This article is part of an extensive feature on the 2024 HAEi Regional Conference Americas, published in Global Perspectives #1 2024
Scientific Session, Saturday
Running concurrently with the Patient Track, the Scientific Track of the 2024 HAEi Regional Conference Americas was the hub for the latest data and discussion on the diagnosis and treatment of HAE. Three physicians from across the Americas region chaired the Scientific Track: Prof. Anete Grumach from Brazil, Dr. Olga Barrera from Panama, and Prof. Marc Riedl from the USA, and welcomed 75 attendees to the program.
The assembled physicians had a full program of presentations and discussions on Saturday morning. The Co-Chairs presented the Young Researcher/Investigator award to Dr. Karla Robles-Velasco from Ecuador. You can read about her award-winning research in the oral abstract presentations.
Invited Talk: Obtaining Medication for HAE in our Central American Region
Dr. Francisco Alberto Contreras-Verduzco, Mexico, told the assembled delegates that he would provide an update on the situation in the Central American region. He categorized the region as having little territory and a large population but little development, noting that only 2 countries have adequate scores according to the Human Development Index. As a result, he highlighted four main challenges to access for HAE medicines:
- Limited availability
- High costs
- Lack of awareness
- Underdeveloped health infrastructure
To learn more, Dr. Contreras-Verduzco contacted the health ministries in all 7 Central American countries: Belize, Costa Rica, El Salvador, Honduras, Guatemala, Nicaragua, and Panama. Unfortunately, he received mixed responses; some great, some a little or nothing. Speaking with colleagues in these countries, he showed that there are more than 137 patients diagnosed across the region, but prevalence data indicates that there are likely to be more than 1000 patients with HAE in the region.
On available medication, Costa Rica approved icatibant and plasma-derived C1-inhibitor in 2023. Beyond this, no other countries have approved medications recommended as first-line HAE treatment. Where possible, wealthier patients can travel abroad, commonly to Colombia and Mexico, to acquire medicine. Some patients are also able to access donated medicine. He cautioned that most patients do not have the money to obtain treatment for the rest of their lives. Without a regular supply of HAE medicine to the countries in the region, there are growing concerns that people are obtaining medicine, potentially fake, from alternative channels.
Dr. Contreras-Verduzco proposed 8 areas in which patients could be better supported to access HAE medicines:
- Education and awareness – to reduce stigma and lead to earlier diagnosis
- Health policy development – to promote the participation of HAE patients in the development of appropriate health policies
- Specialized clinics or reference centers – to create centers of excellence to act as reference centers for other hospitals and to support diagnosis and treatment
- Training of health professionals – to address a lack of knowledge about rare diseases
- Data collection and patient registry – to understand the needs and prevalence of HAE in the region
- Support for patient groups – to work together to improve the quality of life for patients
- International collaboration – to partner across borders to improve research and development
- Access to treatment – To enact medication access programs, negotiate prices, and import generics as appropriate
Dr. Contreras-Verduzco concluded that a patient registry is imperative to understand the situation better. Through collaboration with governments, healthcare professionals, patients, and other stakeholders, it is possible to address the complex challenges of improving access to medicines for rare diseases like HAE.
Invited Talk: Diagnostic approaches to the different types of HAE
Global Perspectives caught up with Dr. Ricardo Dario Zwiener, Argentina, ahead of his talk. We asked him to tell us a little about the talk he will give.
“The diagnostic approaches to different types of HAE are very important. It helps us give an early and accurate diagnosis of HAE, which is critical for patients and their families or caregivers.”
“I always say that HAE is like a wolf in sheep’s clothing because it can be confused with many allergic conditions. Without a diagnosis, a patient is always at risk of death because HAE is a life-threatening condition.”
“As physicians, we have different tools to diagnose HAE. The first is taking a patient history. When we talk to the patient, we get their viewpoints and hear about things like recurrent episodes of unpredictable edema with wheals, recurrent abdominal pain, and perhaps even an affected relative. The lack of response to classical anti-allergic treatment like corticosteroids and antihistamines and increased attacks after things like oral contraception are all important clues.”
“If, after the patient history, we suspect that the patient could have HAE, we ask for a lab to confirm our clinical suspicion. If that is normal but the suspicion remains high, we can seek genetic tests to search for another mutation. I am from Argentina, and in my country, we have a center to analyze blood samples and perform genetic testing. We also offer genetic counseling, especially to others in the family who may have the disease.”
How could patients and caregivers help in the diagnostic process?
