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Published in: Clinical and Translational Allergy 1/2017

Open Access 01-12-2017 | Research

Effectiveness and safety of antihistamines up to fourfold or higher in treatment of chronic spontaneous urticaria

Authors: Mignon T. van den Elzen, Harmieke van Os-Medendorp, Imke van den Brink, Karin van den Hurk, Ouliana I. Kouznetsova, Alexander S. H. J. Lokin, Anna-Marijke Laheij-de Boer, Heike Röckmann, Carla A. F. M. Bruijnzeel-Koomen, André C. Knulst

Published in: Clinical and Translational Allergy | Issue 1/2017

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Abstract

Background

Treatment with second-generation antihistamines is recommended in patients with chronic spontaneous urticaria (CSU). Some patients remain unresponsive even after up-dosing up to fourfold. Many third line treatment options have limited availability and/or give rise to significant side effects. We investigated effectiveness and safety of antihistamine treatment with dosages up to fourfold and higher.

Methods

This retrospective analysis of patients’ records was performed in adult CSU patients suffering wheals and/or angioedema (AE). Demographic, clinical, and therapeutic data was extracted from their medical records. We recorded the type, maximum prescribed dosage, effectiveness, and reported side effects of antihistamine treatment.

Results

Of 200 screened patients, 178 were included. Treatment was commenced with a once daily dose of antihistamines. Persisting symptoms meant that up-dosing up to fourfold occurred in 138 (78%) of patients, yielding sufficient response in 41 (23%). Up-dosing antihistamines was necessary in 110 (80%) patient with weals alone or weals with angioedema and 28 (64%) with AE only (p = 0.039). Of the remaining 97 patients with insufficient response, 59 were treated with dosages higher than fourfold (median dosage 8, range 5–12). This was sufficient in 29 patients (49%). Side effects were reported in 36 patients (20%), whereof 30 (17%) experienced somnolence. Side effects after up-dosing higher than fourfold were reported in six out of 59 patients (10%).

