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

Publication date: Available online 23 December 2016
Source:Journal of Allergy and Clinical Immunology
Author(s): Marco Cicardi, Andrea Zanichelli, Chiara Suffritti, Maddalena A. Wu, Thomas Machnig, Annalisa De Silvestri, Mario Regazzi, Carmine Tinelli
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.

Teaser

Pharmacokinetic data in a patient with poor treatment response to plasma-derived C1 inhibitor compared with 17 control patients suggest that poor treatment response likely depends on increased catabolism, but not through interaction with target proteases.


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