Delphi Consensus on Attenuated Androgen Use for Long-Term Prophylaxis in Hereditary Angioedema: AURA Project.

BACKGROUND: Danazol and other attenuated androgens (AAs) have been a cornerstone of Hereditary Angioedema (HAE) long-term prophylaxis (LTP) for decades, alongside intravenous plasma-derived C1INH (pdC1INH). Danazol's potential androgenic effects, however, present several limitations to its prescription and use. With the emergence of safer and more effective LTP drugs, guidelines are now shifting danazol to a second-line option. These changes in HAE therapy require a new framework to guide physicians in the appropriate use of danazol in HAE LTP. METHODS: This study aimed to develop a consensus on key aspects of danazol management, including discontinuation strategies, through a 2-round Delphi methodology. Statements were defined by a steering committee of both Endocrinology and Allergy and Clinical Immunology specialists, considering the available evidence. A panel of 23 experts in HAE management voted on the statements to reach a consensus. RESULTS: This process resulted in 46 recommendations for the prescription, monitoring, and discontinuation of danazol in LTP, proposing specific strategies for appropriate danazol use. A consensus was achieved on contraindications for danazol usage in LTP, detailed parameters for ongoing monitoring, and instructions for therapy adjustment considering treatment effect and using patient-reported outcomes. Furthermore, seven recommendations provide guidance on the increasingly relevant challenge of danazol discontinuation in HAE patients. CONCLUSION: This Delphi study specifically addresses the gap in clinical guidance for danazol management in HAE patients. The resulting consensus document provides a valuable tool to aid the standardization of danazol discontinuation protocols and ensures that patients can access the safest and most effective treatment options available.