164 Treatment of Acquired Angioedema with the Bradykinin Receptor Antagonist Icatibant

BACKGROUND: Complement-mediated acquired angioedema (AAE) is a rare condition characterized by an increased degradation of C1-esterase inhibitor (C1-INH) associated with lymphoproliferative disorders (AAE type I) or caused by autoantibodies against C1-INH (AAE type II). Reduced C1-INH activity leads to uncontrolled bradykinin formation and to angioedema symptoms. There is no established treatment for AAE. Replacement with plasma-derived C1-INH is effective in most patients with life-threatening attack; however, icatibant, a bradykinin B2 receptor antagonist, may represent an alternative treatment. METHODS: We describe 2 patients with AAE who were treated with icatibant during acute attacks. Patient 1 is an 86 year old male who reported cutaneous and abdominal attacks of angioedema beginning 2 years earlier with a frequency of 2 to 3 month. He had low C1-INH (antigenic and functional) C4 levels, normal C1q levels and detectable of anti-C1-INH IgM and anti-C1q IgA. Because of increased frequency, his attacks were treated with icatibant (30 mg s.c.). Patient 2 is a 64 year old female who reported angioedema of the tongue and upper limbs in the last 4 years. Her C4, C1-INH and C1q were low. Monoclonal gammopathy (6%) and IgA anti C1-INH were found. After the diagnosis she started icatibant for acute attacks. RESULTS: The first patient used icatibant consecutively for 20 attacks (mainly abdominal), with rapid resolutions of symptoms and no adverse events. Symptoms resolution began 30 minutes after administration of icatibant and resolution was complete in 3 to 4 hours. The second patient used icatibant for a tongue attack, a mixed cutaneous-tongue attack and a severe facial attack, with first symptom improvement in 25 minutes and complete resolution after 16 to 18 hours. The only adverse event was erythema at the injection site lasting few minutes. CONCLUSIONS: Icatibant is an effective and well tolerated treatment of acute attacks in patients with AAE. Our data suggest that blocking bradykinin activity could be considered a good therapeutic strategy particularly in patients with anti-C1-INH antibodies.