Life quality declines as frequency of HAE attacks rises, study finds
Patients in Japan lacking prophylaxis for weekly, monthly attacks score poorly
People with hereditary angioedema (HAE) in Japan with access to on-demand therapies alone can have a high rate of attack frequency — weekly or monthly — that associates with a poorer quality of life, a study in that country reports.
Patients’ functioning, fears, and feelings of shame significantly linked with a high attack rate.
Long-term prophylaxis, treatments such as Orladeyo (berotralstat) and Takhzyro (lanadelumab), were not available in Japan when data for this analysis were collected in 2021, the researchers noted. Although both preventive therapies now are available, their high cost and the variability of HAE symptoms put a priority on careful assessments “based not only on medical symptoms, but also on an accurate understanding of patient health-related quality of life (HRQoL),” they wrote.
They expect this study will “provide a basis for future studies evaluating the effect of [long-term prophylaxis] on the clinical manifestations and HRQoL in patients with HAE.”
International guidelines favor long-term prophylaxis for HAE patients
The study, “Analysis of disease burden in patients with hereditary angioedema from Japan by patient-reported outcomes,” was published in The Journal of Dermatology. Four of the study’s seven authors are employees of Takeda Pharmaceuticals, which markets Takhzyro, and another is vice president of Hereditary Angioedema Japan.
Episodes of swelling that mark HAE are typically sudden and bodywide, although most commonly affecting the face, hands, and feet. While these attacks can be severe and painful, they also can be life-threatening when swelling occurs in the airways and restricts airflow.
Besides on-demand therapy to treat attacks, both short- and long-term preventive treatments are available. International guidelines on HAE management also stress achieve disease control and normalizing patients’ lives, goals that “can be achieved only through LTP,” or long-term prophylaxis, the researchers wrote.
For these and other noted reasons, it is important to evaluate individual symptoms and needs in order to provide the most suitable treatment.
Patient-reported outcomes offer a unique view into individual perceptions of health-related quality of life.
Researchers analyzed patient-reported outcomes measures (PROMs) and their HRQoL, with patients recruited between February and June 2021, before prophylactic access, through two HAE patient advocacy groups in the country.
PROMs used in this study included the 12-Item Short Form Health Survey (SF-12), the Angioedema Quality of Life (AE-QoL), the Hospital Anxiety and Depression Scale (HADS), and the Work Productivity and Activity Impairment: Specific Health Problem (WPAI:SHP) questionnaires.
About 45% of study patients had monthly or weekly HAE attacks
A total of 54 patients (87% women; mean age, 48) were included in the analysis. The majority (81.5%) had either HAE type 1 or 2 — caused by mutations in the SERPING1 gene — and 9.3% type 3, caused by mutations in a gene called F12. The remaining patients were unsure of their HAE type.
Slightly more than half of these individuals (56%) had annual attacks, about 28% had monthly attacks, and about 17% had weekly attacks. The most common symptom, experienced by 83.3% of the group, was swelling under-the-skin and/or in the mucosa, followed by gastrointestinal symptoms (74.1%), and swelling of the larynx, or voice box, observed in 55.6% of patients.
Patients with a higher attack frequency showed greater impairments in their health-related quality of life, as evidenced by a tendency toward lower scores in the physical and mental health parameters of the SF-12 questionnaire.
Similarly, greater HRQoL impairments with a frequent attack rate were observed with the AE-QoL. Scores of 39 and higher, indicative of moderate to large life quality issues, were reported by patients with monthly or weekly attacks. The highest (worse) scores corresponded with rankings of fatigue/mood and fears/shame.
Of the 54 patients analyzed, 28 were employed. Based on the WPAI:SHP questionnaire, patients with a higher frequency of attacks — monthly or weekly — showed a tendency for greater difficulties with work productivity compared with those with annual attacks.
Function poorer and fears or shame stronger with more frequent attacks
Monthly and weekly attack frequency significantly correlated with AE-QoL total scores. A similar correlation was observed with depression in the HADS.
Within the domains in the AE-QoL, difficulties with function and fears or feelings of shame were significantly associated with monthly and weekly attack frequencies. Nutrition also significantly associated with weekly attack frequencies.
Increased fatigue, mood changes, and concerns related to fear and shame significantly linked with higher levels of anxiety.
Physical health significantly associated with age, attack frequency (both monthly and weekly), gastrointestinal symptoms, and depression. Poorer physical and mental health, as assessed by the SF-12 questionnaire, associated with higher levels of depression.
Overall, without long-term prophylaxis, “the frequency of HAE attacks tended to adversely affect many aspects of HRQoL, especially in patients with attacks occurring once a month or more frequently,” the researchers wrote.
Further studies given the availability of long-term prophylaxis in Japan “should be conducted to enable comparison with the results of this study,” they concluded.
About the Author
