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Dr. Cohn:  

This is CME on ReachMD, and I'm Dr. Danny Cohn. With me today, are Thomas Buttgereit and Anna Valerieva. Our topic today is breakthrough attacks in hereditary angioedema.  

Thomas, let me start with you. What are the causes of breakthrough attacks in patients who are using long-term prophylactic therapy? 

Dr. Buttgereit:  

Danny, this is really a challenging question you're asking me. Well, when I look into my clinical practiceand clinical trials, I always see a certain proportion of patients that do not respond perfectly to long-term prophylaxis, meaning that these patients still face breakthrough attacks. And this really tells me that HAE is an unpredictable disease, also, that there are cases of difficult to treat HAE. Also, when patients tell me, why, what was the reason for the attacks, I say well, it's unpredictable. I do not know why it happened. In some cases, maybe patients also would say, well, I had a certain trigger like an infection, or I hadundergone some surgery which triggered the attacks. So there are some patient-related factors for sure, but there are also some disease-related factors in case of HAE that can causeyeah, breakthrough attacks, even in patients under long-term prophylaxis. 

Dr. Cohn:  

And Anna, do you also note these challenges in these patients? 

Dr. Valerieva: 

So, Danny, yeah.I agree that there are a certainnumber of patients that face breakthrough attacks despite effective long-term prophylaxis. Andfor some patients, we don't see any specific triggering factors, so those breakthrough attacks, they might tend to be spontaneous and not related to any specificworseningfactor that they experience. It’s just a spontaneous one. Some other patients might tend to have breakthrough attacksuponexposure to specific triggers, like emotional stress. I recently had a patient that had problems withher partner andthehealth status of her partner, and this was triggering her breakthrough attacks, while she was asymptomatic since maybe nearly three years. Andthere are also some patients that have some ongoing diseases, like infection or another disease that might contribute to having a breakthrough attack. Butdefinitely, something that I always try to investigate when I'm speaking aboutbreakthrough attacks in patients under prophylaxis, is whether there is– something that we can intervene, and this is the adherence to the long-term prophylaxis itself. Becausewhat we see, I think you would agree with me, withthose patients, is that whenthey get used to not having any attacks, they tend to either prolong the interval oftheir application of the treatmentthat isprophylaxistreatment, or they tend to skip a dose of an oral agent that they're using on a daily basis. Andthis isthe reason that most often, I face breakthrough attacks. So whether there is some problemwith adherence to the treatment. And this is something that I try todiscuss with the patients. 

Anotherchallenge for breakthrough attacksin patients under prophylaxis is that they might not be that well prepared for managing those breakthrough attacks. This is something that Isee from time to time, that patients tend to forgetto bring their on-demand therapy,or they're not so confident to apply thattherapyif it is an injectable one. 

Dr. Cohn:  

Yes, I agree.And then one more challenge is also to distinguish a true angioedema attack from other symptoms, which may also look or feel like angioedema attacks, like throat irritation or abdominal discomfort. And that can be a challenge, too. We reallylack biomarkers toconfirm that these symptoms are truly angioedema attacks.  

Well, I think this has been an excellent discussion. Thank you so much, Thomas and Anna, and I thank the audience, also, for joining us today. We hope this information will be helpful in your practice.  

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