The ACARE Global Angioedema Forum 2024, affectionately known as the GAF, welcomed 250 healthcare professionals and pharmaceutical industry representatives from across the globe to a two-day celebration of the science behind angioedema and its treatment, with the meeting featuring a particular focus on HAE.

The meeting was the first GAF from the ACARE network, an initiative by GA²LEN and HAE International (HAEi). The GAF ran parallel to the 2024 HAEi Global Leadership Workshop (GLW), and on Saturday afternoon, both meetings joined for a unique opportunity to share knowledge and network.

Due to the breadth of the program for the GAF, Global Perspectives can only hope to give a snapshot of the scientific exchange. We bring you a flavor of GAF.

The GAF in numbers

With 250 attendees and 85 submitted abstracts, the GAF has already attracted some big numbers. However, that’s just the start. Here’s some more of the GAF in numbers:

• 15 chairs
• 28 speakers
• 10 topics talks
• 1 expert panel of 6 doctors
• 4 poster walks and 8 poster walkers
• 3 lunch workshops
• 2 keynote presentations
• 1 interactive patient journey session
• 1 angioedema jeopardy quiz to test clinicians’ knowledge

Opening and introductions

Following the tragic loss of Professor Marcus Maurer, Professor Markus Magerl took on the role of opening the GAF. Fresh from his eulogy to his friend and colleague, Prof. Magerl opened the GAF by welcoming his peers, colleagues, and friends to the meeting.

He noted that the European Accreditation Council for Continuing Medical Education (EACCME) had awarded the GAF 10 European CME credits due to the quality of the agenda, speakers, and scientific content.

Prof. Magerl turned first to the ACARE (Angioedema Centers of Reference and Excellence) network as the driving force behind improved patient care in angioedema, and core to the development of the GAF. He told the audience that the network had reached 103 centers spanning 40 countries, and is now present in all inhabited continents.

Next, Prof. Magerl drew the audience’s attention to the submitted abstracts. He announced that 85 abstracts were submitted. Sixteen were accepted for oral presentation and 73 for poster presentation. He said reviewing such a large body of scientific data is a big job, and Prof. Magerl thanked the entire GAF Steering Committee for their hard work and dedication.

Are you looking for scientific data from GAF?

If you want to read more about the wealth of scientific data presented at the GAF, 80 abstracts are available online.

>> Just click here to access

Prof. Magerl, on behalf of the GAF Scientific Committee, announced that the Young Researcher/Investigator award was given to Dr. Carolina Vera Ayala from the German ACARE at the Institute for Allergology, Charité – Universitätsmedizin Berlin. The Scientific Committee grants the award to an abstract they deem to be of the highest quality and authored by – either solely or as part of a team – a young investigator or researcher. Dr. Vera Ayala’s research was into stopping androgens in patients with HAE: “First Insights from the Global ACARE SHAERPA Study on Androgen Discontinuation in HAE Patients, an Interim Analysis.”

Following the award, Global Perspectives asked Dr. Vera Ayala about her feelings on winning and the GAF in general. She said, ‘It was an incredible honor and a truly surprising and humbling experience. Hearing that my work was recognized with such a prestigious award filled me with immense joy and gratitude. It felt like a validation of the hard work and dedication that went and is still going into the project. I am deeply thankful to everyone who supported me, especially Professor Marcus Maurer, who got me involved in this great project and gave great advice. It is a moment I will cherish and one that motivates me to continue striving for excellence.’

Global Perspectives also asked her about the GAF overall. She said, ‘Attending the first Global Angioedema Forum was an inspiring and enriching experience. It provided a unique opportunity to connect with professionals from diverse countries, exchange ideas, and gain new perspectives. The collaborative environment fostered meaningful discussions on global issues, and it was exciting to see different cultures and expertise come together to address common challenges in managing HAE. Overall, the event was not just about networking but also about learning, innovation, and building relationships that can lead to future collaborations and help improve the lives of our HAE patients.’

