Response to ecallantide treatment of acute attacks of hereditary angioedema based on time to intervention: results from the EDEMA clinical trials.

Abstract

Hereditary Angioedema (HAE) is a rare, debilitating, genetic disorder characterized by acute attacks of edema without urticaria. Ecallantide, a direct plasma kallikrein inhibitor, is approved for treatment of acute HAE attacks. This article addresses the efficacy of ecallantide in the treatment of moderate-to-severe attacks of HAE based on time to treatment. A post hoc integrated analysis of the EDEMA4 and EDEMA3-DB clinical trials was performed based on the time to patient's treatment, defined as the time from initial recognition of moderate-to-severe symptoms to dosing (cohort, 0-2, >2-4, >4-6, >6-8, and >8 hours). Mean symptom complex severity (MSCS) score and treatment outcome score (TOS) were analyzed. Complete or near-complete resolution of symptoms was assessed at 4 and 24 hours. In this analysis, 70 patients received 30 mg of subcutaneous (s.c.) ecallantide and 73 patients received placebo. Change from baseline in MSCS score and TOS at 4 hours revealed significantly better response to ecallantide versus placebo for patients treated >2-4 (n = 46; p = 0.002; p = 0.003) or >4-6 (n = 47; p = 0.044; p = 0.043) hours after symptom onset. Fewer patients were treated within 2 hours of symptom onset; for these patients (n = 10; p = 0.752; p = 0.422) treatment did not achieve statistical significance. For overall response, complete or near-complete resolution was greatest within the 0- to 2-hour cohort (71.4%). As with other therapies for HAE early ecallantide therapy is optimal. Treatment with ecallantide within 6 hours of symptom onset leads to more rapid and sustained improvement of symptoms.

• Authors: Erin Banta, Patrick Horn, Timothy J Craig
• Journal: Allergy and asthma proceedings (Allergy Asthma Proc) 2011 Jul-Aug Vol. 32 Issue 4 Pg. 319-24 ISSN: 1539-6304 [Electronic] United States
• PMID: 21781409 (Publication Type: Clinical Trial, Phase III, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Enzyme Inhibitors
• Peptides
• ecallantide
• Kallikreins

Topics

• Acute Disease
• Adolescent
• Adult
• Aged
• Angioedemas, Hereditary (drug therapy, physiopathology)
• Child
• Double-Blind Method
• Enzyme Inhibitors (administration & dosage, therapeutic use)
• Female
• Humans
• Kallikreins (antagonists & inhibitors)
• Male
• Middle Aged
• Peptides (administration & dosage, therapeutic use)
• Time Factors
• Treatment Outcome
• Young Adult