Long-Term Outcomes with Subcutaneous C1-Inhibitor Replacement Therapy for Prevention of Hereditary Angioedema Attacks

被引：66

作者：

Craig, Timothy ^{[1
]}

Zuraw, Bruce ^{[2
,3
]}

Longhurst, Hilary ^{[4
]}

Cicardi, Marco ^{[5
]}

Bork, Konrad ^{[6
]}

Grattan, Clive ^{[7
]}

Katelaris, Constance ^{[8
]}

Sussman, Gordon ^{[9
]}

Keith, Paul K. ^{[10
]}

Yang, William ^{[11
]}

Hebert, Jacques ^{[12
]}

Hanzlikova, Jana ^{[13
,14
]}

Staubach-Renz, Petra ^{[15
]}

Martinez-Saguer, Inmaculada ^{[16
]}

Magerl, Markus ^{[17
]}

Aygoren-Pursun, Emel ^{[18
]}

Farkas, Henriette ^{[19
]}

Reshef, Avner ^{[20
]}

Kivity, Shmuel ^{[21
]}

Neri, Sergio ^{[22
]}

Crisan, Ioana ^{[23
]}

Caballero, Teresa ^{[24
]}

Baeza, Maria L. ^{[25
]}

Dolores Hernandez, Maria ^{[26
]}

Li, Henry ^{[27
]}

Lumry, William ^{[28
]}

Bernstein, Jonathan A. ^{[29
]}

Hussain, Iftikar ^{[30
]}

Anderson, John ^{[31
]}

Schwartz, Lawrence B. ^{[32
]}

Jacobs, Joshua ^{[33
]}

Manning, Michael ^{[34
]}

Levy, Donald ^{[35
]}

Riedl, Marc ^{[36
]}

Christiansen, Sandra ^{[36
]}

Feuersenger, Henrike ^{[37
]}

Pragst, Ingo ^{[37
]}

Mycroft, Sarah ^{[38
]}

Pawaskar, Dipti ^{[38
]}

Jacobs, Iris ^{[38
]}

Zuraw, Bruce L.

Cicardi, Marco ^{[5
]}

Craig, Timothy ^{[1
]}

Longhurst, Hilary ^{[4
]}

Grattan, Clive ^{[7
]}

Bork, Konrad ^{[6
]}

Kreuz, Wolfhart

Jacobs, Iris ^{[38
]}

Pragst, Ingo ^{[37
]}

机构：

[1] Penn State Univ, Dept Med Pediat & Grad Studies, Hershey Med Ctr, Hershey, PA USA

[2] Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA

[3] San Diego VA Healthcare, La Jolla, CA USA

[4] Royal London Hosp, Barts Hlth NHS Trust, Immunol Dept, London, England

[5] L Sacco Univ Milan, ASST Fatebenefratelli Sacco, Dept Biomed & Clin Sci, Milan, Italy

[6] Johannes Gutenberg Univ Mainz, Dept Dermatol, Mainz, Germany

[7] Tower Wing Guys Hosp, St Johns Inst Dermatol, London, England

[8] Campbelltown Hosp, Dept Med Immunol & Allergy, Campbelltown, NSW, Australia

[9] Gordon Sussman Clin Res Inc, Toronto, ON, Canada

[10] McMaster Univ, Med Ctr Site, Hamilton, ON, Canada

[11] Ottawa Allergy Res Corp, Ottawa, ON, Canada

[12] CSAC, Quebec City, PQ, Canada

[13] Fakultni Nemocnice Plzen, Plzen, Czech Republic

[14] Ustav Imunol & Alergol, Plzen, Czech Republic

[15] Univ Klin Mainz, Hautklin & Poliklin, Clin Res Ctr, Mainz, Germany

[16] HZRM Haemophilia Ctr Rhein Main, Morfelden Walldorf, Germany

[17] Charite Univ Med Berlin, Dept Dermatol & Allergy, Berlin, Germany

[18] Klinikum Johann Wolfgang Goethe Univ, Klin Kinder & Jugendmed, Frankfurt, Germany

[19] Semmelweis Univ, Dept Internal Med 3, Hungarian Angioedema Reference Ctr, Budapest, Hungary

