Jonathan A Bernstein1, Michael E Manning2, Henry Li3, Martha V White4, James Baker5, William R Lumry6, Mark A Davis-Lorton7, Kraig W Jacobson8, Richard G Gower9, Colin Broom10, David Fitts10, Jennifer Schranz10. 1. Division of Immunology, Allergy, and Rheumatology, and Department of Internal Medicine, University of Cincinnati, Cincinnati, Ohio. Electronic address: Jonathan.Bernstein@uc.edu. 2. Allergy, Asthma and Immunology Associates, Ltd, Scottsdale, Ariz. 3. Institute for Asthma and Allergy, Chevy Chase, Md. 4. Institute for Asthma and Allergy, Wheaton, Md. 5. Allergy Asthma & Dermatology Associates, Lake Oswego, Ore. 6. AARA Research Center, Dallas, Tex. 7. Division of Rheumatology and Immunology, Winthrop University Hospital, Mineola, NY. 8. Allergy and Asthma Research Group, Eugene, Ore. 9. Marycliff Allergy Specialists, Spokane, Wash. 10. Clinical Research for Broom and Schranz and Biostatistics for Fitts, ViroPharma Incorporated, Exton, Pa.
Abstract
BACKGROUND: Nanofiltered C1 inhibitor (human) is approved in the United States for routine prophylaxis of angioedema attacks in patients with hereditary angioedema, a rare disease caused by a deficiency of functional C1 inhibitor. OBJECTIVE: To assess the safety of escalating doses of nanofiltered C1 inhibitor (human) in patients who were not adequately controlled on the indicated dose (1000 U every 3 or 4 days). METHODS: Eligible patients had >1 attack/month over the 3 months before the trial. Doses were escalated to 1500 U every 3 or 4 days for 12 weeks, at which point, the patients were evaluated. If treatment was successful (≤1 attack/mo) or at the investigator's discretion, the patients entered a 3-month follow-up period. The patients with an average of >1 attack/month were eligible for further escalation to 2000 U and then 2500 U. RESULTS: Twenty patients started at 1500 U; 13 were escalated to 2000 U, and 12 were escalated to 2500 U. Eighteen patients reported adverse events. Two patients reported 4 serious adverse events (cerebral cystic hygroma, laryngeal angioedema attack, anemia, and bile duct stone) that were considered by investigators to be unrelated to treatment. Notably, there were no systemic thrombotic events or discontinuations due to adverse events. Fourteen patients were treated successfully (70%), continued to the follow-up period at the investigator's discretion, or experienced a reduction in attacks of >1.0/month. CONCLUSIONS: Dose escalation of nanofiltered C1 inhibitor (human) up to 2500 U was well tolerated and reduced attack frequency in the majority of patients.
BACKGROUND: Nanofiltered C1 inhibitor (human) is approved in the United States for routine prophylaxis of angioedema attacks in patients with hereditary angioedema, a rare disease caused by a deficiency of functional C1 inhibitor. OBJECTIVE: To assess the safety of escalating doses of nanofiltered C1 inhibitor (human) in patients who were not adequately controlled on the indicated dose (1000 U every 3 or 4 days). METHODS: Eligible patients had >1 attack/month over the 3 months before the trial. Doses were escalated to 1500 U every 3 or 4 days for 12 weeks, at which point, the patients were evaluated. If treatment was successful (≤1 attack/mo) or at the investigator's discretion, the patients entered a 3-month follow-up period. The patients with an average of >1 attack/month were eligible for further escalation to 2000 U and then 2500 U. RESULTS: Twenty patients started at 1500 U; 13 were escalated to 2000 U, and 12 were escalated to 2500 U. Eighteen patients reported adverse events. Two patients reported 4 serious adverse events (cerebral cystic hygroma, laryngeal angioedema attack, anemia, and bile duct stone) that were considered by investigators to be unrelated to treatment. Notably, there were no systemic thrombotic events or discontinuations due to adverse events. Fourteen patients were treated successfully (70%), continued to the follow-up period at the investigator's discretion, or experienced a reduction in attacks of >1.0/month. CONCLUSIONS: Dose escalation of nanofiltered C1 inhibitor (human) up to 2500 U was well tolerated and reduced attack frequency in the majority of patients.
Authors: Emel Aygören-Pürsün; Daniel Soteres; Dumitru Moldovan; Jim Christensen; Arthur Van Leerberghe; James Hao; Jennifer Schranz; Kraig W Jacobson; Inmaculada Martinez-Saguer Journal: Int Arch Allergy Immunol Date: 2017-06-30 Impact factor: 2.749
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: Timothy Craig; Ralph Shapiro; Arthur Vegh; James W Baker; Jonathan A Bernstein; Paula Busse; Markus Magerl; Inmaculada Martinez-Saguer; Marc A Riedl; William Lumry; Debora Williams-Herman; Jonathan Edelman; Henrike Feuersenger; Thomas Machnig; Mikhail Rojavin Journal: Allergy Rhinol (Providence) Date: 2017-03-01
Authors: Marc A Riedl; Jonathan A Bernstein; Timothy Craig; Aleena Banerji; Markus Magerl; Marco Cicardi; Hilary J Longhurst; Mustafa M Shennak; William H Yang; Jennifer Schranz; Jovanna Baptista; Paula J Busse Journal: Clin Transl Allergy Date: 2017-10-06 Impact factor: 5.871