Levocetirizine better protects than desloratadine in a nasal provocation with allergen

doi:10.1016/j.jaci.2004.01.773

Journal of Allergy and Clinical Immunology

Volume 113, Issue 4, April 2004, Pages 669-676

https://doi.org/10.1016/j.jaci.2004.01.773 Get rights and content

Abstract

Background

Direct comparisons of antihistamines are rare but very much needed. Newly available antihistamine preparations, levocetirizine, the R-enantiomer of racemate cetirizine, and desloratadine, an active metabolite of loratadine, have been recently released for allergic rhinitis.

Objective

We sought to compare levocetirizine and desloratadine in a nasal provocation test (NPT) with grass pollen.

Methods

Twenty-four volunteers with grass pollen allergy and a history of rhinitis were enrolled in a double-blind, placebo-controlled, crossover study. Three NPTs were performed in a dose-escalating manner during the out-of-season period 4 hours after a single dose of levocetirizine (5 mg), desloratadine (5 mg), or placebo.

Results

Differences in the mean allergen dose level (primary end point) necessary to reach the NPT threshold indicated improved protection provided by levocetirizine compared with that provided by desloratadine (P = .02). Sneezing and rhinorrhea were better inhibited by levocetirizine than desloratadine. Nasal congestion, as assessed by using objective methods, was not limited by either active substances or placebo. In nasal lavage fluid, IL-5, IL-8, eotaxin, and eosinophil cationic protein levels increased at 24 hours, without differences between the groups. In contrast, levocetirizine, but not desloratadine, significantly limited albumin extravasation into nasal lavage fluid in the early-phase response.

Conclusions

This study demonstrates a better overall protection of a single dose of levocetirizine compared with desloratadine in an NPT with grass pollen allergen. In contrast to late-phase inflammatory markers, which were unaffected, extravascular leakage of the early-phase marker albumin was significantly limited by levocetirizine.

Section snippets

Patients

Twenty-four volunteers with a history of grass pollen–induced rhinitis were enrolled in the study on the basis of the following inclusion criteria: (1) age between 18 and 60 years; (2) a positive history of allergic rhinitis during the latest pollen season confirmed by means of either a positive skin prick test response (wheal diameter >3 mm)¹⁰ or specific IgE for grass pollen (>0.70 kU/L) as titrated with a sandwich immunoassay (UniCAP; Pharmacia Diagnostics, Uppsala, Sweden); and (3) a nasal

Volunteers

Forty-three volunteers were screened. Fifteen were excluded because of allergic rhinitis (n = 13) to tree pollens and to perennial allergens, as detected by means of history, skin prick tests, or both, or because of a nonspecific nasal reaction at the inclusion NPT (n = 2). Twenty-four volunteers were initially enrolled, of whom 4 dropped out and were subsequently replaced. Three of them stopped the study after the first trial period (1 from each treatment phase) because of the discomfort generated

Discussion

This article is the first report comparing the R-enantiomer of cetirizine, levocetirizine, with desloratadine, a metabolite of loratadine, in an NPT with grass pollen allergen. Although levocetirizine appeared superior to desloratadine in 2 recent histamine-induced skin reaction studies, skin reactivity to histamine cannot be used as a surrogate model for allergic rhinits.17., 18., 19., 20., 21., 22. In the present study both desloratadine and levocetirizine were administrated 4 hours before

Acknowledgements

We thank Mr Gloor Stephane, Hospital pharmacist, for the preparation of the opaque capsules and for the randomization. We thank Drs T. Buclin, B. Burnand, and J. Cornuz for their support in statistical analysis.

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Background: Nasal congestion is the most troublesome symptom of allergic rhinitis (AR). First-generation and older second-generation antihistamines, while effective against nasal itching, sneezing, and rhinorrhea, have limited efficacy in relieving nasal congestion.
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Results: Twenty-six clinical trials met the criteria for inclusion in the review. In 11 placebo-controlled trials that included objective assessment of nasal congestion, desloratadine, fexofenadine, and levocetiri-zine were associated with reductions in the severity of nasal congestion through maintenance of nasal airflow. The mean AUC for nasal airflow over 6 hours was significantly greater with desloratadine compared with placebo in 3 studies (P < 0.05); placebo-controlled trials of fexofenadine and levocetirizine had similar results. In 25 placebo- and active-controlled trials that reported subject-rated symptom scores, the 3 newer antihistamines were efficacious in the treatment of nasal congestion associated with AR. In 10 trials that reported objective and/or subjective measures, desloratadine was associated with significant improvements in nasal congestion compared with placebo (P ≤ 0.05), beginning as early as the first 2 hours after allergen challenge. Fexofenadine was associated with significantly lower nasal congestion scores compared with placebo in 4 studies (P <- 0.05); nasal congestion scores were significantly reduced with levocetirizine in 3 placebo-controlled trials (P ≤ 0.005).
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Supplementary data associated with this article can be found at doi:10.1016/j.jaci.2004.01.773.

Supported by Fondation pour la recherche en immunologie, Lausanne, Switzerland.

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Asthma, rhinitis, other respiratory diseasesLevocetirizine better protects than desloratadine in a nasal provocation with allergen☆

Abstract

Background

Objective

Methods

Results

Conclusions

Section snippets

Patients

Volunteers

Discussion

Acknowledgements

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Levocetirizine better protects than desloratadine in a nasal provocation with allergen☆