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Hereditary Angioedema
96 Plays1 year ago
Dr. Susan Waserman speaks with Dr. Dawn Goodyear and Dr. Adil Adatia about the treatment and management of hereditary angioedema.
This episode of Science for the Real World is part of Canadian Allergy & Immunology Today, an open access scientific journal for the allergy & immunology community.
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Transcript
Introduction to Hereditary Angioedema Episode
00:00:03
Speaker
Welcome to Science for the Real World, conversations with Canadian clinicians. This episode, part of Canadian Allergy and Immunology Today, is about the treatment and management of hereditary angioedema and is sponsored by BioChrist.
Meet the Experts: Dr. Goodyear and Dr. Adatia
00:00:17
Speaker
Our moderator, Dr. Susan Wasserman, is joined by Dr. Don Goodyear and Dr. Adil Adatia.
00:00:26
Speaker
Hi, everyone. My name is Susan Wasserman. I'm an allergist immunologist at McMaster University, and I'm delighted to be joined by two of my colleagues, Dr. Dawn Goodyear, a hematologist from Foothills Hospital in the University of Calgary, and Dr. Adil Adatya, an allergist immunologist from the University of Alberta. And tonight we're going to talk about the treatment and management of hereditary angioedema. So let's start with you, Dawn, if that's
Understanding Hereditary Angioedema: Symptoms and Challenges
00:00:56
Speaker
okay.
00:00:56
Speaker
Orient us to hereditary angioedema. How are patients generally presenting to you and what are the symptoms that you typically see? Thank you, Susan. It's my pleasure to be here. Hereditary angioedema is a fascinating rare inherited condition that is associated with recurrent episodes of angioedema or swelling.
00:01:19
Speaker
which we typically refer to as HAE attacks. It has a number of interesting unique characteristics that lead to challenges for both treaters as well as patients and caregivers. The symptoms of HAE are primarily due to temporary leakage of plasma from blood vessels into surrounding tissues, and that's what leads to the clinical manifestations.
00:01:41
Speaker
HAE is characterized by unpredictable, painful swelling that can affect any location, but common sites include the extremities, abdomen, genitals, and face. And one of the difficulties is that the severity of symptoms can vary from very mild to debilitating or even disfiguring.
00:01:59
Speaker
And patients often find and report that the symptoms can even vary between attacks. The agent onset of symptoms can vary, although it typically occurs around the time of puberty. But there is often a delay in recognition of the diagnosis. In the literature, it indicates anywhere from eight to 12 years. So during that time, patients may be exposed to ineffective treatments. They may undergo unnecessary procedures and have negative experiences with the healthcare system.
00:02:25
Speaker
But certainly the most feared complication of HAE is angioedema involving the throat or oropharynx, which can result in airway obstruction. Thank you for that excellent overview of a real myriad of symptoms that you're seeing. And I was just going to ask you in addition, do you think that you're seeing these people at earlier stages in their symptoms as opposed to the many years before accurate diagnosis?
Early Diagnosis and Treatment Advances
00:02:51
Speaker
You know, I think we've tried to provide education to our local health care providers. And so I think as a result of that, we are seeing patients earlier. And we're also being referred family members of individuals where there's a question of the diagnosis of HAE. So with educational efforts, we are hoping to try to see these patients earlier.
00:03:13
Speaker
Adil, would that be your experience as well that you're receiving referrals from a multitude of different physicians who are seeing patients with these symptoms?
00:03:22
Speaker
Absolutely. We get referrals from family doctors, emergency department physicians, and also other specialists. And I would agree that we're seeing patients at an earlier age. There is, I think, an increasing recognition that children can also be affected. And so a number of our new referrals are actually in children who are having their first few attacks.
00:03:49
Speaker
Things have certainly developed quite significantly in hereditary angioedema. We now have a variety of different therapies. The landscape is very different than what it used to be. So Adil, how do you decide in your treatment of these patients when to put them on long-term prophylaxis, which has certainly become the standard of care for many of our patients with HAE?