“Asking HAE patient associations for a physician recommendation can help get someone with the right experience. Establishing a good relationship between physician and patient is essential. Both should be able to work together as a team to get a plan of action.”
What do you think still needs to improve in terms of diagnosis?
“Awareness is the first issue. It is a global problem. We all need to join forces: patients, caregivers, physicians, advocacy organizations, and the pharmaceutical industry to improve diagnosis, testing, and access to medication.”
“I think a patient has a right to have an accurate diagnosis. A correct diagnosis is the key to understanding this isn’t psychological, and it means access to medication. You are more protected.”
Thank you. This is clearly an important topic for you.
“Everyone has a purpose in life. One of my main purposes is to help HAE patients survive, reach an early diagnosis, and have medications to control the disease. I work with HAE Argentina, the patients’ association. Together, we help patients and caregivers with medication, support, and education. For me, HAE patients really are heroes.”
After the oral presentations, the Scientific Track heard clinical case presentations from the Co-Chairs. This was followed by a discussion of these cases among the attending delegates.
Prof. Marc Riedl presented the case of a 23-year-old female with HAE type I, treated with lanadelumab and stable for four years. At a more recent follow-up, the patient said that abdominal symptoms had led to around 15 days off work in the last six months and that icatibant only seemed to help on occasion.
Prof. Riedl asked delegates what else they would like to know to better respond to the patient, before describing a series of diagnostic tests that showed mild anemia, some enlarged lymph nodes, and a little thickening of the wall of the intestines. The patient was referred to a gastroenterology expert who -ultimately- diagnosed chronic gastritis and celiac disease. The patient’s symptoms improved with medication and dietary changes.
He counseled delegates to consider the following when distinguishing an HAE abdominal attack from other causes of abdominal pain:
- Most abdominal HAE attacks are not associated with fever, peritoneal signs, or raised white blood cell count
- Elevated blood values (such as raised neutrophil counts, hypovolemia from fluid loss, and hemoconcentration) are reported in severe attacks
- Imaging is not routinely necessary in a known HAE patient with characteristic symptoms
- Bowel wall swelling may be found later in an attack
Finally, he clarified that a clear response (or lack of response) to effective on-demand medication should be a sign that it may not be an HAE attack. C1-INH level or function can be a useful biomarker while on C1-INH replacement therapy.
Prof. Grumach presented her case of a 21-year-old patient hospitalized 5 times in 10 years due to lip swelling and abdominal pain. Prof. Grumach saw the patient for the first time in 2021 and worked systematically to establish a diagnosis. She advised that the patient was previously non-responsive to antihistamines and steroids before asking the audience what percentage of angioedema patients do not respond to antihistamines (answer: 15-20%).
The association of subcutaneous and abdominal symptoms and self-limiting and recurrent attacks helped guide a diagnosis of HAE. However, the woman was the only one in her family affected, had late onset of symptoms and normal C4 and C1-INH values. This led to a suspicion of HAE with normal C1 inhibitor. The audience was asked if they would conduct genetic testing (100% yes). Prof. Grumach confirmed that genetic testing had occurred, and the patient had a mutation of Factor XII.
Prof. Grumach concluded by telling the audience that angioedema must be evaluated as a symptom associated with several factors. She reminded delegates that mast cell-mediated angioedema is the most common type of angioedema and that there is, as yet, no ideal biomarker for recurrent angioedema.
During the Scientific Track, 5 oral abstract presentations were given, allowing participants to hear new scientific data on HAE and its treatment.
Relationship Between Time to On-demand Treatment and Quality of Life During Hereditary Angioedema Attacks
Global Perspectives spoke to Prof. Sandra Christiansen. We asked her to summarize the key implications of the research she was presenting. She said:
“This is part of a cooperative effort with HAEA in the United States. We focused on the use of on-demand therapy in people with HAE (C1-INH); what are people doing and why? We recruited 94 individuals, including some adolescents over the age of 12, divided between people who only had on-demand therapy and those with on-demand plus long-term prophylaxis.”
“We’re all aware that the guidelines indicate that all attacks are worthy of treatment to reduce morbidity and prevent mortality. And, that you should treat as soon as you recognize you’re having an attack. That’s the message that we think we’re conveying to patients.”
“In the study, the average delay to treatment was close to four hours, ranging from one hour or less to over eight hours. There also appeared to be a connection between the delay in on-demand medication usage and quality of life.”
“The bottom line is that people with HAE wait too long before they treat an attack. The longer we wait, the worse the consequences. As doctors, we need to do better in our message to patients: treat early and treat all. And we have an unmet need, particularly for adolescents, who in the United States only have intravenous options.”
