Preventive therapy found to reduce number, not severity of HAE attacks
Patients lost fewer work or school days with treatment, study also shows
The use of preventive therapy in hereditary angioedema (HAE) was found to reduce the number of HAE attacks requiring on-demand treatment, and also had an impact on productivity, with patients losing fewer work or school days, a study in Australia reported.
However, prophylactic treatment did not seem to ease the severity of patients’ HAE attacks.
Researchers also found that individuals who were on preventive therapy experienced more attacks requiring hospitalization — most likely because they had more severe disease before starting treatment.
“This study demonstrates … that the use of modern prophylactic therapy for HAE results in reduction in attack rates,” the team wrote, adding, “Wider access to safe and effective prophylactic therapies is needed for patients living with hereditary angioedema.”
The study, “Living with hereditary angioedema in Australia: Findings from a national observational study using SMS to monitor the burden of disease,” was published in The Journal of Allergy and Clinical Immunology: In Practice.
Preventive therapy hard to access in Australia, researchers note
HAE is characterized by recurrent swelling attacks that affect the deeper layers of the skin.
The disease is mainly caused by mutations in the SERPING1 gene, which carries instructions for making the C1-inhibitor (C1-INH) protein. C1-INH blocks the activity of two proteins that promote the production of bradykinin, a signaling molecule that regulates blood pressure by promoting blood vessel dilation, or widening.
If C1-INH levels are too low, bradykinin levels can get too high, causing fluid to leak from blood vessels into nearby tissues and triggering an attack.
Existing treatments for HAE typically focus on treating acute swelling attacks when they occur — on-demand treatment — or reducing their frequency and preventing their occurrence through prophylactic therapy.
“In the last 10 years, remarkable progress has been made in the development of effective prophylactic treatments to manage attacks for patients with HAE; however, some prophylactic therapies are not widely available to all patients in Australia,” the researchers wrote.
The team noted that “access to modern prophylactic therapies is limited by cost and is often dependent on a patient experiencing an extremely high number of attacks per month before they are eligible for reimbursed treatments.”
To evaluate the burden of hereditary angioedema on patients, and its impact on their quality of life, researchers in Australia conducted an observational study.
A total of 47 people with HAE completed the study, which took place from July 2019 to November 2020. Patients were recruited via a reference specialist or the patient organization HAE Australasia.
The mean age of participants was 39.6 and nearly three-quarters (72%) were female. The average observational time was 9.1 months.
Participants received a weekly SMS asking what HAE medications they used that week, and whether they experienced an attack. Follow-up phone calls after an attack also were made, so that researchers could have access to a more detailed description of the event — including the treatment used and the attack’s impact on daily life.
A total of 2,648 SMS were sent, with 1,892 responses received (71%).
In all, 463 attacks were reported, of which 60% were treated. Several participants reported attacks (186 in total) that they chose not to treat, which were mostly mild.
According to researchers, considering the high compliance with SMS replies, “this study demonstrates the feasibility of collecting real-time data using SMS.”
Patients on certain preventive therapy had fewer lost work/school days
On-demand treatments for acute attacks included icatibant (sold under the brand name Firazyr) and intravenous (into-the-vein) Berinert, which were both approved for that indication in Australia at the time of the study. A total of 238 doses of icatibant were administered to treat 212 attacks, and 75 doses of Berinert were used to treat 67 attacks. Some attacks required several treatment doses.
A small number of participants experiencing eight or more attacks per month were using intravenous Berinert off-label to prevent HAE attacks. During the study, some of these patients transitioned to a newer preventive treatment, consisting of Berinert administered by subcutaneous (under-the-skin) injection. Patients receiving subcutaneous Berinert reported 67 attacks.
A total of four patients also received prophylactic treatment with lanadelumab (sold under the brand name Takhzyro), which was made available by compassionate access for a period of the study. Only one HAE attack was recorded in these patients.
Regarding the effects of preventive treatment on productivity, nearly 50% of the participants reported lost days due to HAE attacks. Nearly 20% of attacks resulted in time away from school or work. Altogether, more than 80 school or work days were lost due to HAE attacks.
Close to 50 of these lost days were experienced by patients who were not on any preventive treatment and were only treated for acute attacks. Those who were on intravenous or subcutaneous Berinert reported fewer lost days (18 and 11, respectively).
“We observed that patients on modern prophylaxis therapy had fewer attacks requiring either icatibant or [intravenous Berinert] and reported fewer days lost than patients in other treatment groups,” the researchers wrote.
Wider access to safe and effective prophylactic therapies is needed for patients living with hereditary angioedema.
Of the the total 463 recorded attacks, 23 (5%) required emergency department treatment, mainly due to facial and/or throat swelling. Eight of these attacks were reported in patients receiving intravenous Berinert, and another eight in those receiving subcutaneous Berinert. Four occurred among those receiving no treatment, and three in patients receiving tranexamic acid and danazol (sold under the brand name Danocrine).
According to researchers, preventive therapy did not have a significant impact on HAE attack severity.
Although further comparative studies are required to address the impact of such treatments on healthcare, “wider access to safe and effective prophylactic therapies for patients living in Australia should be a priority,” they wrote.
The team noted that the study “was a first of its kind, real-world, prospective, observational study of Australian patients living with hereditary angioedema.”