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Icatibant, a new bradykinin-receptor antagonist, in hereditary angioedema.

ABSTRACT: Hereditary angioedema is characterized by recurrent attacks of angioedema of the skin, larynx, and gastrointestinal tract. Bradykinin is the key mediator of symptoms. Icatibant is a selective bradykinin B2 receptor antagonist.In two double-blind, randomized, multicenter trials, we evaluated the effect of icatibant in patients with hereditary angioedema presenting with cutaneous or abdominal attacks. In the For Angioedema Subcutaneous Treatment (FAST) 1 trial, patients received either icatibant or placebo; in FAST-2, patients received either icatibant or oral tranexamic acid, at a dose of 3 g daily for 2 days. Icatibant was given once, subcutaneously, at a dose of 30 mg. The primary end point was the median time to clinically significant relief of symptoms.A total of 56 and 74 patients underwent randomization in the FAST-1 and FAST-2 trials, respectively. The primary end point was reached in 2.5 hours with icatibant versus 4.6 hours with placebo in the FAST-1 trial (P=0.14) and in 2.0 hours with icatibant versus 12.0 hours with tranexamic acid in the FAST-2 trial (P<0.001). In the FAST-1 study, 3 recipients of icatibant and 13 recipients of placebo needed treatment with rescue medication. The median time to first improvement of symptoms, as assessed by patients and by investigators, was significantly shorter with icatibant in both trials. No icatibant-related serious adverse events were reported.In patients with hereditary angioedema having acute attacks, we found a significant benefit of icatibant as compared with tranexamic acid in one trial and a nonsignificant benefit of icatibant as compared with placebo in the other trial with regard to the primary end point. The early use of rescue medication may have obscured the benefit of icatibant in the placebo trial. (Funded by Jerini; ClinicalTrials.gov numbers, NCT00097695 and NCT00500656.)

SUBMITTER: Cicardi M

PROVIDER: S-EPMC4662377 | biostudies-literature | 2010 Aug

REPOSITORIES: biostudies-literature

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Icatibant, a new bradykinin-receptor antagonist, in hereditary angioedema.

Cicardi Marco M Banerji Aleena A Bracho Francisco F Malbrán Alejandro A Rosenkranz Bernd B Riedl Marc M Bork Konrad K Lumry William W Aberer Werner W Bier Henning H Bas Murat M Greve Jens J Hoffmann Thomas K TK Farkas Henriette H Reshef Avner A Ritchie Bruce B Yang William W Grabbe Jürgen J Kivity Shmuel S Kreuz Wolfhart W Levy Robyn J RJ Luger Thomas T Obtulowicz Krystyna K Schmid-Grendelmeier Peter P Bull Christian C Sitkauskiene Brigita B Smith William B WB Smith William B WB Toubi Elias E Werner Sonja S Anné Suresh S Björkander Janne J Bouillet Laurence L Cillari Enrico E Hurewitz David D Jacobson Kraig W KW Katelaris Constance H CH Maurer Marcus M Merk Hans H Bernstein Jonathan A JA Feighery Conleth C Floccard Bernard B Gleich Gerald G Hébert Jacques J Kaatz Martin M Keith Paul P Kirkpatrick Charles H CH Langton David D Martin Ludovic L Pichler Christiane C Resnick David D Wombolt Duane D Fernández Romero Diego S DS Zanichelli Andrea A Arcoleo Francesco F Knolle Jochen J Kravec Irina I Dong Liying L Zimmermann Jens J Rosen Kimberly K Fan Wing-Tze WT

The New England journal of medicine 20100801 6

<h4>Background</h4>Hereditary angioedema is characterized by recurrent attacks of angioedema of the skin, larynx, and gastrointestinal tract. Bradykinin is the key mediator of symptoms. Icatibant is a selective bradykinin B2 receptor antagonist.<h4>Methods</h4>In two double-blind, randomized, multicenter trials, we evaluated the effect of icatibant in patients with hereditary angioedema presenting with cutaneous or abdominal attacks. In the For Angioedema Subcutaneous Treatment (FAST) 1 trial, p ...[more]

PMID: 20818888

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Project description:Hereditary angioedema (HAE) is an autosomal dominant, potentially life-threatening condition, manifesting as recurrent and self-limiting episodes of facial, laryngeal, genital, or peripheral swelling with abdominal pain secondary to intra-abdominal edema. The estimated prevalence of HAE in the general population is one individual per 50,000, with reported ranges from 1:10,000 to 1:150,000, without major sex or ethnic differences. Various treatment options for acute attacks and prophylaxis of HAE are authorized and available in the market, including plasma-derived (Berinert®, Cinryze®, and Cetor®) and recombinant (Rhucin® and Ruconest™) C1 inhibitors, kallikrein inhibitor-ecallantide (Kalbitor®), and bradykinin B2 receptor antagonist-icatibant (Firazyr®). Some of these drugs are used only to treat HAE attacks, whereas others are only approved for prophylactic therapies and all of them have improved disease outcomes due to their different mechanisms of action. Bradykinin and its binding to B2 receptor have been demonstrated to be responsible for most of the symptoms of HAE. Thus icatibant (Firazyr®), a bradykinin B2 receptor antagonist, has proven to be an effective and more targeted treatment option and has been approved for the treatment of acute attacks of HAE. Rapid and stable relief from symptoms of cutaneous, abdominal, or laryngeal HAE attacks has been demonstrated by 30 mg of icatibant in Phase III clinical trials. Self-resolving mild to moderate local site reactions after subcutaneous injection of icatibant were observed. Icatibant is a new, safe, and effective treatment for acute attacks of HAE. HAE has been reported to result in enormous humanistic burden to patients, affecting both physical and mental health, with a negative impact on education, career, and work productivity, and with substantial economic burdens. The timely and proper use of disease-specific treatments could improve patients' quality of life, reduce the disease-specific morbidity and mortality, and, last but not least, reduce costs associated with hospitalizations and emergency room visits. Therefore, the paradigm of HAE treatment has the potential to evolve significantly, thereby exponentially improving a patient's quality of life.

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Icatibant, a new bradykinin-receptor antagonist, in hereditary angioedema.

Publications

Icatibant, a new bradykinin-receptor antagonist, in hereditary angioedema.

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