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Common Questions in HAE
Improving Patient Outcomes in HAE Care: Expert Takeaways to Your Frequently Asked Questions

Released: February 17, 2026

Marc Riedl
Marc Riedl, MD, MS
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Key Takeaways
  • Initiating long-term prophylaxis for HAE requires in-depth, patient-focused discussions about the available options, weighing the burden of HAE attacks against each treatment’s characteristics.
  • Selection of long-term prophylaxis therapy for patients with HAE should be driven by several important factors, including efficacy, safety, tolerability, and patient preference.
  • Based on available evidence, patients with HAE should continue to receive short-term prophylaxis therapy for planned invasive medical procedures even if they are taking long-term prophylaxis.

In this commentary, Marc Riedl, MD, MS, answers questions posed by healthcare professionals (HCPs) during a live symposium titled “Future-Proofing in HAE: Advances in Long-term Prophylaxis to Prevent Attacks and Improve Quality of Life.” Learn how to help patients with hereditary angioedema (HAE) select the best treatment for them, why short-term prophylaxis is still necessary for those taking long-term prophylaxis therapy, and strategies for switching patients’ treatment from on-demand to long-term prophylaxis therapy.

What considerations should HCPs keep in mind when selecting plasma kallikrein inhibitors or other long-term prophylaxis therapies for patients with HAE and comorbidities or unique risk profiles?
This brings into consideration the mechanisms of action of each long-term prophylaxis therapy. They are different, and we are seeing more introduced as additional novel treatments become available. In general, I do not have strong recommendations about which specific mechanisms of action work best for patients with HAE. Of more importance, treatment selection truly is a matter of determining which therapy is most effective, safe, and tolerable for each patient. Fortunately, we have not seen concerning class-wide adverse effects for the long-term prophylaxis therapies that would require HCPs to consider major safety risks for specific populations. The short answer to this question is no. For HAE due to C1-inhibitor (C1INH) deficiency, I do not think there is a specific patient population who would benefit more from a kallikrein inhibitor vs C1INH replacement therapy vs factor XII inhibitor.

Ideally, HCPs should determine which therapy is going to work best for each patient. Furthermore, safety profiles should be something HCPs counsel patients about with all medications, including the oral agents. There can be some drug interactions with small-molecule drugs, which are true for both berotralstat and sebetralstat. In HAE management, treatment-related drug interactions are newer concerns as we don’t generally see these with the biologics, so we must be watchful for these, particularly in patients who are taking the oral therapies. That said, I do not spend much time considering the mechanisms of action of each HAE therapy when engaged in shared-decision making with patients, but some patients are interested in this information. Rather, I focus on each agent’s efficacy, safety, dosing regimen, and other particular considerations related to the patient in front of me.

How do you approach shared decision-making with patients interested in initiating long-term prophylaxis therapy, especially among those who are hesitant to switch from an on-demand therapy?
This is important and can be challenging, particularly because HCPs are all busy in their respective offices and/or clinics. That is, time spent with patients is a premium for us, and these shared decision-making conversations are lengthening as more treatment options become available. As new therapies are added to our toolbox, my goal is to cover all of them with patients as best I can. Furthermore, I find that patients typically hone in on a couple of options based on their preferences and interests, so we will spend more time discussing those. I honestly do not think there is a shortcut to this. HCPs must ensure patients know about their options and then quickly try to narrow down the list as far as switching from on-demand to long-term prophylaxis therapy. I do not find that to be too challenging, as most of my patients already have some interest in long-term prophylaxis. This is especially true for those experiencing frequent or severe HAE attacks. They often are thankful for the on-demand therapy, but they also struggle to do their normal activities with this treatment. So many times patients are initiating these conversations with me.

Of note, I certainly discuss long-term prophylaxis with every patient even if they are not interested right away. They might become interested in it in the future because HAE can change and affect their lives differently as time goes on. There are patients who do not want to use a chronic therapy, and that is absolutely fine. But HCPs should be discussing the benefits and predictability that may be achieved by preventing HAE attacks with long-term prophylaxis therapy. If patients are still comfortable with their on-demand therapy, great, we can do that, too. We just need to optimize that particular treatment approach.

For patients with acquired C1-INH deficiency, what therapies would you consider using for their new onset and troublesome angioedema?
Acquired C1-INH deficiency has similar symptoms to HAE but is due to an underlying condition like lymphoproliferative disease or an autoimmune condition, where patients’ C1-INH is consumed or metabolized. These patients often present with low levels of C1-INH and C1Q—a distinguishing laboratory result compared with HAE. To be clear, none of the therapies mentioned in this commentary have been formally studied for acquired C1-INH deficiency. Rather, this condition requires off-label treatment.

The data that are published suggest that plasma kallikrein inhibitors and bradykinin B2 receptor antagonists work acutely and preventatively for acquired C1-INH deficiency. That also is represented in anecdotal experiences via case reports after treating a fairly large number of patients with acquired C1-INH deficiency. The challenge is working with health insurance companies because these treatments are considered off-label despite the good reasons we have to use them to prevent or treat life-threatening attacks. The 1 difference to note is that C1-INH concentrates may not be as effective over time because autoantibodies that form via the acquired C1-INH deficiency may neutralize and reduce the efficacy of these therapies. Over time, patients with this rare condition might become more tolerant and require higher doses of C1-INH concentrate to see a benefit. Again, it is a matter of assessing patients and discussing their preferences with them. Use the tools you have to help patients and understand that we do not have the same level of efficacy and safety data for acquired C1-INH deficiency as we do for HAE.

