Probably the most eagerly anticipated Saturday session, Ask the Experts, saw Professor Henrietta Farkas, Professor Anete Grumach, Dr. Teresa Caballero, Professor Connie Katelaris, and Professor Marc Riedl join Professor Markus Magerl on stage. The questions came thick and fast, with Prof. Magerl trying to keep answers below 45 seconds.

An audience member asked if her son, who has HAE but no symptoms, could be a pilot.
The consensus from the group was that this would be possible if the young man were on modern, long-term prophylaxis to ensure he was symptom-free in what might be precarious situations.

How does menopause impact on HAE?
The experts responded that menopause causes lower levels of the hormone estrogen, which may be expected to lessen HAE symptoms, but this is not the case. Like pregnancy, there can be an improvement, worsening, or no change in symptoms. We cannot predict what will happen to attack frequency during menopause, so more research is needed.

Does HAE make the person more susceptible to other diseases?
The panel agreed there are no clear associations with other diseases.

There has been some concern about a slightly increased risk of autoimmune diseases, but this was one old study. Additionally, there have been tests in animals that showed a slightly increased risk of blood clots, but this was not enough to prove it would happen in people with HAE.

A study of people with HAE and COVID showed no increased susceptibility to COVID. However, for some people, worry and anxiety about getting other health conditions did seem to impact HAE symptoms negatively.

Who takes care of the psychological aspects?
While the experts believed that psychological support should be available to all people with HAE, there was an acknowledgment that a better job needs to be done. Often, too little is done, the panel felt, to address the mental health aspects of HAE. Having psychologists and genetic counselors available can be beneficial.

Can I get a tattoo with HAE?
The panel stated that if the patient was well controlled on modern prophylaxis, absolutely yes. If the tattoo were to be around the neck region, short-term prophylaxis should be considered.

Is it possible to become addicted to HAE medication?
In the bad old days, the panel suggested, patients were treated only with painkillers like opioids. These do nothing to treat the underlying swelling, and of course, opioids are addictive. Modern HAE-specific therapies cannot cause addiction.

What’s the best treatment for a pregnant patient?
As a specialist in HAE and pregnancy, Dr. Caballero responded. She felt that plasma-derived C1 inhibitor is the only treatment advised for a pregnant patient.

If surgery is needed, do I need short-term prophylaxis even if controlled on lanadelumab?
The panel noted that there is no data from the studies to date. Their thoughts were that patients who are very well controlled on lanadelumab should not need short-term prophylaxis. However, there was caution due to the lack of data, and some experts still argued for using short-term prophylaxis. Either way, everyone agreed having acute therapy in the operating suite was really important.

What advice can you give people with HAE moving to another country?
The panel’s suggested the things to think about were:

• Insurance. Most will cover HAE, but there’s a lot of paperwork involved. Never just assume you’ll be covered.
• Talk to your current specialist. Ask them to connect you with a specialist in the new country.
• Download HAE Companion, HAEi’s app for foreign travel

If HAE is okay on androgens, should a patient be moved to modern therapy?
The panel accepted that there are still many countries with no access to modern therapy, although that is improving a lot.

With androgens, even if it’s low dose and there are no apparent side effects, there could be hidden harms such as to blood pressure, cardiovascular problems, and liver function. The primary concerns are about long-term effects such as these. The panel recommended careful monitoring for anyone prescribed androgens.

When will gene therapy be available worldwide? Will it mean the end of HAEi?
The panel took the scientific question. In general, it will likely be some years before gene therapy is available outside of clinical trials, the first of which is due to be reported in 2026. In the panel’s opinion, this will be because regulatory authorities will need to see longer-term safety data due to the permanent nature of gene medicines.

The next question will be about the cost of what are known to be costly therapies. How we pay for these treatments will be complicated.

Responding on behalf of HAEi, Fiona Wardman was clear that while HAEi wouldn’t be around if HAE were no longer around, this wouldn’t be the case. There will continue to be new mutations. Some people will have HAE, and as a result, HAEi will be there every step of the way.

This answer prompted the panel to make clear that gene therapies don’t eliminate the risk of passing the genetic mutation onto children. Even if the person treated with gene therapy no longer has HAE symptoms, their child could inherit the mutated gene. And, of course, we continue to have patients with spontaneous mutations.

Will I have attacks if I go on the gene therapy trial?
The available data shows that patients may have some attacks in the early stages. These quickly fall away, and the latest data shows an almost complete elimination of attacks.

In the new study, there is a placebo arm, which means some patients will need to treat attacks with acute treatment. These individuals will have the option to have another option after six months and may receive the gene therapy.

Why aren’t bradykinin levels measured to diagnose HAE?
Bradykinin is important in multiple forms of HAE. Historically, it’s been tough to measure. It essentially disappears very quickly once blood is removed from the body. Some laboratories have published new ways to try and measure bradykinin, so it’s conceivable we may be able to measure bradykinin levels in the not-too-distant future, perhaps to diagnose or monitor how patients are doing on treatment.

What is the role of kallikrein, and are there any effects if it’s blocked continuously?
There were worries initially about blocking kallikrein, as the impact of doing this was still being determined. However, by the end of clinical trials, even long-term ones, there were no problems seen. Also, there is evidence that kallikrein is not entirely blocked; there is still some activity.

Should every HAE patient have a genetic test at diagnosis?
The panel felt that if the patient has HAE with C1 inhibitor deficiency, the diagnosis can be confident and confirmed without needing a genetic test. However, referencing Marc’s earlier talk, the panel suggested that with some mutations, it can be challenging to differentiate types of HAE, so a genetic test can provide certainty for patients. Additionally, genetic testing for children, new or unborn, can diagnose HAE where other tests may not work.

Could a baby born with abdominal and genital edema have had an attack during a traumatic birth?
The panel felt it was hard to be sure, but it is a likely explanation.

What treatment is recommended for HAE with normal C1 inhibitor (HAE-nC1INH)?
This is, as Marc Riedl’s presentation showed, a difficult question to answer due to a lack of data. It looks like icatibant and plasma-derived C1-inhibitor work for most patients to treat attacks. Tranexamic acid is often very helpful in preventing attacks, and depending on the mutation, there may be roles for some of the more modern treatments, such as lanadelumab.

The final question to the panel was: How optimistic are you about the future of HAE?
The entire panel was clear; the answer was: ‘Very!’