New Patents of Fixed Combinations of Nasal Antihistamines and Corticosteroids in Allergic Rhinitis

Ole   D.   Wolthers

Abstract

During the last few years, fixed combinations of intranasal antihistamines and corticosteroids have been introduced for treatment of allergic rhinitis. The aim of this systematic review was to assess recent patents and clinical evidence for fixed combinations of intranasal antihistamines and intranasal corticosteroids in allergic rhinitis. Data base searches revealed that intranasal combinations of the antihistamine azelastine with the corticosteroids mometasone furoate, ciclesonide and fluticasone propionate, respectively, have been patented. Four randomized, double-blinded, parallelgroup, placebo-controlled, multicenter trials sponsored by the manufacturer evaluated the fixed combination of intranasal azelastine 125µg and fluticasone propionate 50µg administered as one dose per nostril b.i.d. in patients with moderate-tosevere symptomatic allergic rhinitis ≥ 12 years of age. Three of the studies were published as a meta-analysis which found the fixed combination of azelastine and fluticasone propionate statistically significantly more efficacious in reducing baseline total nasal symptom score by 5.7 as compared to azelastine (4.4; P < 0.001), fluticasone propionate (5.1; P < 0.001) and placebo (3.0; P < 0.001). The findings were supported by secondary assessments of scores of specific nasal and ocular symptoms. Pharmacokinetic studies have revealed no drug-drug interactions but a discrete increase in bioavailability of fluticasone propionate which was considered clinically unimportant. Further efficacy and quality-of-life studies of combination products of nasal antihistamines and corticosteroids are needed, especially, in primary care settings and in children before fixed combination treatment can be considered first line therapy in allergic rhinitis. Fixed combination treatment of azelastine and fluticasone propionate may offer additional benefit to selected populations of adolescents and adults with moderate-to-severe symptoms.

Keywords: Allergic rhinitis, allergic rhinoconjunctivitis, allergy, antihistamines, azelastine, ciclesonide, combination therapy, fluticasone propionate, mometasone, nasal corticosteroids.