Timothy Craig1, Bruce Zuraw2, Hilary Longhurst3, Marco Cicardi4, Konrad Bork5, Clive Grattan6, Constance Katelaris7, Gordon Sussman8, Paul K Keith9, William Yang10, Jacques Hébert11, Jana Hanzlikova12, Petra Staubach-Renz13, Inmaculada Martinez-Saguer14, Markus Magerl15, Emel Aygören-Pürsün16, Henriette Farkas17, Avner Reshef18, Shmuel Kivity19, Sergio Neri20, Ioana Crisan21, Teresa Caballero22, Maria L Baeza23, Maria Dolores Hernandez24, Henry Li25, William Lumry26, Jonathan A Bernstein27, Iftikar Hussain28, John Anderson29, Lawrence B Schwartz30, Joshua Jacobs31, Michael Manning32, Donald Levy33, Marc Riedl34, Sandra Christiansen34, Henrike Feuersenger35, Ingo Pragst35, Sarah Mycroft36, Dipti Pawaskar36, Iris Jacobs36. 1. Department of Medicine, Pediatrics and Graduate Studies, Penn State University Hershey Medical Center, Hershey, Pa. Electronic address: tcraig@psu.edu. 2. Department of Medicine, University of California San Diego and San Diego VA Healthcare, La Jolla, Calif. 3. Immunology Department, Barts Health NHS Trust, The Royal London Hospital, London, United Kingdom. 4. Department of Biomedical and Clinical Sciences, "L. Sacco" University of Milan/ASST Fatebenefratelli-Sacco, Milan, Italy. 5. Department of Dermatology, Johannes Gutenberg University, Mainz, Germany. 6. St John's Institute of Dermatology, Tower Wing Guy's Hospital, London, United Kingdom. 7. Department of Medicine, Immunology and Allergy, Campbelltown Hospital, Campbelltown, NSW, Australia. 8. Gordon Sussman Clinical Research, Inc, Toronto, ON, Canada. 9. McMaster University Medical Center Site, Hamilton, ON, Canada. 10. Ottawa Allergy Research Corp, Ottawa, ON, Canada. 11. Clinique Specialisée en Allergie de la Capitale (CSAC), Québec, QC, Canada. 12. Fakultni nemocnice Plzen - Ustav Imunologie a Alergologie, Plzen, Czech Republic. 13. Clinical Research Centre, Hautklinik und Poliklinik der Universitätsklinik Mainz, Mainz, Germany. 14. HZRM Haemophilia Center Rhein Main, Moerfelden-Walldorf, Germany. 15. Department of Dermatology and Allergy, Charité - Universitätsmedizin Berlin, Berlin, Germany. 16. Klinikum der Johann Wolfgang-Goethe Universität, Klinik für Kinder- und Jugendmedizin, Frankfurt, Germany. 17. Hungarian Angioedema Reference Center, 3rd Department of Internal Medicine, Semmelweis University, Budapest, Hungary. 18. Barzilai University Medical Center, Allergy, Immunology & Angioedema, Ashkelon, Israel. 19. Tel Aviv Sourasky Medical Center, Allergy and Immunology Unit, Tel Aviv, Israel. 20. Dipartimento di Medicina Interna, Azienda Ospedaliero - Universitaria "Policlinico - Vittorio Emanuele," Catania, Italy. 21. Spitalul Clinic Municipal Cluj, Cluj Napoca, Romania. 22. Servicio de Alergia, Hospital, La Paz Institute for Health Research (IdiPaz), Centro de Investigacion Biomédica en Red de Enfermedades Raras (CIBERER)-U754, Madrid, Spain. 23. Hospital General Universitario Gregorio Marañón, Servicio de Alergología, Instituto de Investigación Gregorio Marañón, Centro de Investigacion Biomédica en Red de Enfermedades Raras (CIBERER)-U761, Madrid, Spain. 24. Hospital Universitario La Fe, Servicio de Alergia, Bulevar del Sur, Valencia, Spain. 25. Institute for Asthma and Allergy, Chevy Chase, Md. 26. AARA Research Center, Dallas, Texas. 27. Bernstein Clinical Research Center LLC, Cincinnati, Ohio. 28. Allergy, Asthma and Immunology Center, Tulsa, Okla. 29. Clinical Research Center of Alabama, Alabama Allergy & Asthma, Birmingham, Ala. 30. Department of Internal Medicine, Virginia Commonwealth University, Richmond, Va. 31. Allergy & Asthma Clinical Research, Walnut Creek, Calif. 32. Medical Research of Arizona, Scottsdale, Ariz. 33. Dr Donald Levy, MD, Orange, Calif. 34. Clinical Allergy and Immunology Section, University of California San Diego School of Medicine, La Jolla, Calif. 35. CSL Behring, Marburg, Germany. 36. CSL Behring LLC, King of Prussia, Pa.
Abstract
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.
RCT Entities:
BACKGROUND: For the prevention of attacks of hereditary angioedema (HAE), the efficacy and safety of subcutaneous humanC1-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.
Authors: Anthony J Castaldo; Christian Jervelund; Deborah Corcoran; Henrik B Boysen; Sandra C Christiansen; Bruce L Zuraw Journal: Allergy Asthma Proc Date: 2021-02-13 Impact factor: 2.587
Authors: Marcus Maurer; Markus Magerl; Stephen Betschel; Werner Aberer; Ignacio J Ansotegui; Emel Aygören-Pürsün; Aleena Banerji; Noémi-Anna Bara; Isabelle Boccon-Gibod; Konrad Bork; Laurence Bouillet; Henrik Balle Boysen; Nicholas Brodszki; Paula J Busse; Anette Bygum; Teresa Caballero; Mauro Cancian; Anthony J Castaldo; Danny M Cohn; Dorottya Csuka; Henriette Farkas; Mark Gompels; Richard Gower; Anete S Grumach; Guillermo Guidos-Fogelbach; Michihiro Hide; Hye-Ryun Kang; Allen P Kaplan; Constance H Katelaris; Sorena Kiani-Alikhan; Wei-Te Lei; Richard F Lockey; Hilary Longhurst; William Lumry; Andrew MacGinnitie; Alejandro Malbran; Inmaculada Martinez Saguer; Juan José Matta Campos; Alexander Nast; Dinh Nguyen; Sandra A Nieto-Martinez; Ruby Pawankar; Jonathan Peter; Grzegorz Porebski; Nieves Prior; Avner Reshef; Marc Riedl; Bruce Ritchie; Farrukh Rafique Sheikh; William B Smith; Peter J Spaeth; Marcin Stobiecki; Elias Toubi; Lilian Agnes Varga; Karsten Weller; Andrea Zanichelli; Yuxiang Zhi; Bruce Zuraw; Timothy Craig Journal: World Allergy Organ J Date: 2022-04-07 Impact factor: 5.516
Authors: Donald S Levy; Henriette Farkas; Marc A Riedl; Florence Ida Hsu; Joel P Brooks; Marco Cicardi; Henrike Feuersenger; Ingo Pragst; Avner Reshef Journal: Allergy Asthma Clin Immunol Date: 2020-02-04 Impact factor: 3.406
Authors: Donald Levy; Teresa Caballero; Iftikhar Hussain; Avner Reshef; John Anderson; James Baker; Lawrence B Schwartz; Marco Cicardi; Subhransu Prusty; Henrike Feuersenger; Ingo Pragst; Michael E Manning Journal: Pediatr Allergy Immunol Pulmonol Date: 2020-09-16 Impact factor: 1.349