Assessing Patient-Reported Outcomes in Acute Attacks of Hereditary Angioedema: Insights from a Mixed Methods Study of Participants Receiving Standard-of-Care Treatments in a Real-World Setting.

Hereditary angioedema (HAE) is a rare, genetic condition characterized by recurrent, unpredictable tissue swelling attacks. Using patient-reported outcome (PRO) instruments, we evaluated the patient experience of HAE attack manifestations and what constitutes a meaningful change in those manifestations to support development of key endpoints in clinical trials for on-demand treatment (ODT) of HAE attacks. This non-interventional, mixed methods study included participants with HAE in the United States. During the quantitative phase, participants completed electronic PRO assessments including Angioedema syMptom Rating scAle (AMRA) and Patient Global Impression of Severity (PGI-S) and Change (PGI-C) for ≥ 1 HAE attack in real time. A subset participated in a qualitative interview within 1–2 weeks of attack resolution. The quantitative phase included 35 participants (74.3% female; 85.7% White), 20 of whom participated in the qualitative phase. Data collected from 98 non-upper-airway attacks and 35 upper-airway attacks, including laryngeal attacks (total = 133), indicated associations between PGI-S/-C scores and AMRA composite scores, change from baseline (CFB), and percentage CFB. When comparing different definitions of time to onset of symptom relief, PGI-C had greater sensitivity in detecting early symptom relief yet remained comparable to AMRA symptom relief endpoints. Interviews confirmed most participants understood the PROs and considered them relevant. By characterizing the patient experience with approved ODTs on HAE manifestations using various PROs (AMRA, PGI-C/S), these mixed methods findings may inform the inclusion of suitable PRO instruments, and selection and hierarchical structuring of PRO-based clinical endpoints, in future trials of ODTs for HAE attacks.