D2.348 - Clinical Course of Hereditary Angioedema Patients Transitioning off Androgens

Historically, androgen therapy has been a cornerstone in the prophylactic treatment of hereditary angioedema (HAE). However, androgen therapy is associated with significant adverse effects, such as hepatic dysfunction, increased cardiovascular risk, and endocrine disruption, which has prompted the need for targeted therapies including novel kallikrein inhibitors such as lanadelumab and berotralstat. Our objective is to evaluate clinical outcomes in HAE patients transitioned from androgen therapy to targeted prophylactic agents.

We conducted a retrospective, observational audit of HAE patients managed at Barts Health NHS Trust, London, UK - a referral centre of excellence. The study included patients who were transitioned from androgen therapy between 2007 and 2024. We collected data on patient demographics, disease severity (frequency and severity of attacks), and patient-reported outcomes before and after transitioning to targeted therapies.

In the initial analysis, a total of 6 patients (1 female, 5 male; median age 34 years, range 23-46 years) were included. All patients were transitioned to berotralstat, with 3 later switching to lanadelumab due to inadequate control with berotralstat. In 3 cases, the transition was driven by ineffectiveness of androgens in controlling attack frequency; the other 3 transitioned due to concerns over long-term androgen side effects, despite adequate disease control. Half of the transitions were sudden, while the remainder were gradual. In 2 cases, androgens were weaned off with an overlap period with berotralstat, during which attack frequency increased in one of the cases. In another case, androgen weaning occurred without overlap, and in three cases with sudden cessation, there was a period without prophylaxis, resulting in increased attack frequency. One patient reverted to androgen therapy due to uncontrolled HAE on berotralstat.

The transition of HAE patients from androgens to targeted prophylactic therapies currently lacks standardized protocols as exemplified in our cohort. Establishing guidelines could be beneficial for clinicians to ensure safe and effective transitions in HAE management and minimisation of disease burden on patients.