Long-term Prophylaxis and Treatment Options
00:04:14
Speaker
What are your considerations?
00:04:17
Speaker
Yeah, so long-term prophylaxis or regular treatment to prevent these painful swelling episodes is now a cornerstone of treatment. And I really like how in the present guidelines, it highlights that our goal is to normalize the lives of these patients. And that's really the goal that I have when approaching that decision.
00:04:40
Speaker
So I offer the possibility of long-term prophylaxis to any patient, and I particularly encourage patients who clearly have changes in their lifestyle, restrictions in their activities, for example, and overall decreased quality of life because of actual attacks or even fear of having attacks.
00:05:09
Speaker
So Adil, what's currently available in the treatment landscape that's going to help you meet these goals? And how do you present it to your patient, the different choices?
00:05:19
Speaker
So there are three options right now that are recommended and are considered a modern, highly effective long-term prophylaxis options. So there is a C1 inhibitor, which primarily these days is given subcutaneously, but can also be given intravenously. There is a Lana delumab, a biologic targeting plasma calicrine.
00:05:42
Speaker
And then there is an oral plasma calicron inhibitor that was the most recent addition called durotrol stat. When I'm offering a patient long-term prophylaxis, I'll go through all three options with them and discuss the advantages and disadvantages in each. And then I let them decide what they think will most fit in their concept of living a close to normal life.
Patient Acceptance of Prophylaxis: Addressing Misconceptions
00:06:07
Speaker
And Adil, any barriers would you say in getting them to accept this notion of long-term prophylaxis? Do any of them give you an argument saying, oh doctor, this makes me think that my disease is more severe, I'm not yet ready? Or do they embrace it pretty readily?
00:06:24
Speaker
I find that it can be quite variable. Certainly the patients that are having frequent severe attacks are very much interested in using treatment to prevent them, but the patients that are having less frequent attacks but still have significant impairment in their quality of life.
00:06:44
Speaker
They can be quite resistant to considering long-term prophylaxis. And often they do say that if I'm just treating when I need to, I feel like I'm not as ill or I don't have a disease. Whereas if I have to take something regularly, then I feel like I have a chronic disease. So that I think is an ongoing issue and something that we have to consider when we're counseling our patients.
00:07:12
Speaker
No, for sure. And it's interesting how the majority of our Canadian patients are on long-term prophylaxis. So clearly this has been a benefit for the majority. Dawn, what do you think? How do you present the case for long-term prophylaxis to your patients?
00:07:28
Speaker
I mean, it's interesting because the other thing that I often see in patients is that by the time they've received their diagnosis, in some circumstances, they've almost normalized the unpredictability of living with HAE and sometimes it requires multiple discussions to actually convince them that they can derive benefit from long-term prophylaxis. But once we actually have that conversation and they start, most of them don't want to stop because all of a sudden they see how a normal life can be and they're no longer burdened by the unpredictability of the attacks.
00:07:58
Speaker
Do you meet resistance from any patients when you try and explain the concept of long-term prophylaxis?
00:08:05
Speaker
Patients are open to the idea of long-term prophylaxis. We often will explore their disease experience, what their goal is in starting treatment, what they would like to see their future look like, and then we try to actually match their treatment goals with what we have available to them. Patients are always given an opportunity to reevaluate and ensure that they're satisfied with that option. If not, then we can always reconsider something else.
00:08:32
Speaker
Yes, I completely agree. One thing I always mention to patients is that the best treatment option for you right now may not be the best treatment option for you down the road. We should continue open discussions at each appointment and switching from one therapy to another should be encouraged if we feel like you're going to benefit more from something else. No, I agree with both of you totally. This is something that should come up for discussion at every visit
00:09:00
Speaker
people's needs change, their lifestyle change, their expectation of what they're hoping to achieve changes.
