Paula Busse, Andrea Zanichelli, Jonathan A Bernstein, John Anderson, Stephen Betschel, Daniel N Castaner, Matthew Otule, Tara Piccolo, William R Lumry
Hereditary angioedema (HAE) is a rare genetic disease characterized by unpredictable, painful cutaneous and/or subcutaneous swelling attacks; laryngeal attacks can be fatal. For many patients, long-term prophylaxis (LTP) is critical for disease control and quality of life.Lanadelumab, a plasma kallikrein inhibitor, was approved for HAE LTP for adults and adolescents in 2018 and for children aged ≥ 2 years in 2023; it is currently one of the guideline-recommended, first-line LTP options. By integrating 7 years of cumulative clinical trial and real-world data, this narrative review summarizes lanadelumab long-term effectiveness and safety in adult, adolescent, and pediatric HAE populations. Outcomes in 41 peer-reviewed publications were evaluated, including 5 clinical trials involving 262 lanadelumab-treated patients and 28 real-world studies comprising ~ 700 patients. Across clinical trials, lanadelumab reduced attack rates by up to 100%, with an average of 24.9-27.3 patient-reported attack-free days per 28-day period. These findings were largely corroborated by real-world data, including 2 large observational studies with > 100 patients each. Patient-reported disease control and health-related quality of life improved consistently across both settings. The main treatment-related adverse events across studies were injection site reactions. Treatment persistence was generally high in clinical practice. Unmet needs remain for specific populations, including pregnant or lactating patients and those without access to guideline-recommended LTP. Future research should address real-world outcomes in pediatric patients, extended dosing intervals in well-controlled disease, transitions from other LTP therapies, and cost-effectiveness. Overall, sustained effectiveness, safety, and quality-of-life benefits of lanadelumab reinforce its role as a cornerstone of HAE management.