Real-World Evidence on the Management of Hereditary Angioedema With Normal C1 Inhibitor

Area of Science:

• Immunology
• Genetics
• Pharmacology

Background:

• Hereditary angioedema with normal C1 inhibitor (HAE-nC1INH) presents diagnostic challenges and lacks evidence-based guidelines.
• This bradykinin-mediated disorder is rare and heterogeneous, requiring subtype-oriented management.

Purpose of the Study:

• To characterize clinical features and therapeutic strategies in Brazilian HAE-nC1INH patients.
• To support individualized management based on specific HAE-nC1INH subtypes.

Main Methods:

• A multicenter, cross-sectional study involving the Brazilian Group for the Study of Hereditary Angioedema (GEBRAEH).
• Data collected via a standardized online questionnaire in December 2024.
• Descriptive and inferential statistical analyses were performed.

Main Results:

• 116 symptomatic patients were analyzed: 92 with Factor XII mutation, 21 with unknown genetic cause, and 3 with Angiopoietin-1 mutation.
• Combined estrogen-progestin oral contraceptive (COC) withdrawal, alone or with progestins, was the primary intervention, showing high efficacy (up to 100%) in HAE with Factor XII mutation.
• COC withdrawal significantly reduced attack frequency and duration; lanadelumab showed efficacy in other subtypes. Four patients experienced late relapses.

Conclusions:

• Combined estrogen-progestin oral contraceptive withdrawal is the most effective first-line treatment for HAE with Factor XII mutation, enhanced by progestins.
• Tranexamic acid and lanadelumab offer complementary options for selected patients.
• Long-term monitoring is essential, particularly during hormonal fluctuations, due to the risk of late relapses.