Decoding the role of Azelastine and Fluticasone Furoate Fixed Dose Combination Spray in Management of Allergic Rhinitis

Management of Allergic Rhinitis (AR): Analysing Current Therapeutic Options

Both nasal and non-nasal symptoms distinguish AR. Common nasal symptoms include anterior or posterior rhinorrhea, sneezing, nasal obstruction, and/or nasal itching (3). These symptoms may last many hours after exposure to allergens irritating the mucosa. Non-nasal symptoms include ocular manifestations such as allergic rhinoconjunctivitis (itching, redness, and tears of the eyes), palate irritation, postnasal drip, and cough. (4)

• Symptomatic therapies, including antihistamines (AH), nasal glucocorticoids, nasal decongestants, and leukotriene receptor antagonists, are the major pillars of AR therapy (1).
• Antihistamines which are regarded as first-line treatment for mild AR, have undergone a generational evolution with new intranasal AHs which ensure enhanced medication delivery to nasal mucosa during allergic inflammation in AR. (5)
• Intranasal corticosteroids, which act by decreasing immune cell infiltration in AR, are efficacious in both children and adults with mild and moderate-to-severe AR. (1)
• Studies indicate that 56% of AR patients continue to rely on two or more prescriptions to manage AR; integrating two medications into a single system reduces costs while significantly enhancing patient compliance.
• Among these, a novel combination of an intranasal corticosteroid (INCS) and an intranasal antihistamine (INAH) has shown substantial promise in successfully treating AR. (6) Research shows that a novel INCS/INAH combination containing Fluticasone furoate and Azelastine surpasses Fluticasone propionate sprays in terms of clinical effectiveness and practical benefits. (6,7)

Use of INCS/INAH Combination Therapy: Glance at Guidelines

Combination treatment is preferred in AR for patients who do not respond adequately to monotherapy. Several medication combinations can be utilized to treat AR. The most clinically proven effective treatment is a combination of an intranasal steroid and an intranasal antihistamine. The main advantage of combining medications over monotherapy is that it improves efficacy and symptom management. (8)

• Both the International Consensus Statement on Allergy and Rhinology and the American Academy of Otolaryngology-Head and Neck Surgery Foundation Clinical Practice Guideline for Allergic Rhinitis recommend intranasal steroid spray as first-line treatment and suggest that clinicians may offer combination therapy in patients with persistent symptoms. (8)
• Appreciating the benefits of a combination nasal spray, the new ARIA (Allergic Rhinitis and its Impact on Asthma) recommendations advocate combined therapy with an INAH and an INCS in seasonal AR. (9)
• Recognizing that up to 40% of children suffer from AR at some point, the Indian Academy of Pediatrics (IAP) recommends choosing a nasal steroid with low systemic bioavailability, like fluticasone furoate, at a minimum dose required to control symptoms. They elaborated that while the recommended dosage for fluticasone furoate for 2-11 years is 27.5 μg/nostril OD and for patients aged >12 years, it is 55 μg/nostril OD, regular monitoring is critical for the success of the therapy. (3,10)

Scientific Evidence Testimonials: What makes Azelastine and Fluticasone furoate stand out?

• Fluticasone furoate is an enhanced-affinity glucocorticoid that has been in focus for superior qualities, including a rapid onset of action compared to other INCs, 24-hour symptom relief with once-daily dosing, better patient compliance due to its unique sensory attribute and reduced aftertaste effects, availability in a novel, side-actuated delivery device that makes medication administration quick and reliable, demonstrated efficacy and safety across adults and pediatric groups aged 2–11yrs, and providing fast relief from ocular symptoms.(3,11,12,13)
• INAH-INCS combination provides a single dosage form alternative with excellent clinical symptom coverage and quicker management. Patients benefit from the synergistic effects of each molecule’s complementary mechanism of action. Administering the two agents in a single device single spray has been associated with more uniform dispersion and increased nasal cavity retention than subsequent sprays. (9)
• A comprehensive evaluation found that intranasal fluticasone and azelastine combination treatment for allergic rhinitis was more effective. The research selected eight previously published scientific publications to assess the efficacy of the two combination agents in treating allergic rhinitis. Results revealed that the total nasal symptoms score decreased further in the combination therapy group compared to the placebo. (mean change from baseline: -2.41; 95% confidence interval [CI], -2.82 to -1.99; P < .001; I2 = 60%). (14)
• A study comparing the efficacy of different INCS concluded that the onset of action for Fluticasone Furoate nasal spray was observed from the first day of treatment. This rapid onset of action of Fluticasone Furoate is due to its higher receptor affinity than Fluticasone Propionate. (6,7)

Key Pointers-

• The increasing frequency of AR and the fact that it is a tenacious illness with hampering social productivity and more chronic lower respiratory implications have directed the need for aggressive AR management pharmacotherapies.
• Among the existing pharmacotherapies, a combination of intranasal corticosteroids (INCS) and antihistamines (INAH) has shown significant success in treating AR.
• Azelastine &Fluticasone furoate intranasal spray has cemented a unique position in managing AR across all age groups.

