Disclaimer: This podcast miniseries is supported by a grant from Takeda.

Dr. Kristin Sokol (Host): Despite its rarity, hereditary angioedema, or HAE, has a profound impact on the lives of many patients. As healthcare providers, the ability to recognize and diagnose HAE early, especially in pediatric patients, can make all the difference in improving patient outcomes and quality of life.

However, the challenges of diagnosing HAE, particularly in minority and rural populations, remain significant. The goal of this podcast miniseries, Pediatric Hereditary Angioedema, also known as HAE, Diagnosis and Management, Challenges, Barriers, Strategies, is to explore how we can overcome barriers from early recognition in childhood to managing long-term care and understanding the genetic and acquired forms of this disease. We'll also discuss the crucial role you play in identifying this condition before it's too late. Hello, everyone.

My name is Dr. Kristin Sokol, and I will be your host for this three-part mini-series entitled Pediatric Hereditary Angioedema Diagnosis and Management: Challenges, barriers, Strategies. I'm a board-certified allergist-immunologist and board-certified pediatrician practicing at Schreiber Allergy in the D.C. Area and currently serving as the Chair of the ACAAI Annual Program Committee.

In this episode, the third and final in our miniseries, we will discuss long-term management strategies of HAE, when to start prophylaxis, and how to help pediatric patients with HAE transition into adulthood. I'm excited to be joined by two HAE experts. Our first expert is Dr. Aleena Banerji. Dr. Banerji is a professor at Harvard Medical School and Clinical Director of the Allergy and Clinical Immunology Unit at Massachusetts General Hospital in Boston, Massachusetts. Dr. Banerji has collaborated with industry on multiple clinical trials, evaluating novel agents for hereditary angioedema, and has published over 50 peer-reviewed manuscripts, including national and international guidelines for the management of hereditary angioedema. She also serves on the medical advisory board for the U.S. Hereditary Angioedema Association. Dr. Banerji, welcome back to the show.

Dr. Aleena Banerji: Thanks for having me, Kristin.

Host: Our second expert is Dr. Jonathan Bernstein. Dr. Bernstein is a Professor of Medicine at the University of Cincinnati College of Medicine, Department of Internal Medicine in the Division of Rheumatology, Allergy, and Immunology, and partner of Bernstein Allergy Group and Bernstein Clinical Research Center in Cincinnati, Ohio. He is the immediate past president of the Quad AI and also serves on the medical advisory board for the U.S. Hereditary Angioedema Association. Dr. Bernstein, thanks for coming back to the show.

Dr. Jonathan Bernstein: Thanks for having me, Kristin.

Host: All right. Well, let's get started with our third episode. Aleena, let's begin with you. It seems like many or most patients will benefit from long-term therapy to prevent HAE attacks. Is long-term prophylaxis needed for every patient with HAE? And how do you personally choose which agent is prescribed for your patients?

Dr. Aleena Banerji: Thanks, Kristin. I think this is a really important question for anyone that's managing a patient with hereditary angioedema. You know, we certainly know that long-term prophylaxis can significantly improve the quality of life for many of our patients with hereditary angioedema, but it's not necessarily the right answer for everyone. It's really a joint decision made together with the patient and includes a discussion on many factors. These factors can include the severity and frequency of their HAE attacks, their quality of life, are they tolerating the treatment? Is it working for them? Are there side effects? What is the cost to the patient? And what is their access to emergency or on-demand treatment? How easy is it, if they were having a life-threatening attack or an abdominal attack to seek urgent care? And really, ultimately, the decision to initiate or even to continue long-term prophylaxis with the patient is individualized. And we really do have to think through all of these factors and engage in shared decision-making with that patient and make a plan. And that plan is an ongoing conversation and not just necessarily today's decision, and to continue followup and continue to have ongoing conversations with that patient over time.

Host: Thank you so much, Aleena. Yeah, as someone who takes care of pediatric HAE patients too, I find it so important to just form long-term relationships with them. And the shared decision-making comes into play for every decision we make for these patients. So as previously mentioned in our episodes, there are several options for long-term prophylaxis. So Jonathan, what do you discuss with your patients when determining what is the best fit for them?

Dr. Jonathan Bernstein: So as Aleena stated, I'd like to try to provide options to patients and to make sure that they're well-educated about all of the available treatments. And so, my motto is an educated patient is a good patient. And so, again, you share decision-making to really review these treatments. And we talk about whether or not all they need is on-demand therapy. If they're having more frequent attacks, of course, they would be candidates for long-term prophylaxis. But if they're having even intermittent abdominal attacks that aren't that frequent, but are very debilitating, they could still be a candidate for long-term prophylaxis. And of course, if they have a history of throat swelling, you know, even if it only happens once or twice, that could still be an indication depending on patient's preferences and values.

