Despite preventive treatment, on-demand meds still needed in HAE
But real-world study finds 1 in 3 were attack-free for at least 1 year
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Long-term preventive therapy can keep people with hereditary angioedema (HAE) free from swelling attacks requiring treatment for extended periods, according to a real-world study in Germany that found that more than one-third of HAE patients on prophylactic meds had no attacks needing on-demand treatment for at least one year.
Still, many individuals were shown to require on-demand treatment to manage attacks, per the analysis, which used data from German medical claims and patient charts.
The analysis showed that, among more than 75 people with HAE who started long-term prophylaxis, or LTP, 36% had no attacks during the first year. The other roughly two-thirds of the tracked patients had at least one, with the first treated attack occurring after a median of about four months following the start of preventive therapy.
The researchers say their study “provides real-world evidence on LTP use in Germany” and concluded that the data “[demonstrate] that a substantial proportion of patients continues to experience treated attacks despite prophylaxis.”
Per the team: “These findings highlight the importance of ongoing monitoring, individualized treatment optimization, and continued access to [on-demand treatment]” for people living with HAE.
The study, “Long-term prophylactic treatment and related real-world outcomes of patients with hereditary angioedema in Germany: A retrospective analysis of German claims and medical chart data,” was published in the World Allergy Organization Journal. It was funded by CSL Behring, which developed and markets Haegarda (human C1-INH), an approved prophylactic treatment for HAE. Two of the six study authors are employed by CSL Behring.
HAE is caused by genetic mutations that affect the production or function of the protein C1 esterase inhibitor, called C1-INH. Without enough working C1-INH, the body produces excessive amounts of bradykinin, a signaling molecule that makes blood vessels leaky. This causes fluid to build up in nearby tissues, triggering episodes of swelling that can affect virtually any part of the body. In this hereditary form of angioedema, people are born with these mutations.
Treatment for HAE typically involves taking on-demand medications to stop attacks and using short-term preventive therapies before known attack triggers, such as surgery. Many people use LTPs to prevent recurrent attacks.
Data suggests shirt toward oral and injection meds
LTP options include C1-INH replacement therapies such as Haegarda, which is given by subcutaneous, or under-the-skin, injection, or Cinryze (human C1-INH), administered intravenously, or directly into the vein. Other treatments block kallikrein, a protein involved in bradykinin production. These include Takhzyro (lanadelumab), also given via a subcutaneous injection, and the oral therapy Orladeyo (berotralstat).
“Although clinical trials have demonstrated the clinical efficacy and safety of currently available LTP therapies, evidence on their use in routine clinical practice remains limited,” the researchers wrote. “In particular, real-world data describing treatment sequencing, treatment persistence, switching patterns, health care resource utilization (HCRU), and the economic burden associated with LTP are scarce.”
To address this knowledge gap, the research team analyzed health insurance claims from two German statutory health insurance databases, identifying 77 people with HAE who started LTP between 2019 and 2023. The claims data were then used to examine treatment patterns, switching, on-demand medication use, and healthcare use.
Among the patients, 30 (39%) initially received intravenous C1-INH, while 24 (31%) started Takhzyro. Another 16 (21%) received subcutaneous C1-INH, while seven (9%) started Orladeyo.
Most stayed on their first treatment, but 27 (35%) switched during follow-up. Takhzyro was the most common second treatment, used by 19 (70%) of those who switched, followed by subcutaneous C1-INH in five (19%) and Orladeyo in three (11%).
No one switched to intravenous C1-INH, suggesting a shift toward subcutaneous and oral options, according to the researchers.
The scientists said this may reflect the “reduced treatment burden and improved convenience for patients” provided by these treatment types, although other factors may have contributed.
Preventive treatment did not eliminate need for on-demand meds
Overall, LTP did not eliminate the need for on-demand treatment, the data showed. Because insurance claims do not directly record HAE attacks, the researchers used prescriptions for on-demand medication to estimate the occurrence of treated attacks. By this measure, 36% of participants had no treated attacks during the first year of LTP, while nearly two-thirds had at least one treated attack.
“Our analysis … indicated that a considerable proportion of patients with HAE undergoing LTP continued to require inpatient care, with between one-fifth and nearly half of patients experiencing at least [one] HAE-related hospitalization during the observation period,” the researchers wrote.
The median was one treated attack per person, and the first occurred after a median of 114 days, or just short of the four-month mark, in one database, and 132 days, or nearly 4.5 months, in the other. Attack rates were somewhat lower in the second year, although fewer people had been followed that long.
Our analysis … indicated that a considerable proportion of patients with HAE undergoing [long-term prophylaxis] continued to require inpatient care, with between one-fifth and nearly half of patients experiencing at least [one] HAE-related hospitalization during the observation period.
The researchers noted, however, that the prescription data may have made attacks look more frequent than they actually were. About 30% of apparent first-year attacks were recorded on the same day LTP was started. The researchers said some data may reflect attacks occurring before treatment had reached its full preventive effect, or refills after attacks that prompted LTP initiation, rather than true breakthrough attacks during established treatment.
To check how well prescriptions reflected actual attacks, the researchers separately reviewed medical records from 20 HAE patients. Prescription records estimated more treated attacks than were documented in the charts in 35% of cases. While 80% had no treated attacks documented in their medical records, 45% appeared free from treated attacks based on prescription data. The researchers, therefore, cautioned that prescriptions are a useful but imperfect way to estimate treated attacks.
HAE also continued to carry a healthcare burden for patients even with LTP, according to the researchers. Over a mean follow-up of about 3.5 years, HAE-related hospitalizations occurred in 22% of people in one insurance database and 42% in the other. Among those with available work-absence data, 44% had at least one HAE-related sick leave, while medications accounted for most direct healthcare costs, the team noted.
Overall, although LTP was associated with “prolonged periods without treated attacks in many patients,” breakthrough attacks, hospitalizations, and healthcare costs persisted, the researchers noted. The team wrote that their findings highlight “the need for optimized LTP strategies and individualized treatment monitoring.”
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