‘The GAF provided a unique opportunity to connect with professionals from diverse countries, exchange ideas, and gain new perspectives. Overall, the event was not just about networking but also about learning, innovation, and building relationships that can lead to future collaborations and help improve the lives of our HAE patients.’

– Dr. Carolina Vera Ayala, ACARE Global Angioedema Forum 2024 Young Researcher Award Recipient

First insights from the global ACARE SHAERPA study on androgen discontinuation in hae patients, an interim analysis

Carolina Vera Ayala (Germany)

Dr. Vera Ayala’s abstract was selected as an oral presentation, and she gave it on the first day. She told the audience that the research aimed to determine why, how, and with what consequences androgen treatment is stopped in patients with HAE, and to eventually lead to guidelines on how to discontinue androgen treatment and change to available new medication safely.

The work consisted of research amongst 50 patients in six different centers, and the team intended to extend this to 500 patients.

The key results, presented by Dr. Vera Ayala, were:

• The mean duration of treatment in patients receiving androgens is 116.5 months
• The most commonly used androgen is danazol
• The most common reasons for stopping androgen treatment were side effects and fear of side effects
• There was an almost equal split between physicians who favored tapering the dose of androgens before stopping and those who preferred to stop treatment immediately

Dr. Vera Ayala called upon audience members to consider participating in the forthcoming large-scale global research phase. This data will be used to produce guidelines for patients and physicians on stopping treatment with androgens.

Keynote 1: The Past, Present And Future Of Angioedema

The session Chairs welcomed the first two keynote speakers on stage: Dr. Anjur Jindal from the Postgraduate Institute of Medical Education and Research in Chandigarh, India; and Dr. Henry Li from the Institute for Asthma and Allergy in Maryland, United States.

Dr Jindal spoke first. In a wide-ranging presentation, he covered the following topics:

• Epidemiology of angioedema
• Classification and nomenclature of angioedema (DANCE)
• Disparity in access to diagnostics
• HAE with normal C1 inhibitor
• Biomarkers for angioedema
• Genetics of HAE

Looking at the epidemiology in the Asia-Pacific region, he indicated widespread differences in prevalence, from 0.33 and 1.00 per 100,000 in Singapore and New Zealand, respectively, to as low as 0.02 per 100,000 in India.

On access to diagnostics, he referenced a recent paper that showed that in Asia-Pacific, 71% of centers had facilities to test C1-inhibitor level, and 64% had access to C1-inhibitor function testing. He indicated that variations in access to testing had implications for the diagnostic approach. In some cases, the sensitivity of a C4 test can be increased by drawing blood during an emerging attack, but this does not improve the ability of the test to confirm if a person doesn’t have HAE.

He also noted that HAE with normal C1 inhibitor can only currently be diagnosed by genetic testing.

Looking to the future, Dr. Jindal suggested that there will be:

• More collaborations between clinicians
• Greater understanding of all types of angioedema
• New ways of spotting and differentiating between various types of angioedema and predicting the severity of acute attacks
• A point-of-care diagnostic test for HAE
• Disease-specific patient-reported outcome measures specific to the needs of children and young people
• More equality in access to diagnostic testing, especially in Asia-Pacific

In conclusion, Dr. Jindal told the audience, ‘We need to use our experience in our experiments to achieve our expectations.’

Following on from Dr. Jindal, Dr. Li focused on the treatment aspects. He outlined the marked changes and improvements to the classification and treatment of a wide range of angioedemas.

Looking at the future of HAE therapeutics, Dr. Li highlighted that there are now sixteen existing or forthcoming treatment options that target six separate elements of the system in the body that lead to HAE.

In conclusion, Dr. Li suggested, in common with Dr. Jindal, that there will be an increasing understanding of angioedema, leading to better diagnosis and classification. He was also upbeat about the future of treatment, with improved efficacy, quality of life, and easier administration all on the horizon.

