area of swelling, and that the involvement of inflammation pathways in HAE needs further investigation.
(Frontiers in Immunology, June 2024)
Long term outcome of C1-esterase inhibitor deficiency
By Luong Hoang Long, et al
The authors review the evidence on long-term outcomes for people living with HAE. They conclude that in any annual health survey, people with HAE should be assessed for autoimmune diseases, cancer, and other chronic illnesses. In patients being treated with androgens, tests should also include blood fats and liver examinations.
(Asian Pacific Journal of Allergy and Immunology, June 2024)
Hereditary angioedema prevalence and satisfaction with prophylaxis in South Australia
By Alexander Troelnikov, et al
The authors report a lack of population studies amongst Australian HAE patients. Undertaking their own research, the authors conclude that the prevalence of HAE in south Australia is in line with international reports. They also demonstrate that patients on long-term prophylaxis report these to be effective and are highly satisfied.
(The World Allergy Organization Journal, June 2024)
Classification, diagnosis and pathology of angioedema without hives
By Bruce Zuraw and Sandra Christiansen
The authors conclude here that being able to efficiently categorize and diagnose all forms of angioedema results in improved patient outcomes.
(Immunology and Allergy Clinics of North America, August 2024)
Prophylaxis in hereditary angioedema: a United Kingdom Delphi consensus
By Patrick FK Yong, et al
The authors, which include HAEi’s very own Rachel Annals, looked to update the current consensus amongst UK clinicians and patient advocates on how to prevent attacks in people with HAE in the UK. The key points from the resulting consensus statement were:
- UK access criteria for modern long-term prophylaxis based on numerical frequency of attacks alone are too simplistic and potentially disadvantage a cohort of patients who may benefit.
- Patients should be seen in expert centers, remote monitoring of patients is popular post-pandemic, and the use of patient-reported outcome measures can potentially improve patient care.
- Psychological health is an area in which patients may benefit, and recognition of this is important for future research and development.
Hereditary angioedema: The clinical picture of excessive contact activation
By Remy S Petersen, et al
Based on a review of existing data, the authors conclude that while C1-inhibitor is an important regulator in several intravascular pathways, symptoms in HAE patients are caused by insufficient inhibition of the contact activation pathway and kallikrein-kinin system. The subsequent unpredictable and potentially life-threatening angioedema attacks have a pronounced effect on quality of life. The authors note that new, highly specific therapies have the potential to enable patients to lead a normal life.
(Seminars in Thrombosis and Hemostatis, October 2024)
Hereditary angioedema: Beyond swelling
By Paul A Kyrle and Sabine Eichinger
Writing in the journal Blood, the authors provide an editorial linked to the article below. They discuss the evidence linking HAE with blood clots in the veins of the legs (VTE or venous thromboembolism). If this is the case, they argue, then patients should be considered for prophylactic C1INH treatment after an unprovoked VTE. All patients with HAE who suffer a provoked VTE should be treated the same as any other patient.
(Blood, July 2024)
Increased risk of venous thromboembolism in young and middle-age individuals with hereditary angioedema: A family study
By Linda Sundler Björkman, et al
The authors investigated families with HAE in Sweden, to see if there was any increased incidence of blood clots in the veins of these people. They found that these blood clots were associated with young and middle-aged individuals with HAE. They conclude by suggesting that HAE may be considered a new, rare, abnormal tendency towards blood clot formation.
(Blood, July 2024)
Deucrictibant for angioedema due to acquired C1-inhibitor deficiency: A randomized-controlled trial
By Remy S Petersen, et al
The authors conducted a small trial to see how safe and effective a potential new treatment for HAE, called deucrictibant, could be at treating and preventing HAE attacks in patients with acquired C1-inhibitor deficiency. The authors conclude that deucrictibant has the potential to effectively and safely treat and prevent angioedema attacks due to C1-inhibitor deficiency.
(Journal of Allergy and Clinical Immunology, July 2024)
Physician and patient-reported outcomes by hereditary angioedema type: Data from a real-world study
By John Anderson, et al
The authors asked patients and clinicians about the severity of their disease and the outcomes from treatment. They conclude that patients with HAE with normal C1 have increased disease activity and severity compared to those with HAE type I and type II, leading to greater impairment to their quality of life.
