Uncontrolled HAE attacks mean lower quality of life for patients
Real-world study finds swelling episodes common despite treatment
While the treatment landscape for people with hereditary angioedema (HAE) has improved significantly in the last decades, symptoms such as uncontrolled swelling attacks — occurring despite the use of on-demand or long-term preventive therapies — have resulted in low health-related quality of life (HRQoL) among patients, particularly women and those with a high attack rate.
That’s according to a retrospective analysis of real-world data, which found that poor HRQoL was common among people with HAE despite treatment, even among certain low-attack cases.
The approved HAE therapy Takhzyro (lanadelumab), available in the U.S. since 2018, was shown in clinical trials to reduce the frequency of swelling attacks among patients. However, as late as 2022-2023, when this study was conducted, the treatment was not available in many countries. This research, led by physicians at Takeda, Takhzyro’s developer, sought to understand the impact of HAE attacks from a patient’s perspective, and to identify factors that contribute to disease burden.
The researchers found that people with HAE have predominantly relied on on-demand treatment alone or long-term preventive treatment, mainly with attenuated androgens and tranexamic acid. Despite their use, many individuals had uncontrolled HAE attacks, the data showed.
Moreover, such attacks were tied to greater anxiety, a loss of productivity in work and school, and “limited career/educational achievement,” the team wrote.
According to the scientists, these study findings highlight how “relying solely on attack frequency and severity could significantly underestimate the impact of HAE on the lives of patients.”
The study, “Real-world treatment patterns and burden-of-disease of sub-optimally controlled hereditary angioedema,” was published in the World Allergy Organization Journal. The study was funded by Takeda.
HAE is a rare genetic disorder characterized by episodes of swelling caused by an overproduction of the signaling molecule bradykinin. The most prevalent forms of HAE, types 1 and 2, result from mutations that interfere with the production or function of C1 inhibitor, a protein that typically helps control bradykinin levels in the body.
Access to newer treatments remains limited for HAE patients
Despite newer treatments like Takhzyro, many people with HAE still experience swelling attacks and other symptoms. Moreover, adverse side effects from attenuated androgens — male hormones used as a preventive treatment — are also common.
For this study, the research team retrospectively reviewed real-world data from HAE patients with types 1 and 2 who had poor disease control. Their study (NCT04957641) involved individuals from 32 centers in various countries between April 2022 and January 2023.
Because Takhzyro was not available in most countries during the study period, patients on the therapy were excluded. This “gave us the opportunity to study the burden of uncontrolled disease when there are restrictions in access to recommended first-line care,” the team wrote.
The analysis included 214 patients with a mean age of 43. Slightly more than half were women. A total of 91% had HAE type 1 and 82% had a family history of the disease. Among those with other co-occurring conditions, the most common were high blood pressure, followed by allergies, anxiety, asthma, and depression. On average, these individuals had lived with HAE for 16.3 years.
The patients had reported that one of the key factors contributing to poor disease control was frequent attacks, as well as severe ones. Other factors included impaired quality of life and difficulties in attending school or work. Most patients (79%) believed that more than one factor contributed to poor disease control, but 56% were optimistic that it could improve.
Over one year, a total of 2,127 HAE attacks were reported, with an average of 9.9 attacks per patient. Most attacks (77%) were classified as moderate, with nearly half (45%) considered severe. Most patients were aware of their attack triggers, with stress and physical trauma being the most reported. The risk of attacks was significantly higher in women and younger patients — those 18 to 40 — compared with men and older patients.
On-demand treatment mostly used for HAE attacks
Nearly 90% of patients relied on on-demand treatments for their HAE, with half using them exclusively. The remaining 36% used a mix of on-demand and long-term preventive therapies for their HAE attacks.
About one-quarter of patients used attenuated androgens for long-term prophylaxis, or preventive therapy.
Physicians’ main reason for prescribing a long-term preventive therapy was insufficient control with on-demand treatments, followed by the need to improve quality of life, and the lack of adequate disease control from a previous preventive therapy.
Most patients — more than 9 of every 10 — maintained their long-term preventive regimen, with an average treatment duration of 8.1 years. Some patients discontinued long-term preventive therapies due to poor tolerability or insufficient control of attacks.
[These findings underscore] the necessity to adhere to international guidelines, promoting/recommending utilization of more efficacious and well-tolerated therapies.
Despite the significant burden of HAE attacks, those on a long-term preventive regimen had lower attack rates and experienced fewer severe attacks compared with those not on this type of therapy.
To evaluate HAE’s impact on quality of life, patients completed both a disease-specific and a general questionnaire assessing daily functioning and well-being.
As attack frequency increased, so did impairment in HRQoL, the data showed. Additionally, female patients experienced a greater impact on their HRQoL compared with males.
Many patients reported experiencing pain/discomfort and anxiety/depression, which became more common as the number of attacks increased.
Overall, according to the researchers, this real-world study shows HAE patients may still experience attacks despite treatment. The findings “[underscore] the necessity to adhere to international guidelines, promoting/recommending utilization of more efficacious and well-tolerated therapies,” the team concluded.
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