Skip to main content
Top
Published in: Allergy, Asthma & Clinical Immunology 1/2017

Open Access 01-12-2017 | Research

Breakthrough attacks in patients with hereditary angioedema receiving long-term prophylaxis are responsive to icatibant: findings from the Icatibant Outcome Survey

Authors: Werner Aberer, Marcus Maurer, Laurence Bouillet, Andrea Zanichelli, Teresa Caballero, Hilary J. Longhurst, Amandine Perrin, Irmgard Andresen, for the IOS Study Group

Published in: Allergy, Asthma & Clinical Immunology | Issue 1/2017

Login to get access

Abstract

Background

Patients with hereditary angioedema (HAE) due to C1-inhibitor deficiency (C1-INH-HAE) experience recurrent attacks of cutaneous or submucosal edema that may be frequent and severe; prophylactic treatments can be prescribed to prevent attacks. However, despite the use of long-term prophylaxis (LTP), breakthrough attacks are known to occur. We used data from the Icatibant Outcome Survey (IOS) to evaluate the characteristics of breakthrough attacks and the effectiveness of icatibant as a treatment option.

Methods

Data on LTP use, attacks, and treatments were recorded. Attack characteristics, treatment characteristics, and outcomes (time to treatment, time to resolution, and duration of attack) were compared for attacks that occurred with versus without LTP.

Results

Data on 3228 icatibant-treated attacks from 448 patients with C1-INH-HAE were analyzed; 30.1% of attacks occurred while patients were using LTP. Attack rate, attack severity, and the distribution of attack sites were similar across all types of LTP used, and were comparable to the results found in patients who did not receive LTP. Attacks were successfully treated with icatibant; 82.5% of all breakthrough attacks were treated with a single icatibant injection without C1-INH rescue medication. Treatment outcomes were comparable for breakthrough attacks across all LTP types, and for attacks without LTP.