(Allergy and Asthma Proceedings, July 2024)
Contact system activation and bradykinin generation in angioedema: Laboratory assessment and biomarker utilization
By Sandra C Christiansen and Bruce L Zuraw
Proteins in the blood can, when released, lead to blood clotting and inflammation. When these proteins are produced incorrectly or not at all, this can cause diseases such as HAE. In this review, the authors explain the evidence that bradykinin generation underlies even HAE with normal C1INH.
(Immunology and Allergy Clinics of North America, August 2024)
An LNP-CRISPR gene editing drug demonstrates efficacy and safety in patients with hereditary angioedema following in-vivo administration
By Norbert Pardi and Zoltán Ivics
In an editorial reviewing the recent data published by a team led by Hilary Longhurst, the authors discuss the potential for gene-editing drugs to prevent HAE attacks in people living with the disease. They conclude that such drugs may offer the extraordinary perspective of treating severe genetic conditions with a single-dose, one-and-done treatment.
(The Journal of Allergy and Clinical Immunology, August 2024)
Inter-α-trypsin inhibitor heavy chain 4 (ITIH4) as a compensatory protease inhibitor in hereditary angioedema
By Anne Troldborg, et al
The authors state that nothing is known about the role of inter-α-trypsin inhibitor heavy chain 4 (ITIH4) in HAE despite its involvement in many pathways that lead to attacks. The authors conclude that ITIH4 may be valuable as a diagnostic and prognostic biomarker in HAE.
(The Journal of Allergy and Clinical Immunology, August 2024)
Targeting factor XIIa for therapeutic interference with hereditary angioedema
By Danny M Cohn and Thomas Renné
The authors state that targeting factor XIIa is emerging as an attractive option for disrupting HAE attacks. They conclude, following a review of the treatments currently being evaluated in clinical trials, that there may be potential advantages to targeting factor XIIa versus other targets in the kallikrein-kinin system.
(Journal of Internal Medicine, October 2024)
Centralized care model for hereditary angioedema overcomes geographical barriers
By Ashley Holmes, et al
The authors aimed to see if there were differences in care between HAE patients living in urban or rural settings. They conclude that in their practice (an ACARE center), rural patients received similar high-quality care, which they attribute to the centralized care model employed in which HAE patients in the region are seen at a single comprehensive care clinic.
(Frontiers of Immunology, July 2024)
Structural basis for the inhibition of βFXIIa by garadacimab
By Ieva Drulyte, et al
The authors examined the structure of the potential HAE treatment garadacimab, using an electron microscope. They found garadacimab strikingly similar to true factor XIIa inhibitors such as C1 inhibitor.
(Structure, July 2024)
Hereditary angioedema: 24 years of experience in a Portuguese reference center
By Cláudia Varandas, et al
With no recently published studies in Portuguese patients, the authors examined records of people with HAE treated at a single center in Portugal. They concluded that distinguishing between HAE and other common causes of angioedema is vital, leading to reductions in diagnostic delay and improving management, outcomes, and quality of life.
(European Annals of Allergy and Clinical Immunology, September 2024)
Prodromal symptoms of hereditary angioedema (HAE) attacks: A patient survey in UK and Spain
By Patrick FK Yong and Mar Guilarte
The authors indicate that data shows that the majority of HAE patients experience prodromes, where there are signs of an impending attack. However, they feel that research into HAE prodromes is lacking, especially in terms of diagnosis and treatment. Following their research, the authors conclude that patient behavior around early treatment was highly variable, and that better guidance may address this. Additionally, they feel that better understanding of prodromes may help patients better prevent or act earlier to mitigate attacks.
(Allergy, August 2024)
Development and validation of a US quality of life instrument for hereditary angioedema due to C1 inhibitor deficiency
By Anthony J Castaldo, et al
The authors, including Anthony Castaldo and Deborah Corcoran from HAEi and HAEA, developed an HAE-specific quality-of-life instrument that takes account of the unique issues in the US healthcare system. The authors conclude that the new tool, called HAE-C1INH-QoL, is the first HAE-specific quality-of-life tool to be validated in the United States, making it more relevant to US patients with HAE than existing angioedema tools.