[20] Barzilai Univ, Med Ctr Allergy Immunol & Angioedema, Ashqelon, Israel

[21] Tel Aviv Sourasky Med Ctr, Allergy & Immunol Unit, Tel Aviv, Israel

[22] Azienda Osped Univ Policlin Vittorio Emanuele, Dipartimento Med Interna, Catania, Italy

[23] Spitalul Clin Municipal Cluj, Cluj Napoca, Romania

[24] Ctr Invest Biomed Red Enfermedades Raras CIBERER, La Paz Inst Hlth Res IdiPaz, Serv Alergia, U754, Madrid, Spain

[25] Hosp Gen Univ Gregorio Maranon, Ctr Invest Biomed Red Enfermedades Raras CIBERER, Inst Invest Gregorio Maranon, Serv Alergol,U761, Madrid, Spain

[26] Hosp Univ La Fe, Serv Alergia, Valencia, Spain

[27] Inst Asthma & Allergy, Chevy Chase, MD USA

[28] AARA Res Ctr, Dallas, TX USA

[29] Bernstein Clin Res Ctr LLC, Cincinnati, OH USA

[30] Asthma & Immunol Ctr, Allergy, Tulsa, OK USA

[31] Clin Res Ctr Alabama, Alabama Allergy & Asthma, Birmingham, AL USA

[32] Virginia Commonwealth Univ, Dept Internal Med, Richmond, CA USA

[33] Allergy & Asthma Clin Res, Walnut Creek, CA USA

[34] Med Res Arizona, Scottsdale, AZ USA

[35] Dr Donald Levy MD, Orange, CA USA

[36] Univ Calif San Diego, Sch Med, Clin Allergy & Immunol Sect, La Jolla, CA 92093 USA

[37] CSL Behring, Marburg, Germany

[38] CSL Behring LLC, King Of Prussia, PA USA

来源：

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY-IN PRACTICE | 2019年 / 7卷 / 06期

关键词：

C1-esterase inhibitor; HAEGARDA; Hereditary angioedema; Subcutaneous; Long-term; Prophylaxis; Safety; C1 INHIBITOR DEFICIENCY; PATHOPHYSIOLOGY; PROPHYLAXIS; MANAGEMENT; DIAGNOSIS; CONSENSUS;

D O I：

10.1016/j.jaip.2019.01.054

中图分类号：

R392 [医学免疫学];

学科分类号：

100102 ;

摘要：

BACKGROUND: For the prevention of attacks of hereditary angioedema (HAE), the efficacy and safety of subcutaneous human C1-esterase inhibitor (C1-INH [SC]; HAEGARDA, CSL Behring) was established in the 16-week Clinical Study for Optimal Management of Preventing Angioedema with Low-Volume Subcutaneous C1-Inhibitor Replacement Therapy (COMPACT). OBJECTIVE: To assess the long-term safety, occurrence of angioedema attacks, and use of rescue medication with C1-INH(SC). METHODS: Open-label, randomized, parallel-arm extension of COMPACT across 11 countries. Patients with frequent angioedema attacks, either study treatment-naive or who had completed COMPACT, were randomly assigned (1:1) to 40 IU/ kg or 60 IU/kg C1-INH(SC) twice per week, with conditional uptitration to optimize prophylaxis (ClinicalTrials.gov registration no. NCT02316353). RESULTS: A total of 126 patients with a monthly attack rate of 4.3 in 3 months before entry in COMPACT were enrolled and treated for a mean of 1.5 years; 44 patients (34.9%) had more than 2 years of exposure. Mean steady-state C1-INH functional activity increased to 66.6% with 60 IU/kg. Incidence of adverse events was low and similar in both dose groups (11.3 and 8.5 events per patient-year for 40 IU/kg and 60 IU/kg, respectively). For 40 IU/kg and 60 IU/kg, median annualized attack rates were 1.3 and 1.0, respectively, and median rescue medication use was 0.2 and 0.0 times per year, respectively. Of 23 patients receiving 60 IU/kg for more than 2 years, 19 (83%) were attack-free during months 25 to 30 of treatment. CONCLUSIONS: In patients with frequent HAE attacks, long-term replacement therapy with C1-INH(SC) is safe and exhibits a substantial and sustained prophylactic effect, with the vast majority of patients becoming free from debilitating disease symptoms. (C) 2019 The Authors. Published by Elsevier Inc. on behalf of the American Academy of Allergy, Asthma & Immunology.

引用

页码：1793 / +

页数：12

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