Poster walking

In addition to a full agenda in the main auditorium, the GAF also hosted a packed poster room. While all the posters were deemed important by the Chairs and Scientific Committee, which of the 80 papers should you focus on if you were short of time? Poster Walkers were the answer. These senior clinical leaders curated guided tours of the available data to time-poor attendees.

The poster walkers selected one poster per walk as the highlight of their walk. We offer our congratulations to the following presenters:

• Impact of Hereditary Angioedema Attacks on Quality of Life and Ability to Work Among UK Patients Receiving Long-term Prophylaxis or On-demand Treatment Only. Patrick Yong, United Kingdom
• Self-Reported Treatment Preferences of Patients Switching from Prior Prophylactic Therapies to Donidalorsen for the Treatment of Hereditary Angioedema: Results from the Phase 3 OASISplus Study. Danny M. Cohn, Netherlands
• Predicting Hereditary Angioedema Prognosis with a Next-Generation Sequencing Angioedema Panel. Joseph Chiao, USA
• Prevalence of Autoimmune Diseases in Iranian Patients with Hereditary Angioedema. Mohammad Reza Fazlollahi, Iran

Here, Global Perspectives catches up with three of the GAF Poster Walkers to get their views on some of the key aspects of angioedema science that caught their eye.

Dr. Philip Li, University of Hong Kong, Hong Kong
What, if any, were the key themes from the posters you chose for your walk?
There was a wide and good variety of posters on our walk. The themes were mainly on improving diagnosis and novel strategies for HAE management.

Why did you choose the posters you chose?
Based on novelty and equity to give representation from all regions, not just Western or industry-sponsored abstracts.

What did you think of the quality and breadth of posters?
Overall, very good and extremely broad, from developments in middle/lower income countries through to ground-breaking and cutting-edge technologies from developed regions.

What would you want patients to know?
GAF is a showcase demonstrating the global effort and collaboration (East and West) to tackle HAE together.

What does the future of research in angioedema and HAE look like to you?
We are no longer counting attacks or measuring symptoms; we are looking at quality of life – and, more importantly, normalization of quality of life. With that – we are looking closer and closer to a cure!

Dr. Mark Scarupa, Institute for Asthma and Allergy, Maryland, United States
What, if any, were the key themes from the posters you chose for your walk?
I don’t think there was a specific theme. I was impressed by the diversity. There was translational research, multicenter clinical trial data, epidemiology, and posters on the impact of patient advocacy. This diversity was in the posters we selected and throughout the poster session.

Why did you choose the posters you chose?
I was most interested in a mix of trial results, as those posters speak to where HAE therapies are heading and epidemiology.

What did you think of the quality and breadth of posters?
Very high. Whether it was posters organized by HAE societies and patient-centered groups or scientists, they were well thought out and informative.

What would you want patients to know?
Patients should know the breadth of international interest and expertise in HAE. There are great minds and enthusiastic patient advocates present on all continents.

What does the future of research in angioedema and HAE look like to you?
Historically, we have focused on attack rate reduction, speed to symptom resolution, and mechanism of action. As therapies continue to evolve, there is increasing focus on patient quality of life and a hope that patients, over time, can view their disease as completely manageable.

Professor Konrad Bork, University Medical Center, Mainz, Germany
What, if any, were the key themes from the posters you chose for your walk?
Together with Dr. Luis Felipe Ensina from Brazil, we reviewed the abstracts of 16 posters, which covered various topics around hereditary and acquired angioedema.

Why did you choose the posters you chose?
Dr. Ensina and I selected five especially outstanding posters based on excellence in content and presentation, and all posters led to a lively discussion.

What did you think of the quality and breadth of posters?
All posters were of high quality and were interesting for physicians, patients, and generally all people dealing with hereditary and acquired angioedema. Finally, according to the criteria mentioned, we chose one poster as the highlight.

