Long-term prophylaxis for hereditary angioedema: Navigating the switch between therapies

Long-term prophylactic treatments (LTPs) are a major component of disease management for patients with hereditary angioedema (HAE). Patients with HAE experience considerable disease burden, as the frequent, unpredictable, and potentially life-threatening nature of HAE attacks negatively impacts patients' quality of life. LTPs aim to mitigate HAE symptoms by reducing HAE attack frequency and severity, leading to improved disease management and quality of life. As the treatment landscape has recently expanded with the addition of approved LTPs (namely, garadacimab and donidalorsen in 2025), the decision to switch between therapies is becoming increasingly common in clinical practice, and physicians and patients must carefully navigate these treatment transitions to minimize the risk of breakthrough HAE attacks and other safety concerns. Across clinical studies, treatment switching was reported for a variety of reasons, including suboptimal efficacy or frequent breakthrough attacks, safety and adverse events, family planning, treatment burden (including the LTP dosing frequency and route of administration), and drug costs and access. As these treatment options have unique mechanisms of action, durations of effect, and drug clearance rates, clinicians must carefully evaluate approaches for patients to safely switch between therapies while aiming to minimize the risk of breakthrough attacks due to lapses in prophylaxis. This review summarizes the current clinical data available in patients who have switched between first-line LTPs (namely, C1 inhibitor, lanadelumab, and berotralstat), recently approved LTPs garadacimab and donidalorsen, and second-line LTPs (androgens and antifibrinolytics) and it aims to inform health care providers as they navigate this complex treatment landscape. Clinical data available that directly evaluate or compare switching strategies between LTPs are limited, highlighting the need for further prospective studies to better characterize treatment outcomes and guide switching treatments for patients with HAE.