Unmet Needs and Psychosocial Impact of HAE
00:09:06
Speaker
So certainly nice to have choice and to be aware of all these quality of life issues. Clearly we do have good effective therapies at the present time, but what do you still think are the unmet needs in hereditary angioedema?
00:09:28
Speaker
What are the gaps? What do your patients speak to you about, about living with the disease? Though clearly it's better than it's ever been.
00:09:36
Speaker
Yeah, I totally agree. I think that there's still a huge gap around diagnosis, as we've talked about before. You know, HA is often mistaken for other types of swelling, like allergies and anaphylaxis. And so that results in delayed recognition and inadequate treatment. But we're also lacking the ability to do genetic testing, which is limiting our ability to improve diagnostic certainty and even identify other potentially affected family members.
00:10:05
Speaker
But I think that the other big unmet need from my perspective is just the high burden of illness and how it impacts their psychosocial well-being. You know, we know that patients and caregivers lose a lot of time from work and school. It can have an impact on their education, their career aspirations.
00:10:22
Speaker
And I think that a lot of us don't have the resources or the services to appropriately address the psychosocial burden of illness. I think we do a much better job of managing the clinical symptoms and controlling the swelling. But I think we also need to focus on sort of a more holistic approach and looking at the other aspects of living with HAE. I think that those are excellent points and especially, you know, the issue of passing on this disease to children since it is autosomal dominant.
00:10:49
Speaker
in most cases is something that patients speak about very frequently. Adil, would you agree with those unmet needs and the burden of illness? Is this what you're seeing in your patients as well?
00:11:01
Speaker
Absolutely. Yes, I completely agree. I think it's easy for us to think of the disease entirely as the episodes of swelling that patients experience, but the condition affects patients in ways that are far beyond that. And understanding that from a holistic perspective, I think is very important to establish rapport with patients and then also to make treatment decisions. I would agree completely.
00:11:26
Speaker
And what would it take in your opinion to address some of these issues better as clinicians? Is it the use of tools to assess quality of life? Is it just a conversation? Is it soliciting mental health support for these patients? Is it all of the above? Dawn, do you want to tackle that?
00:11:47
Speaker
Yeah, I think it's all of the above. I mean, I think that we need to get a perspective from the patient's viewpoint as to how it's actually impacting their day-to-day life and see whether there are resources available that we can access that can help them work through that using specific quality of life tools as a more validated assessment of the impact that HA is having. Are you using those regularly in your clinic?
00:12:11
Speaker
we are using quality of life assessments. We're fortunate to also have the support of a psychologist and so we do rely on her expertise to help us and navigate that landscape with patients. Yeah, I think that's great. You're ahead of the game of some centres for sure. What about you, Adil? What do you think your needs are in order to address some of these issues? What do you have and what is the ideal
00:12:36
Speaker
I think the ideal is to have strongly integrated mental health care, a lot like what Don described. In our clinic, we have access to a social worker who has some training in providing counseling. And we also have found it helpful to use the standardized patient reported outcomes to assess quality of life. But in general, the utility of those I find is really to open up the conversation with patients
00:13:05
Speaker
rather than in the number, in the score that they might get. So for instance, in the Antedema Control Questionnaire, one of the questions is about fear of having attacks. And in someone who has not had an attack for years, sometimes we still see that they are quite afraid of that. And that gives us an opportunity to explore that further.
00:13:32
Speaker
We've certainly had some excellent developments in treatment over the years, but give us an overview of what's coming.
Exploring New Therapies and Future Possibilities
00:13:40
Speaker
What are the emerging therapies that are going to come to Canadians living with this diagnosis?
00:13:46
Speaker
So most likely the next treatment that will receive Health Canada approval will be Gerdazimab. The phase 3 study Vanguard reported results earlier this year, which were strongly positive. This is an interesting drug in that it's a biologic or monoclonal antibody that's given subcutaneously once per month.
