Hereditary Angioedema Prophylaxis: Persistence and Adherence

Advances in hereditary angioedema attack prophylaxis have provided more options for patients than ever before, with multiple agents available for long-term prevention.

“The treatment landscape for hereditary angioedema is evolving rapidly, with several long-term prophylaxes approved in the last decade,” and more on the horizon, said William Lumry, MD, of AARA Research Center in Dallas. “Over time the treatment burden has gone down significantly. … And now we’re starting to see more extended-interval drugs.”

These preventive medications include:

• C1 esterase inhibitor (Haegarda) approved in 2017 for subcutaneous injection every 3-4 days
• Plasma kallikrein inhibitor lanadelumab (Takhzyro) approved in 2018 for subcutaneous injection every 2-4 weeks
• Plasma kallikrein inhibitor berotralstat (Orladeyo) approved in 2020 as a once-daily oral capsule
• Anti-factor XIIa biologic garadacimab (Andembry) approved in 2025 for subcutaneous injection once monthly
• RNA-targeted therapy donidalorsen (Dawnzera) approved in 2025 for subcutaneous injection every 4 or 8 weeks

And real-world data show that patients are taking advantage of those options, sticking with a medication typically less than 2 years.

Those were the findings Lumry reported from an observational study presented in March at the American Academy of Allergy, Asthma & Immunology annual meeting.

His analysis of the Komodo Research Database of insurance claims to more than 150 payers covering over 170 million persons included 499 patients age 12 and older who started on one of the newer long-term prophylaxis drugs for hereditary angioedema from January 2021 through January 2024 and had at least 12 months of continuous coverage prior to initiation. The study examined data for C1 esterase inhibitor, lanadelumab, and berotralstat but didn’t include garadacimab or donidalorsen, which had not yet been approved during the study period.

During follow-up, 11.2% of patients switched their long-term prophylaxis medication, and 30.5% discontinued their initial medication. Median time to switch or discontinuation was 20.8 months, with 58.7% persistent at 12 months and 46.1% persistent at 24 months across the three drugs.

In terms of adherence, mean proportion of days covered by a prescription fill at 12 months was 66.7%. The proportion at 12 months considered adherent due to at least 80% of days covered by a prescription to the index prophylaxis was lowest at 32.3% with the C1 inhibitor, followed by lanadelumab at 52.3%, and berotralstat at 56.2%. One of the limitations of the study was that it could determine only medication dispensing without data on whether patients actually took their medication.

A similar study presented at the Eastern Allergy Conference in 2025 with insurance claim data on 357 patients initiating the same three drugs from June 2017 through September 2023 showed similar results, with 61%, 58%, and 53% persistence on treatment at 12 months for berotralstat, lanadelumab, and the C1 inhibitor, respectively. Proportions of days covered were 73%, 78%, and 74%, respectively.

“It’s a chronic disease, it’s very disruptive, it’s potentially life threatening. Why would you stop the medication? We don’t have the answer for that. But the point is that they do,” Lumry told MedPage Today, “suggesting that you either need a drug that’s easier to take, less treatment burden, or maybe that works better.”

“Part of it is just lack of efficacy: ‘I’m not getting the effect that I want,'” he suggested. The two injectables have shown a reduction in attack rates of 80-95%, whereas berotralstat’s pivotal trial data showed a 44% attack reduction.

“The other issue is there are, at least in the first couple of months, some side effects that will knock people out,” Lumry noted, particularly gastrointestinal symptoms. “So they’ll just stop because of the side effects.”

With berotralstat as an example, he said, an off-label way some physicians use to try to prevent the roughly 15% drop-off within the first couple of months is to dose every other day for a couple of weeks until patients get adjusted to it and then go up to full dose, or to start at a lower dose, 110 instead of the usual 150 mg.

For adherence, oral drug recipients can benefit from pill boxes and injectable users can adopt other strategies that can remind them to take their medication as prescribed, Lumry added. Less frequent injections and formulations that are less painful to inject (without citrate, for example) might also help, he said.

The newest drugs approved for long-term prophylaxis and others in late-stage development might also shift the landscape on persistence and adherence, Lumry noted. “And so we’ll see what impact those longer-interval, maybe less side effects, more efficacious drugs have.”