Access to preventive treatment for HAE attacks limited: Brazil study
Researchers urge early genetic testing
Many patients in Brazil lack access to first-line treatments such as Takhzyro (lanadelumab) to prevent swelling attacks in hereditary angioedema (HAE), a study found.
“Despite recent advances, access to first-line therapies for long-term prophylaxis of HAE attacks remains limited,” the researchers wrote. These limitations “may likely be encountered in other areas of the world,” they wrote. “Based on the experience gained with our study, we strongly suggest early genetic testing for patients with a presumptive diagnosis of HAE if available.”
The researchers also showed that available genetic testing allowed for the identification of a significant proportion of people with HAE caused by mutations in the F12 gene, a less common cause of the disease.
“The findings underscore the urgent need for broader access to first-line therapies to all patients with HAE as a public health priority,” they wrote.
Looking at registry data
HAE is commonly caused by mutations in the SERPING1 gene, which impair the production or activity of the C1 esterase inhibitor (C1-INH). This results in excessive bradykinin production, which causes blood vessels to widen and leak fluid into nearby tissues, triggering swelling attacks. Less frequently, people with HAE have normal C1-INH levels, and the disease is caused by mutations in other genes. Those include the F12 gene, which provides instructions for making a protein called clotting factor 12 that helps control bradykinin production.
The study covered data from the first 820 participants enrolled in the physician-based Brazilian Multicenter Registry of Hereditary Angioedema (HAE), an effort aimed at identifying knowledge and management gaps in HAE and improving patient care and outcomes.
Most participants were adults (85.9%), female (68.8%), white (59.2%), and had HAE caused by C1-INH deficiency (72.4%). Thirty-nine mutations in the SERPING1 gene were identified among people with HAE-C1INH: 33 previously known variants and six novel ones. HAE with normal C1-INH levels was diagnosed in 27.6% of the participants and was mainly linked to F12 mutations (19.4%).
“Genetic testing performed early in the investigation of patients with recurrent angioedema … may enhance diagnosis and improve management, especially for patients with HAE [and normal C1-INH levels],” the researchers wrote.
Most participants had symptomatic disease (93.9%), with a mean age at symptom onset of 13.6 and a mean time to diagnosis of 12.9 years. The time to receive a HAE diagnosis was shorter in children and adolescents compared with adults (1.8 years vs. 14.5 years).
Swelling attacks were usually mild or moderate and mainly affected the abdomen (81.6%), limbs (81.1%), face (73.3%), and lips (61.5%). They were most frequently triggered by anxiety or emotional stress, levels of the female hormone estrogen, and physical trauma.
Symptoms began earlier for people with HAE-C1INH (age 11.2 vs. 19.4), and they were more frequently symptomatic (96% vs. 84.3%) than those with HAE with normal C1-INH levels. Patients with HAE-C1INH more frequently experienced prodromal symptoms, or signs present before a swelling attack, such as numbness or tingling sensations and weakness.
More than half the patients (52.8%) received on-demand treatment for swelling attacks using first-line therapies, most commonly Firazyr (icatibant, 47.6%). The use of second-line, on-demand medications was reported in 50.4% of the patients, and mainly included tranexamic acid and attenuated androgens, or male hormones (e.g. danazol, oxandrolone). Twenty-one percent never received specific treatment for HAE attacks.
Treatment with first-line medications was more frequent in people with C1-INH deficiency — particularly Firazyr (51.9% vs. 33.9%) — than in those with normal C1-INH. Similar results were seen for the use of androgens (28% vs. 8.9%) and fresh-frozen plasma (17.9% vs. 4%). Tranexamic acid was most frequently used in patients with F12 mutations (41.1% vs. 24.6%).
Regarding treatments for long-term prophylaxis to prevent swelling attacks, most participants (72%) received second-line therapies, especially attenuated androgens (52%). Less than 5% received first-line therapies, including plasma-derived C1-INH and Takhzyro, and 27.4% never received LTP.
Before initiating long-term prophylaxis, participants with C1-INH deficiency reported more yearly swelling attacks (17.1 vs. 10.1) and were more commonly treated with second-line long-term prophylaxis (77.2% vs. 54%), particularly with androgens. Those with F12 mutations were more likely to have never received long-term prophylaxis (46% vs. 21.9%).
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