Catabolism of C1 inhibitor influences the response to replacement therapy in hereditary angioedema

Summary Hereditary angioedema due to C1 inhibitor deficiency (C1-INH-HAE) is a disabling and life-threatening disease for which plasma-derived C1 inhibitor (pdC1-INH) is an effective treatment. Poor responses to pdC1-INH are rare. The aim of this prospective study was to evaluate the pharmacokinetic...

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Published in:Journal of allergy and clinical immunology 2017-06, Vol.139 (6), p.2005-2007.e1
Main Authors: Cicardi, Marco, M.D, Zanichelli, Andrea, M.D, Suffritti, Chiara, Ph.D, Wu, Maddalena A., M.D, Machnig, Thomas, M.D, De Silvestri, Annalisa, M.D, Regazzi, Mario, Pharm.D, Tinelli, Carmine, M.D
Format: Article
Language:English
Subjects:
Allergy and Immunology
Angioedema
Catabolism
Edema
Patients
Plasma
Protease inhibitors
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Summary:Summary Hereditary angioedema due to C1 inhibitor deficiency (C1-INH-HAE) is a disabling and life-threatening disease for which plasma-derived C1 inhibitor (pdC1-INH) is an effective treatment. Poor responses to pdC1-INH are rare. The aim of this prospective study was to evaluate the pharmacokinetics and pharmacodynamics of C1 inhibitor (C1-INH) in a C1-INH-HAE patient with poor response to treatment to investigate the mechanism underlying poor response to pdC1-INH. Seventeen C1-INH-HAE patients with normal responses to treatment served as retrospective controls. In the poor response patient, higher than standard doses of pdC1-INH did not change the PK but led to normalization of PD parameters and symptoms disappeared, recurring upon dose reduction. Therefore, we conclude that hyperactivation of the complement and contact systems in highly symptomatic C1-INH-HAE patients does not account for interpatient variability in response to pdC1-INH, which may be connected to differences in hepatic clearance of infused pdC1-INH.
ISSN:0091-6749
1097-6825
DOI:10.1016/j.jaci.2016.10.044