Review: Intranasal corticosteroids in Allergic rhinitis

Allergic Rhinitis is one of the most common persistent conditions for which clinical intervention is sought and is a significant cause of widespread morbidity.

It affects between 10% and 30% of all adults and as many as 40% of children globally (1).

The incidence of chronic allergic rhinitis has gradually risen in the last two decades. And it significantly affects the development and severity of other disorders, including bronchial asthma, sinusitis, middle ear disease, and dental malocclusion adds the disease burden. (2).

The primary non-pharmacologic treatment for allergic rhinitis is avoiding the offending agent which is somewhat difficult for individuals with the perennial disorder since they have continuous exposure to allergens.

Consequently, pharmacotherapy plays an important role in managing symptoms of Allergic Rhinitis (3).

Intranasal corticosteroids are recommended as first-line therapy for the treatment of persistent moderate to severe allergic rhinitis by the Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines (4). Even the standard guideline for the management of allergic rhinitis in India issued by the Ministry of Health and Family Welfare recommended the use of Fluticasone furoate as a nasal spray in outpatient treatment.

In general, intranasal corticosteroids relieve nasal congestion and itching, rhinorrhea, and sneezing, and in some studies, they almost completely prevented late-phase symptoms (3). Intranasal corticosteroids have been shown to be more effective than the combined use of an antihistamine and leukotriene (LT) antagonist in the treatment of seasonal allergic rhinitis (1).

Intranasal corticosteroids also cause a reduction in the number of inflammatory cells and Th2-type cytokines within the nasal mucosa of patients with allergic rhinitis thereby reducing the antigen-induced hyper-responsiveness of the nasal mucosa to subsequent antigen and histamine provocation. On the basis of these favorable anti-inflammatory effects of intranasal corticosteroids, several placebo-controlled clinical trials using a variety of these agents demonstrated their effectiveness in the reduction of all nasal symptoms in both seasonal and perennial allergic rhinitis (2).

Intranasal corticosteroids over other Allergic Rhinitis Therapy

The major benefit of intranasal corticosteroids administration is that high concentrations of the drug, with a quick onset of action; Intranasal corticosteroids start to include impacts within 7 to 8 hours of dosing, albeit some reports show an impact within 2 hours (2). They can be conveyed directly into the target organ so that systemic effects are limited. Intranasal corticosteroids exert their anti-inflammatory impact through the inhibition of the production of many different cytokines, chemokines, enzymes, and cell adhesion molecules, after their interaction with intracellular glucocorticoid receptors (5). Intranasal corticosteroids when given in recommended doses are not commonly tied with clinically significant systemic side effects which add its supremacy over other therapy accessible for allergic rhinitis (1).

Several intranasal corticosteroids are available beclomethasone, dipropionate, budesonide, flunisolide, fluticasone propionate, mometasone furoate, and triamcinolone acetonide and fluticasone furoate as nasal spray (3). To compare the efficacy and safety profile of different available intranasal corticosteroids for the treatment of allergic rhinitis, it is important to understand the different structures and their pharmacokinetic and pharmacodynamic properties (5).

Some important pharmacokinetic parameters in intranasal corticosteroids are prodrug design, organ deposition, the onset of action, lipophilicity, bioavailability, systemic clearance, protein binding, the volume of distribution, a device of administration, and nasal residence time (5).

Fluticasone furoate over other Intranasal corticosteroids

Fluticasone furoate is a new, topical, intranasal, enhanced-affinity trifluorinated glucocorticoid, with potent anti-inflammatory activity and low systemic exposure. It has high receptor affinity, and greater relative receptor affinity (2989).

It has been approved by FDA in the year 2007 for the treatment of symptoms of seasonal allergic rhinitis and perennial allergic rhinitis in adults and children two years of age and older (6).

Fluticasone furoate nasal spray displayed high selectivity for the glucocorticoid receptor in vitro and had no effect on the hypothalamic pituitary-adrenal (HPA) axis in children or adults during clinical trials (5).

Studies supporting Fluticason furoate nasal spray in Allergic Rhinitis

1. Fokkins et.al (2007) carried out a randomized, parallel-group study in patients [adults and adolescents above 12 years of age] with seasonal allergic rhinitis. Participants received once-daily (od) treatment for 2 weeks with either fluticasone furoate nasal spray 110 µg or placebo nasal spray. Fluticasone furoate nasal spray 110 µg was effective in improving the nasal symptoms of seasonal allergic rhinitis. It also produced significant improvements in ocular symptoms (7).