Conclusion

Up-dosing antihistamines higher than fourfold dosage seems a feasible therapeutic option with regards to effectiveness and safety. The need for third line therapies could be decreased by 49%, with a very limited increase of reported side effects.
Literature
1.
go back to reference Zuberbier T, Aberer W, Asero R, Bindslev-Jensen C, Brzoza Z, Canonica GW, et al. The EAACI/GA(2) LEN/EDF/WAO guideline for the definition, classification, diagnosis, and management of urticaria: the 2013 revision and update. Allergy. 2014;69:868–87. doi:10.1111/all.12313.CrossRefPubMed Zuberbier T, Aberer W, Asero R, Bindslev-Jensen C, Brzoza Z, Canonica GW, et al. The EAACI/GA(2) LEN/EDF/WAO guideline for the definition, classification, diagnosis, and management of urticaria: the 2013 revision and update. Allergy. 2014;69:868–87. doi:10.​1111/​all.​12313.CrossRefPubMed
2.
5.
go back to reference Maurer M, Weller K, Bindslev-Jensen C, Giménez-Arnau A, Bousquet PJ, Bousquet J, et al. Unmet clinical needs in chronic spontaneous urticaria. A GA2LEN task force report. Allergy Eur J Allergy Clin Immunol. 2011;66:317–30.CrossRef Maurer M, Weller K, Bindslev-Jensen C, Giménez-Arnau A, Bousquet PJ, Bousquet J, et al. Unmet clinical needs in chronic spontaneous urticaria. A GA2LEN task force report. Allergy Eur J Allergy Clin Immunol. 2011;66:317–30.CrossRef
8.
go back to reference Weller K, Ziege C, Staubach P, Brockow K, Siebenhaar F, Krause K, et al. H 1-antihistamine up-dosing in chronic spontaneous urticaria: patients’ perspective of effectiveness and side effects—a retrospective survey study. PLoS ONE. 2011;6:1–6.CrossRef Weller K, Ziege C, Staubach P, Brockow K, Siebenhaar F, Krause K, et al. H 1-antihistamine up-dosing in chronic spontaneous urticaria: patients’ perspective of effectiveness and side effects—a retrospective survey study. PLoS ONE. 2011;6:1–6.CrossRef
9.
go back to reference Staevska M, Popov TA, Kralimarkova T, Lazarova C, Kraeva S, Popova D, et al. The effectiveness of levocetirizine and desloratadine in up to 4 times conventional doses in difficult-to-treat urticaria. J Allergy Clin Immunol. 2010;125:676–82. doi:10.1016/j.jaci.2009.11.047.CrossRefPubMed Staevska M, Popov TA, Kralimarkova T, Lazarova C, Kraeva S, Popova D, et al. The effectiveness of levocetirizine and desloratadine in up to 4 times conventional doses in difficult-to-treat urticaria. J Allergy Clin Immunol. 2010;125:676–82. doi:10.​1016/​j.​jaci.​2009.​11.​047.CrossRefPubMed
10.
go back to reference Giménez-Arnau A, Izquierdo I, Maurer M. The use of a responder analysis to identify clinically meaningful differences in chronic urticaria patients following placebo-controlled treatment with rupatadine 10 and 20 mg. J Eur Acad Dermatol Venereol. 2009;23:1088–91.CrossRefPubMed Giménez-Arnau A, Izquierdo I, Maurer M. The use of a responder analysis to identify clinically meaningful differences in chronic urticaria patients following placebo-controlled treatment with rupatadine 10 and 20 mg. J Eur Acad Dermatol Venereol. 2009;23:1088–91.CrossRefPubMed
14.
go back to reference Dubertret L, Zalupca L, Cristodoulo T, Benea V, Medina I, Fantin S, et al. Once-daily rupatadine improves the symptoms of chronic idiopathic urticaria: a randomised, double-blind, placebo-controlled study. Eur J Dermatol. 2007;17:223–8. doi:10.1684/ejd.2007.0153.PubMed Dubertret L, Zalupca L, Cristodoulo T, Benea V, Medina I, Fantin S, et al. Once-daily rupatadine improves the symptoms of chronic idiopathic urticaria: a randomised, double-blind, placebo-controlled study. Eur J Dermatol. 2007;17:223–8. doi:10.​1684/​ejd.​2007.​0153.PubMed
16.
go back to reference Metz M, Scholz E, Ferrán M, Izquierdo I, Giménez-Arnau A, Maurer M. Rupatadine and its effects on symptom control, stimulation time, and temperature thresholds in patients with acquired cold urticaria. Ann Allergy Asthma Immunol. 2010;104:86–92. doi:10.1016/j.anai.2009.11.013.CrossRefPubMed Metz M, Scholz E, Ferrán M, Izquierdo I, Giménez-Arnau A, Maurer M. Rupatadine and its effects on symptom control, stimulation time, and temperature thresholds in patients with acquired cold urticaria. Ann Allergy Asthma Immunol. 2010;104:86–92. doi:10.​1016/​j.​anai.​2009.​11.​013.CrossRefPubMed
17.
go back to reference Siebenhaar F, Degener F, Zuberbier T, Martus P, Maurer M. High-dose desloratadine decreases wheal volume and improves cold provocation thresholds compared with standard-dose treatment in patients with acquired cold urticaria: a randomized, placebo-controlled, crossover study. J Allergy Clin Immunol. 2009;123:672–9. doi:10.1016/j.jaci.2008.12.008.CrossRefPubMed Siebenhaar F, Degener F, Zuberbier T, Martus P, Maurer M. High-dose desloratadine decreases wheal volume and improves cold provocation thresholds compared with standard-dose treatment in patients with acquired cold urticaria: a randomized, placebo-controlled, crossover study. J Allergy Clin Immunol. 2009;123:672–9. doi:10.​1016/​j.​jaci.​2008.​12.​008.CrossRefPubMed