Keynote 2: The emerging spectrum of hereditary angioedema and the algorithmic diagnostic workup

On the second day’s morning, delegates heard the second keynote lecture, this time on diagnosing the spectrum of HAE. The speakers here were Dr. Laurence Bouillet from the French National Reference Center for Angioedema at the Grenoble University Hospital, France; and Dr. Avner Reshef from the Angioedema Research Center at Barziliai University Medical Center, Israel.

Speaking first, Dr. Bouillet concentrated on an algorithm-based diagnostic process for isolated angioedema. The plan focused on five aspects of diagnostic decision-making:

• Definition of isolated recurrent angioedema
• Drugs and angioedema
• Family history of angioedema
• Biological analyses
• Response to therapy

Dr. Bouillet discussed aspects to consider with recurrent angioedema, such as the sudden onset and long duration of symptoms, and that it resolves without damage to the body. The absence of hives is also important, as are reactions to drugs such as ACE inhibitors or some painkillers (NSAIDs).

Dr. Bouillet also discussed the importance of family history in diagnosis. However, she cautioned clinicians to consider that 25% of mutations are de novo, meaning there is no family history, and that in 15% of people with a mutation leading to C1-inhibitor deficiency, there are no symptoms.

Dr. Bouillet was clear that with any type of bradykinin-mediated angioedema, only a test of C1-inhibitor levels can rule out HAE due to C1-inhibitor deficiency.

In conclusion, Dr. Bouillet outlined five key considerations:

• Rule out drug-induced angioedema
• Check out the family context with caution
• Check out C1-inhibitor function and propose genetic tests
• Assess the response to long-term prophylaxis treatment (anti-H1 and omalizumab)
• Think about trigger factors and abdominal attacks

Closing this keynote was Dr. Avner Reshef. He focused on the emerging spectrum of angioedema and its classification.

Starting with the system of classification whereby angioedema was defined according to whether it was histamine-mediated or bradykinin-mediated, Dr. Reshef then indicated that around ten years ago, this moved on to a focus on known biomarkers and genetic mutations at the time.

Fast forwarding to 2024, Dr. Reshef showcased DANCE, a new global consensus on how angioedema is defined and classified. He indicated the six key principles of DANCE:

• A comprehensive classification covering all angioedema syndromes due to vascular-endothelium hyperpermeability
• Integration of phenotypes, pathomechanisms, and genomics (types, endotypes)
• Re-classification of ‘normal C1-INH’ genetic variants
• Clear terms and consistent wording of acronyms/abbreviations
• Agreed and consented by an international panel of angioedema experts
• Assimilation of this new vocabulary into future scientific publications

Turning his attention to the genetic work-up of HAE with normal C1 inhibitor (HAE-nC1INH), Dr. Reshef highlighted the following key considerations:

• Patients who are suspected to have HAE-nC1INH should be assessed for known mutations underlying HAE-nC1INH
• Variable family history and lack of specific biomarkers hamper the correct diagnosis and management of HAE-nC1INH patients
• Genetic evaluation is an imperative unmet need for angioedema patients without a definitive diagnosis
• Genetic testing is required to establish the diagnosis

Dr. Reshef concluded by referencing that the DANCE work was published just days after the disappearance of Prof. Marcus Maurer and that he would continue to work with others to fulfill Prof. Maurer’s legacy.

Lunch workshops: The unknown variant and what to do next

During the lunch break of the GLW, Global Perspectives jumped into the GAF to bring readers a flavor of one of the 3 GAF lunch workshops: What to do when genetic testing shows an unknown variant? Hopefully, it will dispel some of the complexity around how and when genetic testing is used, and give patients more understanding of the challenges facing doctors trying to diagnose extremely rare forms of HAE.

Professor Anastasios Gemenis from the University of Thessaly in Greece and Dr. Anna Valerieva from the University of Sofia in Bulgaria, led the workshop.