Conclusions

Patients who use LTP should be aware that breakthrough attacks can occur, and such attacks can be severe. Thus, patients with C1-INH-HAE using LTP should have emergency treatment readily available. Data from IOS show that icatibant is effective for the treatment of breakthrough attacks.
Trial Registration NCT01034969
Literature
2.
go back to reference Zuraw BL, Bernstein JA, Lang DM, Craig T, Dreyfus D, Hsieh F, et al. A focused parameter update: hereditary angioedema, acquired C1 inhibitor deficiency, and angiotensin-converting enzyme inhibitor-associated angioedema. J Allergy Clin Immunol. 2013;131:1491–3.CrossRefPubMed Zuraw BL, Bernstein JA, Lang DM, Craig T, Dreyfus D, Hsieh F, et al. A focused parameter update: hereditary angioedema, acquired C1 inhibitor deficiency, and angiotensin-converting enzyme inhibitor-associated angioedema. J Allergy Clin Immunol. 2013;131:1491–3.CrossRefPubMed
3.
go back to reference Cicardi M, Bork K, Caballero T, Craig T, Li HH, Longhurst H, et al. Evidence-based recommendations for the therapeutic management of angioedema owing to hereditary C1 inhibitor deficiency: consensus report of an International Working Group. Allergy. 2012;67:147–57.CrossRefPubMed Cicardi M, Bork K, Caballero T, Craig T, Li HH, Longhurst H, et al. Evidence-based recommendations for the therapeutic management of angioedema owing to hereditary C1 inhibitor deficiency: consensus report of an International Working Group. Allergy. 2012;67:147–57.CrossRefPubMed
4.
go back to reference Craig T, Aygören-Pürsün E, Bork K, Bowen T, Boysen H, Farkas H, et al. WAO guideline for the management of hereditary angioedema. World Allergy Organ J. 2012;5:182–99.CrossRefPubMedPubMedCentral Craig T, Aygören-Pürsün E, Bork K, Bowen T, Boysen H, Farkas H, et al. WAO guideline for the management of hereditary angioedema. World Allergy Organ J. 2012;5:182–99.CrossRefPubMedPubMedCentral
5.
go back to reference Cicardi M, Aberer W, Banerji A, Bas M, Bernstein JA, Bork K, et al. Classification, diagnosis, and approach to treatment for angioedema: consensus report from the Hereditary Angioedema International Working Group. Allergy. 2014;69:602–16.CrossRefPubMed Cicardi M, Aberer W, Banerji A, Bas M, Bernstein JA, Bork K, et al. Classification, diagnosis, and approach to treatment for angioedema: consensus report from the Hereditary Angioedema International Working Group. Allergy. 2014;69:602–16.CrossRefPubMed
6.
go back to reference Longhurst HJ, Tarzi MD, Ashworth F, Bethune C, Cale C, Dempster J, et al. C1 inhibitor deficiency: 2014 United Kingdom consensus document. Clin Exp Immunol. 2015;180:475–83.CrossRefPubMedPubMedCentral Longhurst HJ, Tarzi MD, Ashworth F, Bethune C, Cale C, Dempster J, et al. C1 inhibitor deficiency: 2014 United Kingdom consensus document. Clin Exp Immunol. 2015;180:475–83.CrossRefPubMedPubMedCentral
7.
go back to reference Zuraw BL, Kalfus I. Safety and efficacy of prophylactic nanofiltered C1-inhibitor in hereditary angioedema. Am J Med. 2012;125(9):938.e1–7.CrossRef Zuraw BL, Kalfus I. Safety and efficacy of prophylactic nanofiltered C1-inhibitor in hereditary angioedema. Am J Med. 2012;125(9):938.e1–7.CrossRef
8.
go back to reference Reshef A, Moldovan D, Obtulowicz K, Leibovich I, Mihaly E, Visscher S, et al. Recombinant human C1 inhibitor for the prophylaxis of hereditary angioedema attacks: a pilot study. Allergy. 2013;68:118–24.CrossRefPubMed Reshef A, Moldovan D, Obtulowicz K, Leibovich I, Mihaly E, Visscher S, et al. Recombinant human C1 inhibitor for the prophylaxis of hereditary angioedema attacks: a pilot study. Allergy. 2013;68:118–24.CrossRefPubMed
9.
go back to reference Pedrosa M, Lobera T, Panizo C, Jurado J, Caballero T. Long-term prophylaxis with C1-inhibitor concentrate in patients with hereditary angioedema. J Investig Allergol Clin Immunol. 2014;24:271–3.PubMed Pedrosa M, Lobera T, Panizo C, Jurado J, Caballero T. Long-term prophylaxis with C1-inhibitor concentrate in patients with hereditary angioedema. J Investig Allergol Clin Immunol. 2014;24:271–3.PubMed
10.
go back to reference Gelfand JA, Sherins RJ, Alling DW, Frank MM. Treatment of hereditary angioedema with danazol: reversal of clinical and biochemical abnormalities. N Engl J Med. 1976;295:1444–8.CrossRefPubMed Gelfand JA, Sherins RJ, Alling DW, Frank MM. Treatment of hereditary angioedema with danazol: reversal of clinical and biochemical abnormalities. N Engl J Med. 1976;295:1444–8.CrossRefPubMed
11.
