Abstract

Hereditary angioedema (HAE) is a rare genetic disorder characterized by unpredictable swelling attacks due to bradykinin. In recent years, the therapeutic landscape has evolved significantly with the introduction of targeted therapies, necessitating a comprehensive review of their efficacy and safety. Following PRISMA 2020 guidelines, a systematic review of randomized controlled trials (RCTs) was conducted from 2014 to 2025, sourced from PubMed, Scopus, Medline, and Web of Science. The search focused on HAE therapies, including C1-esterase inhibitors, bradykinin B2 receptor antagonists, and kallikrein inhibitors. Outcomes included attack frequency, time to relief, quality of life (QoL), and adverse events (AEs). Five Phase III RCTs were included. Prophylactic treatments [berotralstat, subcutaneous C1-esterase inhibitor (C1-INH), lanadelumab] achieved attack rate reductions of 84.8%-95%, with monthly attack rates of ≤0.53. Significant improvements in QoL metrics (AE-QoL, TSQM, EQ-5D) were observed. AEs were primarily mild to moderate (e.g., nasopharyngitis, injection-site reactions). For acute treatment, recombinant human C1-INH provided significantly faster symptom relief (median 90 minutes) compared to placebo (152 minutes). Contemporary HAE therapies demonstrated high efficacy and acceptable safety profiles for both prophylaxis and acute treatment. Treatment choice should be individualized, with injectable therapies offering optimal control and oral options providing a needle-free alternative. Future research should prioritize head-to-head comparisons and long-term realworld evidence.

Key words: Efficacy, safety, hereditary angioedema, therapeutic strategies, systematic review.