Preventive HAE treatment tied to lower care use, burden remains high
Real-world study finds adherence and persistence challenges after one year
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Long-term preventive treatment for hereditary angioedema (HAE) was associated with fewer swelling attacks requiring emergency or inpatient care, but many patients still struggle to remain on treatment and continue to experience a substantial disease burden, a claims-based real-world U.S. study reports.
Among nearly 500 people who started preventive, or prophylactic, treatment, slightly more than half met the study’s adherence measure after one year, and fewer than half remained on their original treatment without switching or discontinuing after two years. Emergency room visits and hospitalizations related to HAE attacks were lower after treatment started but remained substantial.
Current treatments leave room for improvement
The findings suggest the “need for novel treatment options with the potential to promote better persistence and adherence, improve patient outcomes, and further alleviate the [healthcare resource utilization] burden among patients with HAE,” the researchers wrote.
The study, “Real-world treatment patterns and clinical burden of patients with hereditary angioedema treated with long-term prophylaxis,” was published in the Orphanet Journal of Rare Diseases. The study was funded by Ionis Pharmaceuticals, which markets the preventive therapy Dawnzera (donidalorsen). Dawnzera was approved after the study period and was not one of the treatments analyzed.
In HAE, genetic mutations can affect the production or function of a protein called C1 esterase inhibitor (C1-INH). When C1-INH is missing or faulty, excessive amounts of bradykinin — a signaling molecule involved in regulating blood pressure and inflammation — can be produced. This causes fluid to leak from blood vessels into nearby tissues, triggering episodes of swelling.
These attacks, which can affect the skin, digestive tract, and airways, can vary widely in frequency and duration. While many can be managed at home, a U.S. survey found that roughly 35% are severe enough to require emergency room care. Among emergency department-treated attacks, about 30% ultimately lead to hospitalization.
“As such, HAE attacks can lead to a significant clinical and economic burden, as well as meaningfully impact the patients’ quality of life,” the researchers wrote.
To help prevent attacks before they occur, several long-term preventive therapies are available. Haegarda (human C1-INH), given as an under-the-skin injection, works by replacing the missing or faulty C1-INH protein. Takhzyro (lanadelumab), also given by injection, and Orladeyo (berotralstat), an oral therapy, block kallikrein, a protein involved in bradykinin production.
“Given the evolving treatment landscape, additional evidence is needed to understand the current clinical burden of HAE, as well as the use and effectiveness of [long-term preventive] treatment in the real world,” the researchers wrote.
Claims data show real-world treatment patterns
To learn more, a team of researchers analyzed insurance claims data from 499 people with HAE who started long-term preventive treatment from January 2021 through January 2024.
Participants had a mean age of 40.4 years, and 69.3% were female. Orladeyo was the most commonly used preventive therapy, taken by 51.5% of patients, followed by Takhzyro (37.1%) and Haegarda (11.4%). Among them, 449 remained on preventive treatment for more than 30 days. Participants were followed for a mean of 18 months, or about 1.5 years.
Staying on preventive treatment proved challenging. Six months after starting treatment, 61.1% of patients met the study’s adherence measure for their preventive therapy. By one year, that figure had dropped to 52.6%. Persistence, meaning patients remained on treatment without discontinuing or switching to other therapies, also decreased over time, with 58.7% still on their original therapy after one year and 46.1% after two years.
Among the 449 participants who remained on preventive therapy for more than 30 days, 68.4% met the study’s adherence measure six months after starting treatment, and 57% met that measure at one year. Likewise, 65.1% remained on their original therapy without switching or discontinuing after one year and 51.1% after two years.
Before starting treatment, 37.6% of patients in this subgroup experienced at least one HAE attack leading to emergency room or inpatient care. During treatment, that proportion was lower, at 22.9%, while attack frequency decreased from 0.82 to 0.51 per patient per year. The proportion of patients with HAE attacks treated in an inpatient setting also was lower, falling from 14% before treatment to 6.7% during therapy, and average hospital stays for these attacks shortened from 16.2 to 10.5 days.
All-cause hospital stays and emergency visits were lower after treatment started, but healthcare use remained substantial. Inpatient admissions decreased from 15.4% to 8.7% of patients, and average hospital days decreased from 2.4 to 1.7 per year. Emergency room use also was lower, from 51.2% of patients to 39.9%, and from 1.5 to 1.2 visits annually. Outpatient care remained high, with use decreasing only slightly from 21 to 19.3 days per year.
“While the benefit of [long-term prophylaxis] is well established, findings from the current study suggest that there remains a need for therapeutic options better suited to patient preference and lifestyle need that can promote better adherence and persistence to [long-term prophylaxis] among patients with HAE to ensure that they can derive a continued benefit from the treatment and achieve a durable reduction in disease burden,” the researchers wrote.
