Intranasal Corticosteroids in Allergic Rhinitis: Indian ENT Perspective and Utility of Fluticasone Furoate

Allergic Rhinitis (AR), one of the most prevalent types of chronic rhinitis, has marked symptoms of nasal congestion, itching, rhinorrhoea, sneezing, and anosmia in patients with severe obstruction. Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines have categorized AR into intermittent AR with symptoms lasting < 4 weeks and persistent AR with symptoms for > 4 weeks duration (1, 2). AR has a prevalence of about 20% globally, while in India, it affects 10-30% of the population (3).

The Allergic response in Allergic Rhinitis (AR):

Allergic Rhinitis (AR) is primarily an immunoglobulin E (IgE) mediated inflammatory response. Leukotrienes and prostaglandins, bradykinins, and platelet-activating factors are some mediators released in the early phase when exposed to an allergen. These mediators lead to nasal congestion, rhinorrhea, itching, and sneezing due to vasodilation, increased vascular permeability, mucus secretion stimulation, and afferent nerve stimulation within 30 minutes of exposure. After about 4–24 hours after exposure, T-lymphocyte activation and production of T helper 2-type (TH-2) cytokines and tissue eosinophilia occur, known as the late phase response (4).

Management of Allergic Rhinitis (AR):

Allergic Rhinitis (AR) is a complex disease, and its management reflects this complexity. Accurate diagnosis, allergen avoidance, and pharmacotherapy are the mainstays of AR management. Nonsedating antihistamines, intranasal corticosteroids (INCS), and corticosteroids with antihistamine intranasal combinations are the first line of treatment for AR. Additional treatment options encompass leukotriene receptor antagonists, mast cell stabilizers, decongestants, and cromolyn (5).

AR leads to potential long-term clinical implications. About 15% of AR cases progress to asthma, sinusitis, and otitis media. It also affects the quality of life, causing learning and attention impairment. Hence, there is a need to address AR in affected individuals as it can reduce the burden of upper and lower respiratory tract infections. Studies have shown that topical steroids are more effective than topical and systemic antihistamines for managing nasal symptoms (6,7).

Novel Action of Intranasal Corticosteroids (INCS):

Intranasal corticosteroids (INCS) are potent pharmacotherapeutic agents in managing and alleviating symptoms of AR in both early and late-phase reactions. INCS relieves symptoms like nasal congestion, itching, rhinorrhea, and sneezing and may almost eliminate late-phase symptoms (4). INCS has a complex mechanism of action on nasal mucosal target cells. Their main target is the epithelial cells. INCS combines with the steroid receptors on the cellular surface and expels the dead epithelial cells and inflammatory cells into the airway lumen. They also exhibit mild effects on the mediator influx, reducing the symptoms (8).

Rationale of Considering Intranasal Corticosteroids (INCS) in Allergic Rhinitis (AR):

Intranasal Corticosteroids (INCS) are highly effective and can deliver adequate drug concentrations directly to the epithelial cell receptor sites in the nasal mucosa (4,7). They can effectively control the symptoms with minimal systemic effects. (4). INCS are preferred first-line treatment not only in mild cases but in moderate to severe and persistent AR as well, applicable for both seasonal and perennial AR in adults and children. In individuals having comorbid asthma with AR, INCS are the preferred drugs. INCS are also safe as they do not cause suppression of the hypothalamic-pituitary-adrenal axis (HPAA) (7). Among the various corticosteroids available, fluticasone furoate is one of them.

Fluticasone Furoate spray in Allergic Rhinitis (AR):

Fluticasone furoate (FF) is a novel, topical, intranasal, enhanced-affinity trifluorinated corticosteroid with potent anti-inflammatory activity and low systemic toxicity. It can be used both for seasonal and perennial AR. It has been found highly effective in reducing nasal symptoms in children ≥2 years, adolescents, and adults. It is available as an aqueous suspension of micronized FF in a nasal spray for topical administration to the nasal mucosa using a metering, atomizing spray pump. It has a striking ability to reduce the ocular symptoms in seasonal and perennial AR (9).