00:14:09
Speaker
which is potentially an improvement if patients find frequent injections bothersome, and its mechanism of action is different. So this inhibits factor 12a rather than plasma calicron. The results of the phase 3 study were quite encouraging, and so I expect it will be a welcome addition to our armamentarium.
00:14:33
Speaker
Excellent and anything beyond that that you think the future holds in terms of upcoming therapies? Will we have a gene therapy or something emerging?
00:14:43
Speaker
The next treatment that is in the pipeline, whose phase three study is just about completed, is for an antisense oligonucleotide technology. The investigational product is called Donut-Lorson, and this blocks plasma calicrine at the messenger RNA level.
00:15:05
Speaker
So that is also a new treatment with a different mechanism of action that could potentially be quite valuable. We'll have to see what the results of the phase three study show. And then, as you mentioned, we do indeed have a number of gene therapy technologies that are in the pipeline.
00:15:23
Speaker
And the goal for those treatments is to potentially offer a cure where patients might get a single treatment and then no longer be at risk for hereditary angioedema attacks. There's still a long way to go for some of those products. They're currently in early phases like phase two, but I think it definitely gives our patients a lot of hope.
00:15:48
Speaker
Dawn, how do you see this affecting how you practice? I mean, clearly we're going to have access to a once monthly monoclonal garidissimab. Is it just going to be part of the armamentarium? Will that help address some of the gaps of treatment burden that you spoke about earlier?
00:16:07
Speaker
Yeah, I think it's an exciting time to be involved in HAE care.
Choosing the Right Therapy for HAE Patients
00:16:12
Speaker
I think that the future is bright with some of these new options, but I think it also puts emphasis on the fact that our clinical encounters with patients really need to focus on tailored therapies and shared decision making.
00:16:23
Speaker
In our clinic, we try to focus our discussions at each clinic appointment on patient satisfaction. We review the different options for long-term prophylaxis and on-demand therapy. And we do find that sometimes patients will come with a specific therapy that they want to discuss, particularly if they're well engaged in the patient advocacy groups or if they have peers who've been on certain treatments that may spark their interest to consider other options.
00:16:48
Speaker
But I think, you know, a good example of the importance of choice is what we've seen with some patients who've been reluctant to long-term prophylaxis because up to recently, it's primarily been injectables. They're plasma products that we discuss. And so the availability of an oral plasma calico inhibitor for long-term prophylaxis has been very attractive for some patients.
00:17:08
Speaker
And for some of those that have been resistant to initiating long-term prophylaxis, we've actually found that they've become more engaged and they've actually taken out that therapy to help to control their symptoms better.
00:17:21
Speaker
My experience has been very similar that a number of patients that felt long-term prophylaxis was too burdensome definitely found that an oral treatment option that was effective was very attractive. Many people take at least one pill a day and it's very much normalized within society. And so I feel like they don't see themselves as having a severe chronic disease if that's what our treatment looks like.
00:17:49
Speaker
Yeah, I think that's an excellent point. Any parting words from both of you? I think that the landscape for HAE management is quite exciting and it's great to be able to offer patient choice and to focus not only on addressing the burden of illness, but also to focus on the burden of treatment and make sure that patients are able to live their best lives and aren't limited by having a diagnosis like HAE. Anna Dill, last word to you.
00:18:17
Speaker
I think that patients have a lot to be encouraged by with these existing treatment options and new treatment options to come. Hopefully in another five years or 10 years, we'll be talking predominantly about cures.
00:18:32
Speaker
Excellent. A very interesting and informative discussion.
Conclusion: The Future of HAE Treatments
00:18:37
Speaker
I think that this prospect of even talking about cures is extremely exciting. I want to thank both of our speakers for sharing their expertise with us. Thanks for having me. Thank you. Thank you for joining us for this episode of Science for the Real World, sponsored by BioChrist and produced by Catalytic Health.