2. Nathan et.al (2007) analyzed the efficacy of fluticasone furoate nasal spray, novel enhanced affinity steroids, in treating perineal allergic rhinitis in adults and adolescents. Participants were treated with fluticasone furoate nasal spray 110mcg or vehicle placebo for four weeks. Fluticasone furoate nasal spray was administered via a unique, side-actuated device. The result demonstrated that fluticasone furoate nasal spray is clinically significant for nasal symptoms of perineal allergic rhinitis in adults and adolescents. It sustained 24-hour efficacy with no safety issues identified (8).

3. Andrew et. al (2009) conducted a randomized, double-blind study to compare fluticasone furoate nasal spray (110 µg) and the commonly prescribed oral antihistamine fexofenadine (180 µg) with respect to nighttime sleep disturbance caused by seasonal allergy symptoms. Within a period of two weeks study, they concluded that fluticasone furoate nasal spray improved all three components of the nighttime nasal symptoms score—nasal congestion on awakening, nighttime awakenings due to nasal symptoms, and difficulty sleeping due to nasal symptoms. Fluticasone furoate nasal spray (110 µg) was significantly more effective than fexofenadine, 180 µg, once daily at improving nighttime nasal allergy symptoms and at least comparable in improving nighttime ocular symptoms (4).

4. Kumar et.al, in their review paper summarizes the clinical data on fluticasone furoate nasal spray and its role in the management of allergic rhinitis. The paper noted that more patients preferred fluticasone furoate as a nasal spray to fluticasone propionate based on attributes of scent or odor (58% vs. 27%), aftertaste (60% vs. 18%), leaking out of the nose and down the throat (59% vs. 21%), and mist gentleness (57% vs. 26%). Furthermore, the paper noted the safety and tolerability of fluticasone furoate nasal spray for daily use and availability in a side-actuated device that makes medication delivery simple and consistent (6).

Key points

• The role of intranasal corticosteroids in the treatment of allergic rhinitis is well established. They are shown to be efficacious and are recommended as first-line therapy for individuals with persistent moderate/ severe rhinitis.

• Fluticasone furoate nasal spray is a new topical corticosteroid, with enhanced affinity and a unique side-actuated delivery device, which is effective in improving nasal symptoms of Allergic Rhinitis.

• Fluticasone furoate nasal spray with high topical potency, low potential for systemic effects, low systemic bioavailability, 24-h symptom relief with once-daily dosing, comprehensive coverage of both nasal and ocular symptoms is a good candidate amongst available intranasal steroids for rhinitis treatment.

References:

1. Wallace DV et al., Journal of allergy and clinical immunology. 2008 Aug 1;122(2):S1-84.

2. https://www.clinicalkey.com/#!/content/book/3-s2.0-B9780323544245000411?scrollTo=%23hl0001088

3. Amanda J. Trangsrud, Amy L. Whitaker, and Ralph E. Small. Intranasal Corticosteroids for Allergic Rhinitis. Pharmacotherapy 2002

4. Andrews, C. P., Martin, B. G., Jacobs, R. L., Mohar, D. E., Diaz, J. D., Amar, et.al, Fluticasone furoate nasal spray is more effective than fexofenadine for nighttime symptoms of seasonal allergy. 2009. Allergy and asthma proceedings.

5. Goyal N, Hochhaus G. Fluticasone furoate nasal spray in allergic rhinitis. Drugs Today (Barc). 2008;44(4):251-260.

6. Kumar R, Kumar D, Parakh A. Fluticasone furoate: A new intranasal corticosteroid. J Postgrad Med 2012;58:79-83

7. Fokkens, W. J., Jogi, R., Reinartz, S., Sidorenko, I., Sitkauskiene, B., van Oene, C.,et.al. Once daily fluticasone furoate nasal spray is effective in seasonal allergic rhinitis caused by grass pollen. 2007. Allergy, 62(9), 1078–1084.

8. R. Nathan, W. Berger, W. Yang, A. Cheema, M. J. Silvey, W. Wu, et.al. Once Daily Fluticasone Furoate* Nasal Spray (FFNS), a Novel Enhanced Affinity Steroid, Provides 24-hour Relief for the Nasal Symptoms of Perennial Allergic Rhinitis (PAR).2007. Journal of Allergy and Clinical Immunology.