References

1. Nur Husna, S. M., Tan, H., Md Shukri, N., Mohd Ashari, N. S., & Wong, K. K. (2022). Allergic Rhinitis: A Clinical and Pathophysiological Overview. Frontiers in Medicine, 9. https://doi.org/10.3389/fmed.2022.874114

2. Li CW, Chen DD, Zhong JT, Lin ZB, Peng H, Lu HG, et al. Epidemiological characterization and risk factors of allergic rhinitis in the general population in Guangzhou city in China. PLoS One. (2014) 9:e114950. doi: 10.1371/journal.pone.0114950

3. Meltzer EO, Lee J, Tripathy I, Lim J, Ellsworth A, Philpot E. Efficacy and safety of once-daily fluticasone furoate nasal spray in children with seasonal allergic rhinitis treated for 2 wk.Pediatr Allergy Immunol. 2009;20(3):279-286. doi:10.1111/j.1399-3038.2008.00773.x

4. Brozek JL, Bousquet J, Agache I, Agarwal A, Bachert C, Bosnic-Anticevich S, et al. Allergic rhinitis and its impact on asthma (ARIA) guidelines-2016 revision. J Allergy Clin Immunol. (2017) 140:950–8. doi: 10.1016/j.jaci.2017.03.050

5. Bjermer L, Westman M, Holmstrom M, Wickman MC. The complex pathophysiology of allergic rhinitis: scientific rationale for the development of an alternative treatment option. Allergy Asthma Clin Immunol. (2019) 15:24. doi: 10.1186/s13223-018-0314-1

6. Fowler, J., Rotenberg, B.W. & Sowerby, L.J. The subtle nuances of intranasal corticosteroids. J of Otolaryngol - Head & Neck Surg 50, 18 (2021). https://doi.org/10.1186/s40463-020-00480-z

7. Kumar R, Kumar D, Parakh A. Fluticasone furoate: A new intranasal corticosteroid. J Postgrad Med [serial online] 2012 [cited 2022 Dec 13];58:79-83. Available from: https://www.jpgmonline.com/text.asp?2012/58/1/79/93260

8. Seidman MD, Gurgel RK, Lin SY, et al. Clinical practice guideline: Allergic rhinitis.Otolaryngol Head Neck Surg. 2015;152(1 Suppl):S1-S43. doi:10.1177/0194599814561600

9. Bousquet, J., Schünemann, H. J., Togias, A., Bachert, C., Erhola, M., Hellings, P. W., ... & Its Impact on Asthma Working Group. (2020). Next-generation Allergic Rhinitis and Its Impact on Asthma (ARIA) guidelines for allergic rhinitis based on Grading of Recommendations Assessment, Development and Evaluation (GRADE) and real-world evidence. Journal of Allergy and Clinical Immunology, 145(1), 70-80.

10. R Remesh Kumar et al., Allergic Rhinitis. Standard Treatment Guidelines 2022.Available at: https://iapindia.org/pdf/Ch-014-Allergic-Rhinitis.pdf

11. Meltzer E, Andrews C, Journeay G, Lim J, Prillaman B, Garris C, et al. Comparison of patient preference for sensory attributes of fluticasone furoate or fluticasone propionate in adults with seasonal allergic rhinitis: A randomized, placebo-controlled, double-blind study.Ann Allergy Asthma Immunol 2010;104:331

12. Grossman J, Banov C, Bronsky EA, et al. Fluticasone propionate aqueous nasal spray is safe and effective for children with seasonal allergic rhinitis. Pediatrics. 1993;92(4):594-599.

13. Baroody, F. M., Shenaq, D., DeTineo, M., Wang, J., &Naclerio, R. M. (2009). Fluticasone furoate nasal spray reduces the nasal-ocular reflex: A mechanism for the efficacy of topical steroids in controlling allergic eye symptoms. Journal of Allergy and Clinical Immunology, 123(6), 1342–1348. doi:10.1016/j.jaci.2009.03.015

14. Debbaneh, P. M., Bareiss, A. K., Wise, S. K., & McCoul, E. D. (2019). Intranasal azelastine and fluticasone as combination therapy for allergic rhinitis: systematic review and meta-analysis. Otolaryngology-Head and Neck Surgery, 161(3), 412-418.