The complex pathophysiology of allergic rhinitis: scientific rationale for the development of an alternative treatment option

Abstract

Allergic rhinitis (AR) poses a global health problem and can be challenging to treat. Many of the current symptomatic treatments for AR have been available for decades, yet there has been little improvement in patient quality of life or symptom burden over the years. In this review, we ask why this might be and explore the pathophysiological gaps that exist within the various AR treatment classes. We focus on the benefits and drawbacks of different treatment options and delivery routes for AR treatments and consider how, given what is known about AR pathophysiology and symptomatology, patients may be offered more effective treatment options for rapid, effective, and sustained AR control. In particular, we consider how a new AR preparation, MP-AzeFlu (Dymista^®, Meda, Sweden), comprising a formulation of an intranasal antihistamine (azelastine hydrochloride), an intranasal corticosteroid (fluticasone propionate), and excipients delivered in a single spray, may offer benefits over and above single and multiple AR therapy options. We review the evidence in support of this treatment across the spectrum of AR disease. The concept of AR control is also reviewed within the context of new European Union and Contre les Maladies Chroniques pour un VIeillissement Actif-Allergic Rhinitis and its Impact on Asthma initiatives.

Keywords: Allergic rhinitis; Azelastine; Fluticasone; MP-AzeFlu.

Fig. 1

Early and late phases showing the pathophysiological processes and drivers of allergic rhinitis and the potential sites for pharmacological intervention. ECP eosinophil cationic protein, ICAM-1 intercellular adhesion molecule-1, IgE immunoglobulin E, IL interleukin

Fig. 2

Change from baseline in reflective total nasal symptom score (rTNSS), reflective total ocular symptom score (rTOSS), and reflective total of seven symptom scores (rT7SS) following 14 days’ treatment with MP-AzeFlu (n = 153), fluticasone propionate (FP; n = 151), or azelastine hydrochloride (AZE; n = 152). LS least squares, MP-AzeFlu a novel formulation of an intranasal antihistamine, azelastine, and an intranasal corticosteroid, fluticasone propionate, in a single spray. The precision of these estimates is indicated by the upper bounds of the respective 95% confidence intervals. *p ≤ 0.0031 versus MP-AzeFlu. ^†p ≤ 0.0004 versus MP-AzeFlu (Modified from Meltzer et al. [118])

Fig. 3

Effect of MP-AzeFlu (n = 388, blue) and fluticasone propionate (FP; n = 199, orange) on reflective total nasal symptom score (rTNSS) in patients with chronic rhinitis. Data are presented as least squares (LS) mean change from baseline at 4-week intervals. MP-AzeFlu a novel formulation of an intranasal antihistamine, azelastine hydrochloride, and an intranasal corticosteroid, fluticasone propionate, in a single spray, rTNSS, reflective total nasal symptom score. *p ≤ 0.0453 versus MP-AzeFlu (Adapted with permission from the Journal of Investigational Allergology and Clinical Immunology)

Fig. 4

Least squares (LS) mean change from baseline in reflective total nasal symptom score (rTNSS; am + pm) per day when most children (n = 82; > 90%) rated their own symptoms following treatment with MP-AzeFlu or placebo, both one spray per nostril twice daily, for 14 days in children aged 6–11 years with moderate-severe SAR. MP-AzeFlu a novel formulation of an intranasal antihistamine, azelastine hydrochloride, and an intranasal corticosteroid, fluticasone propionate, in a single spray, SAR seasonal allergic rhinitis. *p ≤ 0.040 versus placebo (Reprinted with permission from Berger et al. [130])

Fig. 5

Effect of MP-AzeFlu on visual analogue scale (VAS) score over time. Data presented as mean and standard deviation. AR allergic rhinitis, CDSS clinical decision support system, MP-AzeFlu, a novel formulation of an intranasal antihistamine, azelastine hydrochloride, and an intranasal corticosteroid, fluticasone propionate, in a single spray (Reprinted with permission from Klimek et al. [126])