Present and Potential Therapy for Allergic Rhinitis

Abstract

Allergic rhinitis can affect up to one-fifth of the population and the economic impact is increasing. H(1) receptor antagonists were the first major pharmacologic treatment, but the associated sedation limited their use. The 2 initial second generation less sedating antihistamines, astemizole and terfenadine, were found to prolong the cardiac QT(c) interval, especially when administered with other medications metabolised by the same cytochrome (CYP) P450 isoenzyme, CYP3A4. Other second generation antihistamines, fexofenadine, loratadine and cetirizine, do not cause clinically significant cardiac QT(c) interval prolongation. Two newer agents, ebastine and mizolastine, are also effective in the treatment of allergic rhinitis. Ebastine, however, prolongs the cardiac QT(c) interval in laboratory animals and humans, the clinical significance of which is unknown. Desloratadine and norastemizole, metabolites of loratadine and astemizole, respectively, are 2 other second generation antihistamines found to be effective treatments for seasonal allergic rhinitis. Unlike their parent compounds, they do not prolong the cardiac QT(c) interval. All clinically available intranasal corticosteroids are effective in the treatment of allergic rhinitis, but studies to evaluate possible long term systemic adverse effects are limited. Mometasone furoate and fluticasone propionate have lower oral bioavailability compared with other corticosteroids that are given intranasally. This may be important, since it is likely that some of the intranasal corticosteroid is ingested. Two 1-year growth studies in children indicated that intranasal beclomethasone dipropionate given twice daily reduces growth velocity, whereas intranasal mometasone furoate given once daily in the morning does not. Other studies are needed. Most but not all studies have shown that leukotriene antagonists are effective in the treatment of allergic rhinitis. H(1) receptor antagonists are not very effective in reducing nasal congestion, but leukotriene antagonists do attenuate this symptom. Furthermore, one study demonstrates an additive benefit in treating allergic rhinitis with the combination of a H(1) receptor and leukotriene antagonist. Clinical trials have demonstrated that anti-immunoglobulin (Ig) E is effective in the treatment of seasonal allergic rhinitis when free IgE is reduced to <25 microg/L. The reduction of total IgE is dose dependent and subcutaneous and intravenous administration are both effective. Immunotherapy is also an effective treatment for allergic rhinitis. CpG oligonucleotides is a novel adjuvant for allergen immunotherapy. This adjuvant used in a murine model shifts the immune response away from the allergic or TH2 phenotype. Studies in humans have not been performed.