So, we go through the routes of administration, we talk about side effects, and the efficacy in clinical trials and that usually helps patients make decisions. They like our input though. They want us to know what our experience has been with other patients. And when you're talking about children, this is a little more delicate because children don't like needles. This is a new frontier for them, a new experience. So, we really have to take that into consideration. Of course, lanadelumab is approved down to two years of age. One can also give IV C1 inhibitor, plasma-derived C1 inhibitor, and one can also provide subcutaneous C1 esterase inhibitor. The C1 inhibitor has to be administered subcutaneously more frequent. So, this could be a deterrence for some children who don't want to have to get a needle every three to four days versus lanadelumab, which can be given every two weeks initially. And if they have no attacks over six months, then they can go out to once a month. So, ideally in the future, we'll have oral therapies and that are available down to these young age ranges. Right now, they're not approved. We do have one oral prophylactic therapy, but I think it's only down to 12 years of age presently. And we don't have anything for the younger children. But hopefully in the future, we'll have more therapies and that'll make it easier to select treatment that would be more palatable for these very young children who do need prophylactic therapy. But I think at the end, it's not always what you think it is. It's not one-size fits all for these patients. And I'm always surprised how patients think about treatment and what therapy they actually prefer and what they actually select. It's not always intuitive or obvious.

Host: That's right, Jonathan. It's definitely not a one-size-fits-all approach. Thank you so much for that. Aleena, so in addition to long-term prophylaxis, there's also options for short-term prophylaxis in acute situations. Can you tell me a little bit more about these short-term prophylaxis options and how you decide which is best for your patients?

Dr. Aleena Banerji: We often focus on on-demand and long-term prophylaxis as really the two big buckets. But short-term prophylaxis is really an important third bucket in the management of patients with hereditary angioedema. And really, short-term prophylaxis is when the child or the patient with hereditary angioedema is facing a potential known trigger that could lead to an attack. So for example, is it dental cleaning or a dental visit for that child? Or is there an upcoming surgery or procedure that would trigger symptoms?

And so, the good news is we do have effective options for short-term prophylaxis to prevent attacks in these situations. And that includes using a dose of C1 inhibitor replacement before a procedure. Also, androgens such as danazol for five days prior to that trigger or procedure is certainly a reasonable option. We don't necessarily like to use androgens in the pediatric population, but a short course of five days, maybe not as concerning in terms of side effects. And if you don't have access to C1 inhibitor, the androgens or danazol for five days is another option.

For major surgeries or procedures that really are at high risk of triggering an attack, I think short-term prophylaxis is very important. In contrast to maybe dental cleaning and specifically in an individual that's already on long-term prophylaxis, I think it's a mutual shared decision with that patient or that child's parents to really think about whether we want to use short-term prophylaxis or not and make a decision together.

Host: Great. Thank you so much, Aleena. So, it sounds like there's lots of decisions to be made for a patient, a pediatric patient with this condition. And lots of decisions are probably made by the parents and the provider when the child is young, but we obviously have to manage these pediatric HAE patients through adolescence and into adulthood, and this can be challenging with any chronic condition. So Jonathan, can you tell us how you approach the transition for patients with HAE?

Dr. Jonathan Bernstein: Well, this is a very challenging, issue, whether we're treating with HAE or any chronic condition like asthma or other conditions where the patient really has to be responsible for their care. So, we really have frank discussions with the patients and their caregiver and really try to emphasize the importance of them being involved and responsible for their care and treatment. And many adolescent patients, you know, as they get older, they don't bleed, they're invincible. And so, they have to understand The seriousness of this disease.

They're also doing things that are potentially going to lead to an episode. They're doing playing contact sports, which they want to continue to do, it's something they enjoy. But as you know, physical trauma can sometimes be a trigger for a swelling episodes, not always, but it certainly can be. So, this is motivating for them to be more responsible and vigilant with being adherent to their medications. But it's really important that as we see these patients, we see them periodically not just once every couple of years, but at least once a couple times a year to reinforce these important concepts and make sure they're actively participating in their care and they're part of the conversation, not just their caregiver in using these shared decision principles.

Host: Thank you so much, Jonathan. It's really important to identify as we care for these patients with HAE. So thank you, Jonathan, thank you, Aleena, our experts for sharing your valuable insights today. It's clear that there are options for treatment, both long-term and acute in our patients with this chronic condition. So, we hope this discussion has offered our listeners practical guidance on selecting appropriate management strategies for your HAE patients and supporting their transition into adulthood.

So, this concludes part three of our three-part miniseries, Pediatric Hereditary Angioedema Diagnosis and Management, Challenges, Barriers, Strategies from the ACAAI. You won't want to miss parts one or two. So, please be sure to go back and listen to those episodes if you haven't already. And for other interesting podcast episodes and to claim CME for this episode, please visit education.acaai.org/allergytalk. I'm Kristin Sokol for the American College of Allergy, Asthma, and Immunology. Thank you to our listeners and to our esteemed guests. I hope everyone has a great day.