Dr. Valerieva explained that the workshop aimed to help clinical colleagues understand what to do when there is difficulty in interpreting genetic test results and the mutations identified. Firstly, she reminded the audience most HAE is associated with a deficiency of the C1 inhibitor protein. For these people, there is ordinarily no need for genetic testing to diagnose. Complement tests that assess the function of the C1 inhibitor protein and C4 protein level are commonly used and confirm most cases of HAE due to C1 inhibitor deficiency. There are some cases when genetic testing may be used, such as when complement testing is inconclusive or in newborns whose complement system is not mature.

Understanding the genetic mutation is important for diagnosis and treatment in the much less frequent cases of HAE where patients have normal C1 inhibitor values. You can learn more about this in Prof. Marc Riedl’s GLW presentation, ‘The latest on HAE with normal C1-inhibitor’.

Dr. Valerieva indicated that eight mutations have been identified as leading to HAE with normal C1. However, this doesn’t account for all cases. The majority are still classified as unknown HAE.

Dr. Valerieva helped explain some of the jargon surrounding genetic mutations:

• De Novo mutations are those found for the first time in a family or a patient but have previously been seen in other patients.
• Novel mutations are those which have never been reported in any patient.

The clinicians then went on to discuss two cases. The first was a boy with HAE with C1 inhibitor deficiency. Would his younger sibling (a sister) be at risk of HAE?

Genetic testing demonstrated a novel variant, a new mutation never seen before. However, Dr. Valerieva said it was not straightforward to interpret whether this causes disease. There is no previous data on such completely new mutations. Looking at family history can help, and bioinformatics can use computer power to analyze whether a gene or the resulting protein is likely to cause disease.

Dr Valerieva said the resulting information should always be shared with the scientific community, as it will create a database that doctors can search to diagnose or give peace of mind to families.

Through extensive genetic detective work, they determined the girl did not have HAE.

The second case was related to a man suspected of having ACE inhibitor-related angioedema, but despite stopping these medicines over a year ago, he continued to have attacks.

The assembled clinicians discussed medical treatment for the patient, as specific therapies act to diagnose the form of angioedema when effective. In this case, this course of action did not help. Ultimately, the treating clinicians needed not to discount HAE with normal C1. The resulting genetic testing indicated that they were right; the patient suffered from HAE associated with a plasminogen mutation.

Dr. Valerieva concluded that family counseling can be challenging in patients with HAE with normal C1, as the mutation is only sometimes passed on to other generations.

A spot of Angioedema Jeopardy

While many patients and caregivers will be aware of their form of angioedema jeopardy relating to diagnosis, treatment, attacks, and quality of life, we invited clinicians to use the Angioedema Jeopardy section of the GAF. This session pits clinicians’ knowledge and skills against their peers in a series of questions with varying difficulty.

Led by Professor Marc Riedl, who took the quizmaster role with aplomb, the audience split into two groups. Each audience member had a red card (representing false) and a green card (representing true). Replicating the Jeopardy TV gameshow board, Prof. Riedl offered each group a series of categories and points. Once selected, the audience was shown a statement, to which each member of the playing group showed their red or green card. The resulting average answer decided if the group was correct and took the points. If yes, the group selected another category and points; if not, the play moved to the other side of the audience.

The expert panel on-stage offered their feedback on answers. Some questions caused a lot of discussion! One question that stumped much of the audience was about the make-up and role of ACARE. Less than half understood that the ACARE network is a partnership between GA²LEN and HAEi, compared to, e.g., UCARE, which is only a GA²LEN initiative.

Eventually, at the end of a hard-fought game, one side of the audience won by only 10 points! One lucky winning team member even went home with an ACARE hoodie as a prize.

The immediate feedback from the meeting was excellent and will be collated and shared in future Global Perspectives. Speaking on behalf of the entire GAF organizing team, Debs Corcoran, HAEi’s Chief Scientific Officer, said, ‘We’re delighted with how wonderfully this first GAF was received and the knowledge and energy participants are taking home. Thank you to everyone who made the meeting a success!’