Hereditary angioedema prevalence and satisfaction with prophylaxis in South Australia

Abstract

Background: Hereditary angioedema (HAE) due to deficiency of C1 Inhibitor (C1INH-HAE) is a rare, unpredictable and potentially fatal genetic disorder. There are relatively few systematic population prevalence studies, with reports from various countries of between 1 in 20,000 and 1 in 150,000. and no Australian data. The therapeutic landscape for HAE has changed dramatically in recent years with a focus on highly effective prophylaxis, with the aim of total suppression of angioedema and achievement of a normal life.

Objectives: Epidemiological survey of HAE in South Australia, with description of patient characteristics, quality of life and treatment, with a focus on prophylaxis.

Methods: Case ascertainment was conducted over 18 months from January 2021 to July 2022, using a range of approaches with the aim of identifying all people with C1INH-HAE in South Australia. Questionnaires were administered to consenting patients utilising established HAE-specific and general survey instruments.

Results: We identified 35 people with HAE in South Australia, yielding a population prevalence of 1 in 52,400, in line with average established international prevalence. HAE was identified in 4 patients of Indigenous Australian heritage. Seventeen of 31 adult patients completed an additional multi-questionnaire survey, revealing overall satisfactory disease control. Most common prophylactic therapies were danazol, lanadelumab, and subcutaneous C1 inhibitor. Many patients (mostly male) with milder disease had responded well to low-dose danazol with good tolerance and have continued to use it, whereas patients with higher disease burden are now using newer therapies, and overall satisfaction with current prophylaxis is high.

Conclusions: Prevalence of HAE in South Australia aligns with international reports. Our population survey indicates that current long-term prophylaxis therapies including danazol, lanadelumab and C1-inhibitor, applied to appropriate patients taking into account disease activity and drug risks and tolerance, are effective for HAE attack prevention and produce high levels of satisfaction.

Keywords: Angioedemas, Hereditary; Angioedemas, Hereditary/therapy; Epidemiology; Health-related quality of life.

Fig. 1

Study design and case ascertainment. South Australian population of hereditary angioedema (HAE) subjects were obtained through interrogation of medical records at the participating institution (diagnosis of HAE or presentation with angioedema), HAE specific therapy dispensing histories through public hospital pharmacies (Danazol, icatibant, C1-INH SC, lanadelumab), local health professionals both working in public and private sectors and in addition search of HAE specific diagnostic testing (C1 inhibitor quantitative and functional levels, the latter determined by chromogenic assays) through local public laboratory services

Fig. 2

Diagnostic delays, incorrect diagnoses and treatments and disease attack locations. A) Surveyed subjects (N = 17) provided detailed histories of their diagnostic odyssey, with all but one being diagnosed pre-symptomatically. B) Majority of subjects were given an incorrect diagnosis and provided an ineffectual or incorrect therapy initially before correct diagnosis and 3 subjects underwent an Appendectomy. C) The most common location for attacks in our cohort were abdominal, and extremity with facial, genital and throat being much less common. D) HAE is a highly penetrant autosomal dominant disease with many kindreds having multiple generations affected and deaths from the disease in recent memory

Fig. 3

Quality of life, disease activity and productivity scores in N = 17 surveyed HAE subjects by current HAE prophylaxis therapy. A) Angioedema control test (AECT), Hereditary Angioedema Activity Score (HAE-AS), HAE – Quality of life (HAE-QOL) questionnaire and Work productivity activity index, total workplace productivity impairment (WPAI). B) 7 subdomains of HAE-QOL. Dashed lines represent the upper and lower bounds for each questionnaire and dotted line (AECT and HAE-AS only) indicates the cut-off for low disease activity as judged by each tool. Pairwise Wilcoxon tests were applied to assess for statistical difference, applying Bonferroni correction for multiple comparisons. C1INH, C1-Inhibitor Concentrate; DZL, Danazol; LAN, Lanadelumab

Fig. 4

Therapeutic odyssey and treatment satisfaction. A) Therapeutic histories of subjects N = 17 displayed as a network graph, Sankey-plot showing progress through therapies. Connecting line colour and width demonstrate satisfaction rating of the previous nodes therapy. B) Boxplot of therapy satisfaction ratings with previous and current therapies, demonstrating progressive increase in therapeutic satisfaction with current versus previous therapies (For interpretation of the references to colour in this figure legend, the reader is referred to the Web version of this article.)

Supplemental Fig. 1

Correlation of study variables including demographics, laboratory indices, QOL questions and angioedema activity scores. Strong inter-questionnaire correlation observed between HAE-QOL, HAE-AS, AECT and WPAI measures. Colour and circle size indicates direction and magnitude of agreement, crossed out circles are statistically non-significant