go back to reference Sheffer AL, Fearon DT, Austen KF. Clinical and biochemical effects of stanozolol therapy for hereditary angioedema. J Allergy Clin Immunol. 1981;68:181–7.CrossRefPubMed Sheffer AL, Fearon DT, Austen KF. Clinical and biochemical effects of stanozolol therapy for hereditary angioedema. J Allergy Clin Immunol. 1981;68:181–7.CrossRefPubMed
12.
go back to reference Maurer M, Aberer W, Bouillet L, Caballero T, Fabien V, Kanny G, et al. Hereditary angioedema attacks resolve faster and are shorter after early icatibant treatment. PLoS ONE. 2013;8:e53773.CrossRefPubMedPubMedCentral Maurer M, Aberer W, Bouillet L, Caballero T, Fabien V, Kanny G, et al. Hereditary angioedema attacks resolve faster and are shorter after early icatibant treatment. PLoS ONE. 2013;8:e53773.CrossRefPubMedPubMedCentral
13.
go back to reference Longhurst HJ, Aberer W, Bouillet L, Caballero T, Fabien V, Zanichelli A, et al. Analysis of characteristics associated with reinjection of icatibant: results from the Icatibant Outcome Survey. Allergy Asthma Proc. 2015;36:399–406.CrossRefPubMed Longhurst HJ, Aberer W, Bouillet L, Caballero T, Fabien V, Zanichelli A, et al. Analysis of characteristics associated with reinjection of icatibant: results from the Icatibant Outcome Survey. Allergy Asthma Proc. 2015;36:399–406.CrossRefPubMed
14.
go back to reference Zuraw BL, Busse PJ, White M, Jacobs J, Lumry W, Baker J, et al. Nanofiltered C1 inhibitor concentrate for treatment of hereditary angioedema. N Engl J Med. 2010;363:513–22.CrossRefPubMed Zuraw BL, Busse PJ, White M, Jacobs J, Lumry W, Baker J, et al. Nanofiltered C1 inhibitor concentrate for treatment of hereditary angioedema. N Engl J Med. 2010;363:513–22.CrossRefPubMed
15.
go back to reference Bork K, Bygum A, Hardt J. Benefits and risks of danazol in hereditary angioedema: a long-term survey of 118 patients. Ann Allergy Asthma Immunol. 2008;100:153–61.CrossRefPubMed Bork K, Bygum A, Hardt J. Benefits and risks of danazol in hereditary angioedema: a long-term survey of 118 patients. Ann Allergy Asthma Immunol. 2008;100:153–61.CrossRefPubMed
16.
go back to reference Zanichelli A, Wu MA, Andreoli A, Mansi M, Cicardi M. The safety of treatments for angioedema with hereditary C1 inhibitor deficiency. Expert Opin Drug Saf. 2015;14:1725–36.CrossRefPubMed Zanichelli A, Wu MA, Andreoli A, Mansi M, Cicardi M. The safety of treatments for angioedema with hereditary C1 inhibitor deficiency. Expert Opin Drug Saf. 2015;14:1725–36.CrossRefPubMed
17.
go back to reference Longhurst HJ, Aberer W, Bouillet L, Caballero T, Maurer M, Fabien V, et al. The Icatibant Outcome Survey: treatment of laryngeal angioedema attacks. Eur J Emerg Med. 2016;23:224–7.CrossRefPubMed Longhurst HJ, Aberer W, Bouillet L, Caballero T, Maurer M, Fabien V, et al. The Icatibant Outcome Survey: treatment of laryngeal angioedema attacks. Eur J Emerg Med. 2016;23:224–7.CrossRefPubMed
18.
go back to reference Zanichelli A, Mansi M, Azin GM, Wu MA, Periti G, Casazza G, et al. Efficacy of on-demand treatment in reducing morbidity in patients with hereditary angioedema due to C1 inhibitor deficiency. Allergy. 2015;70:1553–8.CrossRefPubMed Zanichelli A, Mansi M, Azin GM, Wu MA, Periti G, Casazza G, et al. Efficacy of on-demand treatment in reducing morbidity in patients with hereditary angioedema due to C1 inhibitor deficiency. Allergy. 2015;70:1553–8.CrossRefPubMed
20.
go back to reference Aygören-Pürsün E, Magerl M, Martinez-Saguer I. C1 inhibitor for routine prophylaxis in patients with hereditary angioedema: interim results from a European registry study. J Allergy Clin Immunol. 2016;137(suppl 2):AB251.CrossRef Aygören-Pürsün E, Magerl M, Martinez-Saguer I. C1 inhibitor for routine prophylaxis in patients with hereditary angioedema: interim results from a European registry study. J Allergy Clin Immunol. 2016;137(suppl 2):AB251.CrossRef
Metadata
Title
Breakthrough attacks in patients with hereditary angioedema receiving long-term prophylaxis are responsive to icatibant: findings from the Icatibant Outcome Survey
Authors
Werner Aberer
Marcus Maurer
Laurence Bouillet
Andrea Zanichelli
Teresa Caballero
Hilary J. Longhurst
Amandine Perrin
Irmgard Andresen
for the IOS Study Group
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Allergy, Asthma & Clinical Immunology / Issue 1/2017
Electronic ISSN: 1710-1492
DOI
https://doi.org/10.1186/s13223-017-0203-z

Other articles of this Issue 1/2017

Allergy, Asthma & Clinical Immunology 1/2017 Go to the issue