(Annals of Allergy, Asthma and Immunology, July 2024)
The CC2D2B is a novel genetic modifier of the clinical phenotype in patients with hereditary angioedema due to C1 inhibitor deficiency
By Nina Rupar, et al
In this genetic-based study, the authors looked for genes related to HAE in families from south eastern Europe. They conclude that their study demonstrated novel genetic factors leading to the variability of C1-INH-HAE. Additionally, they indicate the importance of genes called CC2D2B, CCNJ and ZNF518A.
(Gene, August 2024)
Antisense and CRISPR-based drugs build cases for better hereditary angioedema treatments
By Asher Mullard
With the potential new HAE treatments donidalorsen and NTLA-2002 on the horizon, the authors discuss whether a functional cure could be possible for HAE.
(Nature Reviews Drug Discovery, July 2024)
A human-centered innovative approach based on persona in hereditary angioedema
By Francesca Perego, et al
In this study, the authors investigated whether the process of human-centered design (HCD) could have a role in the care people with HAE receive. They conclude that using an innovative HCD approach based on the person being treated, will extend beyond their physical illness to address psychological and social aspects of the individual’s wellbeing.
(Orphanet Journal of Rare Diseases, August 2024)
Advent of oral medications for the treatment for hereditary angioedema
By Anna Valerieva, et al
The authors look into the possibility of oral treatments for HAE. They conclude that substantial advances have been made in developing oral treatments. They believe that these treatments have the potential to improve and optimize clinical outcomes, satisfaction, and quality of life among patients with HAE.
(Clinical and Translational Allergy, September 2024)
Altered levels of phospholipases C, diacylglycerols, endocannabinoids, and N-acylethanolamines in patients with hereditary angioedema due to FXII mutation
By Anne Lise Ferrara, et al
These authors investigated HAE due to mutations in the FXII gene. They conclude that phospholipase C may have a role as a potential biomarker or therapeutic target.
(Allergy, June 2024)
Validation and correlations of the Angioedema Activity Score (AAS), Angioedema Quality of Life (AE-QoL) questionnaire, and Angioedema Control Test (AECT) in Chinese patients with angioedema
By Hugo WF Mak, et al
The authors aimed to validate HAE-relevant quality-of-life tools in China. They conclude that their study showed that a series of tools are valid and reliable tools for use with Chinese patients.
(Journal of Allergy and Clinical Immunology: Global, July 2024)
Disparities in geography and race in hereditary angioedema: Analysis of 64 trials and 4354 patients
By Hugo WF Mak, et al
The authors indicate a significant disparity in the participation of non-Western and non-White participants in clinical trials for HAE. They believe further global efforts are necessary to improve inclusiveness and deliver more equitable HAE care.
(The Journal of Allergy and Clinical Immunology: In Practice, July 2024)
Early diagnosis of hereditary angioedema in Japan based on a US medical dataset: Algorithm development and validation
By Kouhei Yamashita, et al
The authors introduce their study by showing that, based on prevalence estimates, only 20% of potential HAE cases in Japan have been identified. The authors conclude that using an artificial intelligence model can detect HAE in patients with typical symptoms.
(JMIR Medical Informatics, September 2024)
Analysis of disease burden in patients with hereditary angioedema from Japan by patient-reported outcomes
By Michihiro Hide, et al
In a study conducted before the availability, in Japan, of long term prophylaxis for HAE, the authors aim to provide a benchmark of disease burden on Japanese patients. They concluded that weekly or monthly attack frequencies were associated with high disease burden and that regardless of attack frequency, patients reported fatigue, mood impairment, and depression.
(The Journal of Dermatology, September 2024)
Real-world outcomes of patients with hereditary angioedema with normal C1-inhibitor function and patients with idiopathic angioedema of unknown etiology in Canada
By Adil Adatia, et al
The authors investigated the characteristics and clinical outcomes of Canadian patients with HAE with normal C1-inhibitor. They suggest an unmet need for specific guidelines for these patients, and a better understanding of other underlying disease mechanisms is needed.