18.
go back to reference Zuberbier T, Aberer W, Burtin B, Rihoux JP, Czarnetzki BM. Efficacy of cetirizine in cholinergic urticaria. Acta Derm Venereol. 1995;75:147–9.PubMed Zuberbier T, Aberer W, Burtin B, Rihoux JP, Czarnetzki BM. Efficacy of cetirizine in cholinergic urticaria. Acta Derm Venereol. 1995;75:147–9.PubMed
21.
go back to reference Finn AF, Kaplan AP, Fretwell R, Qu R, Long J. A double-blind, placebo-controlled trial of fexofenadine HCl in the treatment of chronic idiopathic urticaria. J Allergy Clin Immunol. 1999;104:1071–8.CrossRefPubMed Finn AF, Kaplan AP, Fretwell R, Qu R, Long J. A double-blind, placebo-controlled trial of fexofenadine HCl in the treatment of chronic idiopathic urticaria. J Allergy Clin Immunol. 1999;104:1071–8.CrossRefPubMed
22.
go back to reference Paul E, et al. Fexofenadine hydrochloride in the treatment of chronic idiopathic urticaria: a placebo-controlled, parallel-group, dose-ranging study. J Dermatol Treat. 1998;9(3):143–9.CrossRef Paul E, et al. Fexofenadine hydrochloride in the treatment of chronic idiopathic urticaria: a placebo-controlled, parallel-group, dose-ranging study. J Dermatol Treat. 1998;9(3):143–9.CrossRef
23.
go back to reference Weller K, Viehmann K, Bräutigam M, Krause K, Siebenhaar F, Zuberbier T, et al. Management of chronic spontaneous urticaria in real life—in accordance with the guidelines? A cross-sectional physician-based survey study. J Eur Acad Dermatol Venereol. 2013;27:43–50.CrossRefPubMed Weller K, Viehmann K, Bräutigam M, Krause K, Siebenhaar F, Zuberbier T, et al. Management of chronic spontaneous urticaria in real life—in accordance with the guidelines? A cross-sectional physician-based survey study. J Eur Acad Dermatol Venereol. 2013;27:43–50.CrossRefPubMed
25.
go back to reference Staevska M, Gugutkova M, Lazarova C, Kralimarkova T, Dimitrov V, Zuberbier T, et al. Night-time sedating H1-antihistamine increases daytime somnolence but not treatment efficacy in chronic spontaneous urticaria: a randomized controlled trial. Br J Dermatol. 2014;171:148–54.CrossRefPubMedPubMedCentral Staevska M, Gugutkova M, Lazarova C, Kralimarkova T, Dimitrov V, Zuberbier T, et al. Night-time sedating H1-antihistamine increases daytime somnolence but not treatment efficacy in chronic spontaneous urticaria: a randomized controlled trial. Br J Dermatol. 2014;171:148–54.CrossRefPubMedPubMedCentral
26.
go back to reference Grattan C. Night-time sedating H1-antihistamine increases daytime somnolence but not treatment efficacy in chronic spontaneous urticaria: a randomized controlled trial. Br J Dermatol. 2014;171:8–9.CrossRefPubMed Grattan C. Night-time sedating H1-antihistamine increases daytime somnolence but not treatment efficacy in chronic spontaneous urticaria: a randomized controlled trial. Br J Dermatol. 2014;171:8–9.CrossRefPubMed
28.
go back to reference Richardson GS, Roehrs TA, Rosenthal L, Koshorek G, Roth T. Tolerance to daytime sedative effects of H1 antihistamines. J Clin Psychopharmacol. 2002;22:511–5.CrossRefPubMed Richardson GS, Roehrs TA, Rosenthal L, Koshorek G, Roth T. Tolerance to daytime sedative effects of H1 antihistamines. J Clin Psychopharmacol. 2002;22:511–5.CrossRefPubMed
29.
go back to reference Balp M-M, Vietri J, Tian H, Isherwood G. The impact of chronic urticaria from the patient’s perspective: a survey in five European countries. Patient Patient Cent Outcomes Res. 2015;8:551–8. doi:10.1007/s40271-015-0145-9.CrossRef Balp M-M, Vietri J, Tian H, Isherwood G. The impact of chronic urticaria from the patient’s perspective: a survey in five European countries. Patient Patient Cent Outcomes Res. 2015;8:551–8. doi:10.​1007/​s40271-015-0145-9.CrossRef
Metadata
Title
Effectiveness and safety of antihistamines up to fourfold or higher in treatment of chronic spontaneous urticaria
Authors
Mignon T. van den Elzen
Harmieke van Os-Medendorp
Imke van den Brink
Karin van den Hurk
Ouliana I. Kouznetsova
Alexander S. H. J. Lokin
Anna-Marijke Laheij-de Boer
Heike Röckmann
Carla A. F. M. Bruijnzeel-Koomen
André C. Knulst
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Clinical and Translational Allergy / Issue 1/2017
Electronic ISSN: 2045-7022
DOI
https://doi.org/10.1186/s13601-017-0141-3

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