Ecallantide for treatment of acute hereditary angioedema attacks: Analysis of efficacy by patient characteristics
ABSTRACT Hereditary angioedema (HAE) is characterized by episodic attacks of edema. HAE is caused by low levels of the protein C1 esterase inhibitor, which inhibits plasma kallikrein, the enzyme responsible for converting high-molecular-weight kininogen to bradykinin. Unregulated production of bradykinin leads to the characteristic clinical symptoms of swelling and pain. Ecallantide is a novel plasma kallikrein inhibitor effective for treatment of acute HAE attacks. This study was designed to analyze the efficacy of ecallantide for treating HAE attacks by attack location, attack severity, patient gender, and body mass index (BMI). An analysis of integrated data from two double-blind, placebo-controlled trials of ecallantide for treatment of acute HAE attacks was undertaken. For the purpose of analysis, symptoms were classified by anatomic location and, for each location, by the patient-assessed severity of the attack. Efficacy versus placebo was examined using two validated patient-reported outcomes: treatment outcome score and mean symptom complex severity score. One hundred forty-three attacks were analyzed (73 ecallantide and 70 placebo). Ecallantide was equally effective in both male and female subjects. Ecallantide had decreased efficacy for patients with BMI > 30 kg/m(2). Ecallantide showed efficacy for treatment of severe and moderate attacks, and was effective for abdominal, internal head and neck, external head and neck, and cutaneous locations. In summary, ecallantide is effective for treatment of acute HAE attacks of different symptom locations and severity; outcomes were similar for men and women. However, the standard dose was less effective for obese patients.
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ABSTRACT: Hereditary angioedema (HAE) is a rare autosomal dominant disease caused by deficient or dysfunctional C1 inhibitor (C1 INH). HAE patients experience recurrent episodes of angioedema affecting the extremities, face, genitalia or submucosal edema in the abdomen or upper airway. Laryngeal attacks can be fatal. The determination of optimal therapy should be based on individualization of patient history and preferences. The parameters include attack frequency, location, severity and burden of illness on quality of life. Patients with HAE need medications for acute attacks; some also require prophylaxis. This is an overview of HAE treatments currently available in the US and how to individualize therapy for patients based on their circumstances. A literature search was performed for HAE and therapeutic modalities currently available. HAE guidelines and randomized, controlled clinical trials were evaluated. There are several options for acute and prophylactic treatment of HAE that have been approved by the Food and Drug Administration. Acute treatments include C1 INH, a replacement therapy; ecallantide, a kallikrein inhibitor; and icatibant, a bradykinin-2 receptor antagonist. Prophylactic treatments include attenuated androgens and C1 INH. These options have been proven safe and effective in clinical trials. Optimal therapy is based on the individual patients need regarding on-demand therapy and/or prophylactic therapy, short-term or long-term. Patients with HAE have individual requirements, based on the nature and frequency of past attacks, occupation, proximity to trained medical personnel, and patient preference. These factors should be used to create a patient-centered approach to management of HAE.Allergy and Asthma Proceedings 01/2013; 34(1):7-12. DOI:10.2500/aap.2013.34.3624 · 3.35 Impact Factor
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ABSTRACT: Introduction: Hereditary angioedema (HAE) is a rare disorder with recurring edema formation in the subcutis and the submucosa. The growing understanding of its pathophysiology yielded a number of new orphan drugs with diverse targets and delivery routes. Because HAE is bradykinin-mediated, its pharmacotherapy focuses on inhibiting the release, or the receptor action, of this vasoactive peptide. Areas covered: This summary is intended as a brief review of the disease and of the medicinal products (non-pathogenic and pathogenic medications) available for its therapy. It also attempts to outline the choices in its complex management, and to assist in delivering appropriate care with minimum delay. The primary objective of therapy is to prevent edema, as well as to relieve its symptoms. Nowadays, many innovative drugs are available; their efficacy and safety have been demonstrated in controlled clinical trials. C1-inhibitor concentrates, prepared from human plasma, or produced by recombinant technology, are used for supplementation. Kallikrein inhibitors block the release of bradykinin, whereas icatibant interferes with its binding to the bradykinin B2 receptor. Expert opinion: The expansion of therapeutic alternatives allows individualized treatment supported by recent international guidelines and recommendations.01/2013; 1(2). DOI:10.1517/21678707.2013.761568
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ABSTRACT: Each year there are a substantial number of emergency department (ED) visits for angioedema and allergic reactions in the United States. Angioedema is commonly mistaken for an allergic reaction, possibly affecting the treatment rendered. We sought to determine the characteristics of U.S. ED visits for acute angioedema and to determine their differences from visits for allergic reactions. We used 2001-2009 data from the National Hospital Ambulatory Medical Care Survey. Using ED diagnoses (defined by the International Classification of Diseases, 9th Revision codes), we identified visits involving angioedema (ICD-9 277.6 and 995.1) or allergic reaction (ICD-9 995.6, 995.0, 995.4, 995.3, and 708). Accounting for the weighted sampling design, we determined the annual number of angioedema and allergic reaction cases, the characteristics of the affected patients, course of care, and patient outcomes. During 2001-2009 there were 1.05 billion ED visits, including 979,342 for angioedema and 8,814,601 for allergic reactions. These figures corresponded to 108,816 (95% CI, 82,246-132,386) annual visits for angioedema and 979,400 (CI, 874,562-1,084,238) annual visits for allergic reactions. Angioedema patients spent >3 hours in the ED and 11% were admitted to the hospital. Steroids and antihistamines were the most common treatments rendered for both angioedema and allergic reaction patients. There are >100,000 annual visits for angioedema in the United States, with key differences and similarities between allergic reaction and angioedema cases. These findings underscore the large number of angioedema cases presenting to U.S. EDs and the opportunities for novel angioedema therapy use in this setting.Allergy and Asthma Proceedings 03/2013; 34(2):150-4. DOI:10.2500/aap.2013.34.3640 · 3.35 Impact Factor