(Allergy, Asthma and Clinical Immunology, September 2024)
Long-term prevention of hereditary angioedema attacks with lanadelumab in adolescents
By Timothy Craig, et al
The authors investigated how well tolerated and effective the HAE medicine lanadelumab is in preventing HAE attacks in adolescents with HAE. The authors conclude that lanadelumab provided long-term efficacy in preventing HAE attacks, was associated with clinically meaningful improvements in health-related quality of life and high levels of treatment satisfaction, and was well-tolerated in adolescent patients.
(Annals of Allergy, Asthma and Clinical Immunology, August 2024)
Clinical profile and management of pediatric hereditary angioedema in resource-constrained settings: our experience from a single centre in North India
By Ankur Kumar Jindal, et al
The authors report from a single center in India that treats young patients with HAE. They conclude that this is one of the largest single-centre cohorts of pediatric HAE and the only one from resource-constrained settings. There were significant delays in diagnosis when the age of onset of symptoms was younger, and abdominal attacks were found to be less common in children as compared to adults.
(Immunologic Research, September 2024)
The complexities of decision-making associated with on-demand treatment of hereditary angioedema (HAE) attacks
By Stephen D Betschel, et al
This study aimed to determine patient behavior and the key factors that drive decision-making regarding using on-demand HAE treatment. The authors conclude that the burden of current treatments, such as the need for injections and infusions, may often cause delay, despite patients knowing this may lead to progression of HAE attacks
(Allergy, Asthma and Clinical Immunology, July 2024)
Initial experience of long-term prophylaxis with lanadelumab for hereditary angioedema in China: A clinical observation study on six patients
By Wo Yao, et al
The authors aimed to show the clinical efficacy and safety of using lanadelumab as long-term prophylaxis (LTP) in Chinese patients. These authors conclude that this is the first report of the clinical efficacy of lanadelumab and safety of LTP in HAE patients from the Chinese mainland. They believe the study demonstrates that a ‘reasonable dosage plan’ of lanadelumab can ensure quick and long-lasting protection from HAE attacks.
(International Archives of Allergy and Immunology, October 2024)
Selection of initiatives to improve the management of patients with hereditary angioedema by the hospital pharmacy using the nominal group technique
By José Bruno Montoro Ronsano
The authors aimed to identify and promote a range of initiatives within the hospital pharmacy that could improve the care of patients with HAE in Spain. The initiatives included how medicines are evaluated and selected, how pharmacies dispense medicines, follow-up, telemedicine consultations, patient education, and more joined-up working between other departments. The authors conclude that the implementation of such activities should enhance the way patients with HAE are cared for in Spain.
(European Journal of Hospital Pharmacy, June 2024)
Real-world outcomes in patients with hereditary angioedema prescribed lanadelumab versus other prophylaxis
By John Anderson, et al
Despite the availability of long-term prophylaxis in HAE, there is little real-world data on the use of these preventative treatments, according to the authors. They conclude that their data suggests lower attack frequency, lower symptomatic impact, and better quality of life in patients treated with lanadelumab than other prophylaxis in a real-world setting.
(Allergy and Asthma Proceedings, September 2024)
The Chronic Angioedema Registry (CARE): Rationale, methods and implementation
By Thomas Buttgereit, et al
The authors, including HAEi’s Anthony J. Castaldo and Henrik Balle Boysen, indicate that Chronic Angioedema Registry (CARE) is the first disease registry for recurrent angioedema of all presentations/aetiologies. The authors conclude that CARE will equip physicians with information to enhance patient care and guide future therapeutic decisions in all angioedemas, including HAE.
(Clinical and Experimental Allergy, June 2024)
A real-world study of hereditary angioedema patients due to C1 inhibitor deficiency treated with danazol in the Brazilian Public Health System
By Alessandra Mileni Versuti Ritter, et al
This study aimed to identify and characterize patients with HAE-C1-INH who used danazol prophylactic treatment in the Brazilian Public Health System (SUS) and the healthcare resource utilization (HCRU). The authors conclude that the high rate of attacks, hospitalizations, and general resource use in patients treated with danazol, highlights the necessity to increase awareness of new strategies and accurate approaches to treat HAE patients.
