Attack severity in hereditary angioedema: a qualitative study to inform future economic evaluations

Hereditary angioedema (HAE) is a rare condition with unpredictable, potentially life-threatening swelling attacks. Severity classifications in economic evaluations of new treatments often rely on parameters such as attack duration or ADL limitations, potentially oversimplifying patient experiences and undervaluing treatments. This study aimed to explore how adults with HAE define attack severity, including the role of attack location and attack phase, to inform the characterization of attack severity in cost-effectiveness evaluations.

Semi-structured qualitative interviews were conducted with US adults with HAE, purposively sampled with quotas for attack severity and attack locations. Participants were asked to describe their HAE attacks, in terms of symptoms and HRQoL impact and how they defined attack severity. Interviews were thematically analyzed, participants also completed the EQ-5D-5L.

A total of 25 adults with HAE took part in the interviews. Participants' severity classifications demonstrated location-specific impacts: throat attacks were almost universally severe due to mortality risk, abdominal attacks were also generally severe due to incapacitating pain, whereas the severity of face, genitals and hand attacks was driven by psychosocial or functional burdens. Prodromal, main, and recovery phases each also contributed to perceptions of severity, with longer durations being considered as more severe.

Severity assessments, including the length of attack phases, were reported retrospectively, which may be subject to recall bias. Overall, patient-defined severity, shaped by location, phase, and context, challenges simple severity classifications and indicates that severity definitions should also incorporate attack location, symptoms and phase to more accurately evaluate the benefit of new treatments.