What long-term prophylaxis therapies are available to younger children and adolescents with HAE?
This is an important question because pediatric HAE is an area where we have not had as many treatment options become available. Two respective studies for lanadelumab and berotralstat evaluated these agents’ efficacy and safety among pediatric patients with HAE, which led to both being FDA approved to prevent HAE attacks in patients 2 years of age or older. In addition, there are 2 C1 esterase inhibitors—one is administered subcutaneously and the other is administered intravenously—that are FDA approved for routine prophylaxis against HAE attacks in patients as young as 6 years old. We have some options, but many of the novel HAE therapies are only approved to treat patients 12 years of age or older, which limits our treatment options for younger children with HAE.

Although many children with HAE do not have frequent symptoms or are asymptomatic, there are some who are quite symptomatic. HCPs must look at their options and know which therapies can be used in younger patients. Of course, the treatment burden for children will be different, too. I look forward to potentially having oral options for these children because injections and infusions are difficult and burdensome for them. Finally, being a teenager is difficult enough for some patients, so you can run into adherence issues with those who do not want to take their therapy or are struggling with a stigma attached to either their disease or treatment. Therefore, trying to negotiate and talking with younger patients and teenagers as well as their parents will help in determining what will work best for them. Sometimes that is an oral therapy; sometimes the frequency of an oral therapy is too much and patients are better off with a less frequent, subcutaneous treatment that provides long-term prophylaxis. Again, there are no hard and fast rules. HCPs must be knowledgeable about their options and individualize treatment to each patient, including younger children and adolescents.

Have you experienced any difficulties with getting your local hospitals to stock C1-INHs for unexpected and acute management needs?
Absolutely, this is still a thorn in our side. It is quite unusual for hospitals to have access to C1-INHs or any HAE-specific rescue medication. I am fortunate in my health system because we can facilitate that access, but most hospitals that patients travel to do not have a C1-INH on hand. If there is a need for rescue treatment or short-term prophylaxis therapy prior to a surgery, we often struggle to get that access in a timely fashion. With some lead time, you can see success with getting C1-INHs to patients. But these therapies must be expedited through patients’ health insurance plans. And as we all know, that does not always happen quickly. That is why HCPs should ensure patients know that we need some lead time for providing short-term prophylaxis therapy. If the situation is due to a trauma or unexpected event, there is nothing we can do about that. But if there is a planned procedure, we need time to get the therapy into our patients’ hands and discuss their needs with the anesthesiologist or surgeon. It is unusual to have these therapies just sitting in the hospital pharmacy, so we have to overcome this barrier.

Of note, we do not have enough data to know if short-term prophylaxis is absolutely necessary for patients who are on effective long-term prophylaxis therapy. We need validated data; therefore, HCPs should still err on the side of caution with using short-term prophylaxis therapy among those on long-term prophylaxis. Hopefully, we will have more data to answer this question in the near future.

How would you transition patients from oral to injectable HAE therapies and vice versa?
I think the way that HCPs should approach therapy transitions is to look at the half-life of the current agent patients are taking and then consider how to transition them to the appropriate long-term prophylaxis. There are several articles available that discuss data on switching HAE therapies and can guide your treatment options. For example, a study reported data on patients who switched from lanadelumab, berotralstat, or a C1-INH to donidalorsen. Researchers gave patients their last dose of lanadelumab 14 days prior to their first dose of donidalorsen. For those on berotralstat or a C1-INH, they continued these therapies for 14 days after the first dose of donidalorsen. That study provided an example algorithm that can be used for switching to donidalorsen. Other studies have provided data on patients switching between long-term prophylactic therapies, but with less prescriptive specific algorithms.

How can HCPs improve HAE treatment adherence, especially among patients who had poor adherence to prior therapies?
Poor adherence should trigger HCPs to ask the question: what is the barrier from the patient’s perspective? For example, do they feel it is because they are taking an oral therapy and they tend to miss doses because of daily dosing? That is a discussion for HCPs to have with patients who are considering injectable therapies as well. We must address any fears they may have about injections, including the pain associated with it or dosing frequency. If patients report injection fatigue, can we offer them another injectable with a longer dosing interval or an oral option? I think poor adherence has many different factors. But if it is related to the delivery system or the dosing interval, these things can be assessed and adjusted as needed.

For those HCPs who see 1 or 2 patients with HAE, would they be better served at a larger, HAE-focused facility?
That decision is up to the respective HCP. I believe that if HCPs learn what is needed and are interested in HAE, anybody can do a good job at managing patients’ care. It takes effort and interest, and not everybody understands right away; it takes some time. HAE may not be as simple to treat as some other diseases/conditions. I think that allergists and immunologists generally are capable of providing this care. And although it has gotten more complicated, there are guidelines now to help guide our efforts.

Your Thoughts
How often do you use shared decision-making when discussing treatment options with your patients with HAE?  You can get involved in the discussion by answering the poll question and posting a comment below.

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