(Frontiers in Medicine, September 2024)
An international survey assessing the effects of the duration of attack-free period on health-related quality of life for patients with hereditary angioedema
By Robbin Itzler, et al
The authors examined whether there was any relationship between the amount of time people live attack-free and their quality of life. The authors conclude that their study showed that the longer patients are attack-free, the better their quality of life. They believe there are opportunities for new treatments to further increase the attack-free duration and improve quality of life for people with HAE.
(Orphanet Journal of Rare Diseases, June 2024)
Deciphering the landscape of hereditary angioedema in India: Perspective for Indian dermatologists
By Prabal Barman, et al
The authors tell us that this paper provides an update on HAE from a dermatologist’s perspective and the availability of first-line treatment options in India. Their conclusions are that:
- HAE must be suspected in a patient presenting with non-itchy/non-urticarial episodic swelling.
- Complement C4 is a simple and sensitive screening test for patients with HAE.
- First-line treatment options for HAE are now available in India and must be used to avoid mortality and improve the quality of life.
- Efforts should be continued to bring better treatment options for HAE.
(Indian Journal of Dermatology, Venereology and Leprology, July 2024)
Real-life experience of subcutaneous plasma derived C1-inhibitor as long-term prophylaxis in HAE-C1NH
By Ana Entrala, et al
The aim of their study was to assess efficacy and changes in health-related quality-of-life (HRQOL) in HAE-C1INH patients treated with SC pdC1INH (Berinert) as LTP under real-world conditions. The authors indicate that the majority of patients saw a reduction in attacks and improvements in their quality of life. The authors also note that using the Spanish Group for the Study of Bradykinin-mediated Angioedema (GEAB) protocol for starting long-term prophylaxis with subcutaneous plasma-derived C1-inhibitor proved useful for individualizing HAE treatment in our case series.
(Journal of Investigational Allergology and Clinical Immunology, July 2024)
Quantification of C1 inhibitor activity using a chromogenic automated assay: analytical and clinical performances
By Yves Renaudineau, et al
The authors found that an automated laboratory test for levels of functional C1 showed good performance, both at the analytical and diagnostic/clinical levels, which allowed its use in a clinical laboratory.
(Clinical Chemistry and Laboratory Medicine, June 2024)
Vascular endothelial growth factor (VEGF) emerging as a mediator of hereditary angioedema (HAE)
By Pedro Giavina-Bianchi, et al
Recognizing the ongoing advancements in our understanding of hereditary angioedema (HAE), the authors advocate for an improved classification system based on an understanding of endotypes, which are the underlying mechanisms of disease. The authors conclude that a precise and dynamic classification system for HAE that evolves with our growing understanding of the disease is needed. They argue that by adopting an endotype-based classification, we can more accurately reflect the underlying pathophysiological mechanisms, facilitating better patient care and more targeted treatments.
(World Allergy Organization Journal, July 2024)
Extension of the circulatory half-life of recombinant ecallantide via albumin fusion without loss of anti-kallikrein activity
By Ghofran Al-Adimi, et al
In this study of a new form of the HAE medicine ecallantide, the authors believed there is potential for the medicine to offer advances over current HAE treatment.
(Journal of Biotechnology, August 2024)
Subcutaneous C1 inhibitor for long-term prophylaxis in hereditary angioedema: A real-life experience
By Krasimira Baynova, et al
The authors report on 22 patients with C1-INH HAE who started subcutaneous C1-INH replacement treatment as long-term prophylaxis during the COVID-19 pandemic. The authors conclude that this treatment option proved to be an effective prophylactic treatment in a series of patients with HAE.
(Journal of Investigational Allergology and Clinical Immunology, June 2024)
Timing of onset of garadacimab for preventing hereditary angioedema attacks
By Petra Staubach, et al
In a letter to the Editor, the authors conclude that treatment with garadacimab results in early and durable protection against HAE attacks from Week 1 sustained to Month 6. The authors believe this contributes substantially towards achieving the primary goal of HAE treatment: complete disease control and normalization of patients’ lives. The authors say that protection against HAE attacks begins after the first administration of garadacimab, allowing clinicians to be confident in its treatment effect as early as Week 1 after treatment initiation.
(Clinical and Experimental Allergy, October 2024)