HAE type 3 tied to more severe symptoms by doctors, patients
Survey study compares types 1 and 2 disease with normal C1-inhibitor group
People with hereditary angioedema (HAE) who have normal C1-inhibitor (C1-INH) levels and activity appear to have more active disease and more severe symptoms than those with HAE type 1 or 2, a real-world study found.
These patients also “experience greater impairment to their quality of life, work, and daily functioning,” the researchers wrote, adding that “powered statistical analyses are required to confirm these findings.”
The study, “Physician- and patient-reported outcomes by hereditary angioedema type: Data from a real-world study,” was published in the journal Allergy and Asthma Proceedings. It was supported by Takeda Pharmaceuticals, the company that markets Cinryze (human C1 esterase inhibitor), an approved HAE treatment.
HAE type 3 defined in study as C1-INH with normal levels, activity
Angioedema occurs when fluid accumulates under the skin or in the mucous membranes lining the respiratory and gastrointestinal tracts, leading to swelling attacks. HAE, the condition’s inherited form, is caused by genetic mutations that result in the excessive production and release of bradykinin, a signaling molecule that causes blood vessels to become more permeable and leaky.
Unlike HAE type 1 and 2, both due to mutations in the SERPING1 gene that result in reduced C1-INH levels or activity, HAE type 3 is tied to F12 gene mutations that do not affect C1-INH.
Disease treatment usually aims to prevent and treat recurrent swelling attacks by addressing their underlying causes. Yet, according to researchers, “little is known about the differences in outcomes between patients with HAE types [1 or 2] … and those with normal C1-INH.”
Researchers compared real-world outcomes for HAE types 1 and 2 patients to those for HAE type 3 — defined in this study as having normal C1-INH, rather than by type — using data from doctors and patients. They also looked at how the disease impacts a patient’s quality of life.
Data came from the Adelphi HAE Disease Specific Program, a U.S. survey conducted between July and November 2021. Doctors reported on disease activity, symptom severity, and attack history, whereas patients shared their own experiences.
67 doctors treating HAE, 368 patients took part in 2021 U.S. survey
A total of 67 doctors and 368 patients took part. Most patients (92.4%) had type 1 or 2 disease, while 7.6% (28 patients) had normal C1-INH.
According to doctors, people with HAE and normal C1-INH appeared to have higher disease activity and severity, both at the time of diagnosis and the survey. For example, the most recent swelling attack was severe for a significantly higher proportion of normal C1-INH patients than those with HAE type 1 or 2 (34.6% vs. 4.4%). Similarly, a higher proportion of normal C1-INH patients had to be admitted to the hospital during their most recent attack than the two other HAE groups (39.3% vs. 6.6%).
“Although the burden of HAE is substantial in all HAE types, analysis of these data suggests that patients with [HAE with normal C1-INH] have higher disease activity and severity,” the researchers wrote.
HAE patients with normal C1-INH also scored poorer on assessments of health status and life quality than other patients, with a greater proportion reporting higher absenteeism, or work time missed, than those with HAE type 1 or 2 (25% vs. 2.7%).
Similar proportions of patients in both groups reported receiving prophylaxis or preventive treatment (78.6% vs. 78.5%) and on-demand treatment (92.9% vs. 86.8%). However, those with HAE with normal C1-INH had been on these treatments for an average of up to three years longer.
Plasma-derived C1-INH therapies, including Cinryze and Haegarda, were the most common prophylactic treatments for HAE with normal C1-INH (36.4%) and HAE types 1 and 2 (49.4%). With on-demand treatment, Ruconest (recombinant C1 esterase inhibitor) was most frequently prescribed for HAE patients with normal C1-INH (34.6%), and bradykinin inhibitors were the most common choice for HAE types 1 and 2 (44.1%).
Both patient groups showed improvements in disease activity and severity between the time of diagnosis and the survey.
“Regardless of HAE type, the patients had reductions in disease activity and severity from diagnosis to the time of data collection,” the researchers wrote.
Two of this study’s eight authors were Takeda employees at the time of this work, and its findings were presented at the 2022 annual meeting of the American College of Allergy, Asthma & Immunology.
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