Fluticasone Furoate: Review of Literature:

Fluticasone is as efficacious as other INCS: A prospective, comparative study was carried out on 135 AR patients in an ENT department. They compared the safety profile of INCS on 45 patients in each group - Mometasone Furoate {(MF),200 micrograms once daily}, Fluticasone Furoate {(FF), 110 micrograms once daily}, and Fluticasone Propionate {(FP), 200 micrograms once daily} in AR. Nasal symptoms were evaluated using a Visual Analog Scale of 1 to 10, Nasal endoscopy score (based on discharge, mucosal color, edema), absolute eosinophil count, and adverse events every week for four weeks. The study found that the average decrease in the symptoms and nasal endoscopy scores was significant and similar in all three groups. Thus, the study concluded that all three INCS benefitted AR (10)

Fluticasone furoate nasal spray for pediatric AR: Another double-blind, placebo-controlled, multicenter randomized controlled study examined the efficacy and safety of fluticasone furoate nasal spray (FFNS) in the pediatric population. Patients were randomized 1:1:1 to receive either FFNS 55 µg or 110 µg or placebo and recorded their symptoms using electronic diary cards. They experienced a significantly greater reduction in daily reflective total nasal symptom score (congestion), and FFNS was well tolerated in both dosages. Thus, the study concluded that FFNS was effective and tolerable, supporting its use in the pediatric population (11).

Take Home points:

• Allergic Rhinitis (AR) is an IgE-mediated inflammatory response with early and late-phase reactions due to mediators like Leukotrienes and prostaglandins, bradykinins, and platelet-activating factors.
• INCS is highly effective in managing AR. INCS targets the nasal epithelial cells and reduces the symptoms of nasal congestion, sneezing, itching, and rhinorrhea.
• Fluticasone furoate is a potent INCS with high anti-inflammatory activity and low systemic toxicity.
• Fluticasone furoate is considered safe, efficacious, and well-tolerated even in the pediatric population.

References:

1. Larenas-Linnemann DES, Domthong P, Di Francesco RC, González-Pérez R, Verma M. General practitioner and patient perspectives on intranasal corticosteroids for allergic rhinitis: Treatment duration and obstacles to adherence, findings from a recent survey. World Allergy Organ J. 2024;17(7):100925. Published 2024 Jun 25. doi:10.1016/j.waojou.2024.100925.

2. Small, P., Keith, P.K. & Kim, H. Allergic rhinitis. Allergy Asthma Clin Immunol 14 (Suppl 2), 51 (2018). https://doi.org/10.1186/s13223-018-0280-7.

3. S M, M KK. Prescription trends and patterns for allergic rhinitis treatment in clinical practice. International Journal of Otolaryngology Sciences. 2024;6(1):01-05. doi:https://doi.org/10.33545/26649225.2024.v6.i1a.9.

4. Trangsrud AJ, Whitaker AL, Small RE. Intranasal Corticosteroids for Allergic Rhinitis. Pharmacotherapy. 2002;22(11):1458-1467. doi:https://doi.org/10.1592/phco.22.16.1458.33692.

5. Linton S, Burrows AG, Hossenbaccus L, Ellis AK. Future of allergic rhinitis management. Annals of Allergy, Asthma & Immunology: Official Publication of the American College of Allergy, Asthma, & Immunology. 2021;127(2):183-190. doi:https://doi.org/10.1016/j.anai.2021.04.029

6. Narasimhan, R., Roy, S., Koralla, M. et al. Expert Panel Consensus Recommendations for Allergic Rhinitis in Patients with Asthma in India. Pulm Ther (2024). https://doi.org/10.1007/s41030-024-00273-z

7. van Cauwenberge P, Bachert C, Passalacqua G, et al. Consensus statement on the treatment of allergic rhinitis. European Academy of Allergology and Clinical Immunology. Allergy. 2000;55(2):116-134. doi:10.1034/j.1398-9995.2000.00526.x

8. Mygind N, Nielsen LP, Hoffmann HJ, et al. Mode of action of intranasal corticosteroids. J Allergy Clin Immunol. 2001;108(1 Suppl):S16-S25. doi:10.1067/mai.2001.115561.

9‌. Rodrigo GJ, Neffen H. Efficacy of fluticasone furoate nasal spray vs. placebo for the treatment of ocular and nasal symptoms of allergic rhinitis: a systematic review. Clinical & Experimental Allergy. 2010;41(2):160-170. doi:https://doi.org/10.1111/j.1365-2222.2010.03654.x

10. Faiz S mohd, Gupta RK, Saurabh Srivastav. SAFETY PROFILE OF INTRANASAL CORTICOSTEROIDS USED AS TREATMENT IN ALLERGIC RHINITIS PATIENTS ATTENDING ENT OPD AT A TERTIARY CARE CENTRE: A COMPARATIVE STUDY. doi:https://doi.org/10.21176/ojolhns.

11. Zhang Y, Wei P, Chen B, et al. Intranasal fluticasone furoate in pediatric allergic rhinitis: randomized controlled study. Pediatr Res. 2021;89(7):1832-1839. doi:10.1038/s41390-020-01180-0