Efficacy and Safety of Bradykinin B2 Receptor Antagonism with Oral Deucritibant in Prophylaxis of Hereditary Angioedema Attacks: Results of CHAPTER-1 Phase-2 Trial
Global Perspectives asked Prof. Marc Riedl to summarize the implications of his research. He told us:
“This presentation is on a medicine that’s actually being studied for treating attacks on-demand, and also for preventing attacks. I’m sharing some data on the preventative approach. This is a targeted oral medicine, taken on a long-term basis, designed to prevent attacks. In this phase-2 trial, we compared it to placebo and saw that it looked effective and safe. A longer, larger, phase-3 study needs to be conducted to prove that it’s both safe and effective.”
“We continue to look for additional effective, potentially less burdensome ways to prevent attacks and this may be one strategy to do that. Oral medicine may be easier to administer, which may be useful in getting access to medicines in places currently experiencing challenges. It’s another potential step forward in the quest to really bring more effective, safer, and potentially less burdensome treatments to more people with HAE.”
Long-Term Effectiveness and Safety of Lanadelumab Treatment for Hereditary Angioedema in Patients from Puerto Rico: Data from the EMPOWER Study
Dr. Rafael Zaragoza-Urdaz told the audience that the EMPOWER study was designed to evaluate the long-term effectiveness and safety of lanadelumab in the United States and Canada. He presented data on Puerto Rican HAE patients who were treated with lanadelumab for up to three years.
Dr. Zaragoza-Urdaz gave a breakdown of the clinical trial methodology and details on the patients. He showed that pre-enrollment, ‘new user’ study participants from Puerto Rico had 2.22 attacks per month, reducing to 0.91 per month over time. In the larger group of ‘prevalent users’ (patients who had received 4 or more doses of lanadelumab at enrollment), the attack rate per month was 0.36. There were few reported side effects caused by treatment.
In conclusion, Dr. Zaragoza-Urdaz said that the EMPOWER data from Puerto Rico show reduced HAE attack rates after patients start on lanadelumab, and this low attack rate was maintained for up to three years. He described the treatment-related adverse events as non-serious and that lanadelumab was well tolerated overall.
Screening Sleep Disorders in Hereditary Angioedema: A Comprehensive Cross-sectional Study
Global Perspectives asked Dr. Karla Robles-Velasco to tell us about her award-winning research.
“In the general population, a sleep disorder can lead to many adverse health outcomes, like cardiovascular diseases. HAE patients already have a chronic inflammatory disease that involves many immunologic pathways and has a high impact on their lives. We believe it is important to identify and treat sleep disturbances in HAE to avoid adverse health outcomes in the future.”
“We found that more than half of our participants had at least one sleep disturbance, with the most common being insomnia. More than 30% of our patients also had a risk of obstructive sleep apnea.”
“Patients who have a sleep disturbance have worse HAE activity and worse quality of life. Patients should talk to their doctor if they don’t have control of their disease, if they are not responding to treatment, or if they have higher disease activity. It could be an underlying sleep disturbance that is having an impact on their HAE.”
Understanding Patient Reasons not to Treat All Hereditary Angioedema (HAE) Attacks and Characteristics of Untreated HAE attacks: Results from a Real-world Survey
Global Perspectives asked Prof. William Lumry to tell us more about his research. He told us:
“This was a real-world survey based on physician-diagnosed HAE patients. Around 60% were on long-term prophylaxis, and only 75% reported being prescribed on-demand treatment, which is somewhat against the guidelines. We recommend that everybody have an on-demand therapy available, whether they’re on prophylaxis or not.”
“We asked patients; did you treat your most recent attack? 85% said yes. When asked how long it took from the time they had symptoms to the time they treated. The median time for how long it took from the start of symptoms to the time they treated, was immediate. The duration of an untreated attack is in line with what we would expect, around 15 to 20 hours of symptoms.”
“A little bit distressing is that 15% of patients who chose not to treat had to go to the emergency room or be admitted to the hospital because of the HAE attack. Half said they didn’t treat the attack because it didn’t proceed. In some cases, patients reported forgetting to take their medication or being concerned about the time and inconvenience of starting an IV or having an injection. The key message for patients is to follow the guidelines and treat attacks early. Period. Don’t wait. Even an attack that starts out mild may turn into something that takes you to the hospital.”
Find more feature articles from the 2024 HAEi Regional Conference Americas:
