Treatment of acute edema attacks in hereditary angioedema with a bradykinin receptor-2 antagonist (Icatibant)

Background: In hereditary angioedema, bradykinin is assumed to be the most important mediator of edema formation. Objective: To assess whether the selective bradykinin receptor-2 antagonist Icatibant is effective in acute edema attacks of hereditary angioedema. Methods: In this uncontrolled pilot study, 15 patients with 20 attacks were treated with Icatibant. The attacks were analyzed by using a standardized and validated visual analog scale measurement and compared with historical data of untreated attacks. Plasma bradykinin concentration was measured before and 4 hours after intravenous Icatibant treatment. Results: Symptom intensity decreased within 4 hours after administration of Icatibant; the median time to onset of symptom relief was 1.50,1.42, and 1.13 hours in the intravenous groups and 0.58 and 0.45 hours in the subcutaneous groups, respectively. The median difference in the 10-cm visual analog scale 4 hours after start of treatment was 4.11 cm (95% CI, 1.72-6.07). Compared with untreated attacks, Icatibant treatment reduced the mean (SD) time to onset of symptom relief by 97% from 42 +/- 14 to 1.16 +/- 0.95 hours (all groups combined). Median bradykinin concentration was 7-fold above the norm during acute attacks at 48.5 pmol/L and decreased to 18.0 pmol/L 4 hours after Icatibant infusion or injection. Conclusion: Icatibant was effective in treating acute attacks of hereditary angioedema. Clinical implications: This is the first report demonstrating the clinical usefulness of antagonizing bradykinin binding to bradykinin receptor-2 in hereditary angioedema.