Icatibant, a New Bradykinin-Receptor Antagonist, in Hereditary Angioedema

被引：447

作者：

Cicardi, M. ^{[3
]}

Banerji, A. ^{[1
,2
]}

Bracho, F. ^{[4
]}

Malbran, A. ^{[5
]}

Rosenkranz, B.

Riedl, M. ^{[15
]}

Bork, K. ^{[6
]}

Lumry, W. ^{[16
]}

Aberer, W. ^{[17
]}

Bier, H. ^{[7
]}

Bas, M. ^{[7
]}

Greve, J. ^{[8
]}

Hoffmann, T. K. ^{[8
]}

Farkas, H. ^{[18
]}

Reshef, A. ^{[19
]}

Ritchie, B. ^{[22
]}

Yang, W. ^{[23
]}

Grabbe, J. ^{[9
]}

Kivity, S. ^{[20
]}

Kreuz, W. ^{[10
]}

Levy, R. J. ^{[26
]}

Luger, T. ^{[11
]}

Obtulowicz, K. ^{[27
]}

Schmid-Grendelmeier, P. ^{[28
]}

Bull, C. ^{[28
]}

Sitkauskiene, B. ^{[30
]}

Smith, W. B. ^{[31
]}

Toubi, E. ^{[21
]}

Werner, S. ^{[34
]}

Anne, S. ^{[36
]}

Bjorkander, J. ^{[35
]}

Bouillet, L. ^{[37
]}

Cillari, E. ^{[40
]}

Hurewitz, D. ^{[41
]}

Jacobson, K. W. ^{[42
]}

Katelaris, C. H. ^{[32
]}

Maurer, M. ^{[12
]}

Merk, H. ^{[13
]}

Bernstein, J. A. ^{[43
]}

Feighery, C. ^{[44
]}

Floccard, B. ^{[38
]}

Gleich, G. ^{[45
]}

Hebert, J. ^{[24
]}

Kaatz, M. ^{[14
]}

Keith, P. ^{[25
]}

Kirkpatrick, C. H. ^{[46
]}

Langton, D. ^{[33
]}

Martin, L. ^{[39
]}

Pichler, C. ^{[29
]}

Resnick, D. ^{[47
]}

机构：

[1] Massachusetts Gen Hosp, Boston, MA 02114 USA

[2] Harvard Univ, Sch Med, Boston, MA USA

[3] Univ Milan, Milan, Italy

[4] Georgetown Univ Hosp, Lombardi Canc Ctr, Washington, DC 20007 USA

[5] Hosp Britan Buenos Aires, Buenos Aires, DF, Argentina

[6] Johannes Gutenberg Univ Mainz, Mainz, Germany

[7] Tech Univ Munich, Munich, Germany

[8] Univ Dusseldorf, Dusseldorf, Germany

[9] Univ Hosp Lubeck, Lubeck, Germany

[10] Goethe Univ Frankfurt, Frankfurt, Germany

[11] Univ Hosp Munster, Munster, Germany

[12] Charite, D-13353 Berlin, Germany

[13] Univ Hosp Rhein Westfal Tech Hsch Aachen, Aachen, Germany

[14] Univ Jena, Jena, Germany

[15] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA

[16] Asthma Allergy Res Associates Res Ctr, Dallas, TX USA

[17] Med Univ Graz, Graz, Austria

[18] Semmelweis Univ, H-1085 Budapest, Hungary

[19] Chaim Sheba Med Ctr, IL-52621 Tel Hashomer, Israel

[20] Tel Aviv Univ, Tel Aviv Sourasky Med Ctr, IL-69978 Tel Aviv, Israel

[21] Bnai Zion Med Ctr, Haifa, Israel

[22] Univ Alberta, Edmonton, AB, Canada

[23] Allergy & Asthma Res Ctr, Ottawa, ON, Canada

[24] Ctr Rech Appl Allergie Quebec, Quebec City, PQ, Canada

[25] McMaster Univ, Hamilton Hlth Sci Ctr, Hamilton, ON, Canada

[26] Family Allergy & Asthma Ctr, Atlanta, GA USA

[27] Szpital Uniwersytecki Krakowie, Krakow, Poland

[28] Univ Zurich Hosp, CH-8091 Zurich, Switzerland

[29] Insel Spital BE Bern, Bern, Switzerland

[30] Kaunas Univ Med, Kaunas, Lithuania

[31] Royal Adelaide Hosp, Adelaide, SA 5000, Australia

[32] Westmead Hosp, Sydney, NSW, Australia

[33] Frankston Hosp, Frankston, Vic, Australia

[34] Univ Lund Hosp, S-22185 Lund, Sweden

[35] Sahlgrens Univ Hosp, Gothenburg, Sweden

[36] Asthma Allergy & Immunol Ctr, Flint, MI USA

[37] CHU Grenoble, F-38043 Grenoble, France

[38] Hop Edouard Herriot, Lyon, France

[39] Ctr Hosp Reg Orleans, Orleans, France

[40] Azienda Osped V Cervello, Palermo, Italy

[41] Allergy Clin Tulsa, Tulsa, OK USA

[42] Allergy & Asthma Res Grp, Eugene, OR USA

[43] Univ Cincinnati, Cincinnati, OH USA

[44] St James Hosp, Dublin, Ireland

[45] Univ Utah, Hlth Sci Ctr, Salt Lake City, UT USA

[46] Univ Colorado, Hlth Sci Ctr, Denver, CO USA

[47] Columbia Univ, Med Ctr, New York, NY USA

[48] Clin Res Associates Tidewater, Norfolk, VA USA

来源：

NEW ENGLAND JOURNAL OF MEDICINE | 2010年 / 363卷 / 06期

基金：

美国国家卫生研究院;

关键词：

C1 INHIBITOR CONCENTRATE; ANGIONEUROTIC EDEMA; LARYNGEAL EDEMA; TRANEXAMIC ACID;

D O I：

10.1056/NEJMoa0906393

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

BACKGROUND 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. METHODS 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. RESULTS 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. CONCLUSIONS 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.)

引用

页码：532 / 541

页数：10

共 20 条

[1] Asphyxiation by laryngeal edema in patients with hereditary angioedema [J].