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About the Authors

Headshot Anne Ellis 2019

Anne K. Ellis, MD, MSc, FRCP(C), FAAAAI

Dr. Ellis is a Professor of Medicine and Chair of the Division of Allergy & Immunology at Queen’s University. She holds the James H. Day Chair in Allergic Diseases and Allergy Research. She is the Director of the Environmental Exposure Unit and the Allergy Research Unit at Kingston General Hospital. She is the current Vice President of the Canadian Society of Allergy and Clinical Immunology and serves on the Joint Task Force for Practice Parameters, representing the American College of Allergy, Asthma, and Immunology. 

Headshot Sophia Linton 2019

Sophia Linton BSc, PhD Candidate, Translational Medicine

Sophia Linton is a PhD Candidate within the Department of Medicine’s Translational Medicine Program at Queen’s University. Her research focuses the role of the local microbiome in allergic rhinitis using experimental models such as the Nasal Allergen Challenge developed by AllerGen’s Clinical Investigator Collaborative (CIC)-Allergic Rhinitis (AR). 

Future of Allergic Rhinitis Management: A synopsis


Allergic rhinitis (AR) is an inflammatory condition affecting the nasal mucosa mediated by immunoglobulin-E (IgE).1 It impacts an estimated 25% of Canadians, of whom most report inadequate symptom control despite treatment as well as high rates of asthma comorbidity.2 First line pharmacologic options include non-sedating, 2nd generation oral H1-antihistamine (OAH) and/or intranasal corticosteroid (INCS) therapeutic agents. Allergen immunotherapy (AIT) is a possible treatment option for moderate-to-severe disease which is uncontrolled with the use of first-line therapies or for those patients wishing to avoid pharmacologic intervention. However, patient education, engagement, and empowerment are central to optimal clinical outcomes. This supplement summarizes the literature to present the future of AR management.  

Mobile Health (mHealth): 

The Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines provide specific recommendations for the pharmacotherapeutic management of AR. In 2020, the guidelines were updated using a Grading of Recommendations, Assessments, Development and Evaluation (GRADE)-based approach coupled with real-world evidence (RWE).3 This RWE was obtained using the Mobile Airways Sentinel Network (MASK), a mHealth tool that is available on both the Apple and Google Play App stores and is designed for AR patients and health care providers to monitor disease symptomology and medication utilization.4 Data from two large-scale MASK studies (> 9000 users) included patient behaviours related to adherence and treatment efficacy. The results demonstrated low treatment adherence among subjects and that MPAzeFlu, an azelastine–fluticasone propionate combination, was deemed the most effective, while OAHs were deemed to be the least effective category of medication.5,6 According to the World Health Organization, mHealth tools can transform the delivery of health services, and AR is no exception.7 Still, there are limitations to mHealth apps like MASK, such as potential biases and the inability to precisely characterize patients and impact treatment adherence; however, the novel information these tools provide and their ability to collect large-scale data is unprecedented.3 


Combination formulations of intranasal H1 antihistamines (IAH) and INCS are a new drug class representing AR management’s future. Specifically, MP-AzeFlu (DYMISTA®) is an azelastine–fluticasone propionate combination formulated as a nasal spray. It is indicated for moderate-to-severe seasonal AR (SAR) in adults and children. MP-AzeFlu is more efficacious than INCS and IAH monotherapy and has a fast onset |of action.8,9 Several European non-interventional studies have evaluated the effectiveness of MP-AzeFlu in patients with ARIA-defined moderate-to-severe AR.10–14 Results from one pan-European study (n = 2988, aged ≥ 12 years) demonstrated a significant reduction (p < 0.001) in Visual Analogue Scale (VAS) scores compared with baseline from day 1 until the last day of the study (day 14).13 Studies in Sweden, Denmark, and Romania mirror these findings supporting the efficacy of MP-AzeFlu across differing geographies, age, phenotype, and severity of disease.10–12 A similar multinational study also examined patients with comorbid asthma (n=267) and found improved VAS scores across all outcome measures, including asthma symptom severity (MP-AzeFlu is not indicated for the treatment of asthma in Canada), sleep quality, daily work or school activities, daily social activities, and daily outdoor activities.14 Finally, a 2-year, pre-post, historical cohort study used data from the Optimum Patient Care Research Database to assess the effect of MP-AzeFlu on asthma outcomes in 1,188 patients with AR and asthma. More patients had well-controlled asthma after 1-year of MP-AzeFlu utilization (p = 0.0037), regardless of reduced INCS use.15 Together, these real-world studies demonstrate the beneficial clinical effects of MP-AzeFlu for moderate-to-severe AR. Canadian data on MP-AzeFlu is limited, except for a small representation (users, n=17) in the MASK study,6 and should be the focus of future research.  

GSP301 is a fixed-dose combination nasal spray containing olopatadine hydrochloride and mometasone furoate monohydrate that was submitted to Health Canada in 2020. In 2019, the safety and efficacy of GSP301 were assessed using a pooled analysis from three natural-allergen exposure studies and an environmental exposure chamber study. GSP301 twice-daily treatments resulted in significantly and clinically meaningful nasal symptom improvements vs. placebo (p < 0.001), olopatadine (p < 0.01), and mometasone (p ≤ 0.001) and was well-tolerated.16 

Allergen Immunotherapy:

AIT is a preventative, disease-modifying therapy indicated for moderate-to-severe AR. It consists of giving multiple doses of an allergen to achieve clinical tolerance, thereby reducing clinical symptoms. In Canada, AIT is approved to be administered as subcutaneous immunotherapy (SCIT) by injection or as sublingual immunotherapy (SLIT) in oral form. SLIT tablets for several allergens have been developed to manage AR, and in 2020, Health Canada approved the once-daily SQ Tree SLIT tablets (ITULATEKTM) for the treatment of tree pollen allergy. It is indicated for the treatment of moderate-to-severe AR induced by birch tree, alder, and/or hazel pollen. The results from a randomized, double-blind, placebo-controlled phase III trial (n=634, age 12-65) demonstrated that treatment with SQ Tree SLIT tablets significantly reduced the daily combined score compared to placebo (p < 0.0001) and was well-tolerated by patients.17 

In 2021, our group performed a cost-minimization analysis to estimate the economic impact of SQ Tree SLIT-tablets compared with other AIT options, such as SCIT, which is available in Canada. The direct costs for three years of treatment (drug and physician services costs) were similar for both SQ Tree SLIT tablets vs. Tree Pollen SCIT. However, treatment with
SQ Tree SLIT tablets costs less when the indirect costs (including patient’s travel expenses and lost working hours) are included in the model and, therefore should be considered a cost-minimizing alternative to Tree Pollen SCIT.18 This result mirrors our group’s earlier finding on the cost-minimizing potential of house dust mite SLIT.19

Dual treatment with grass (GRASTEK®) and ragweed (RAGWITEK®) SLIT tablets is another important consideration for the future management of AR. One open-label, multicenter trial (NCT02256553) assessed a 4-week sequential SLIT tablet dosing schedule followed by a simultaneous intake of grass and ragweed tablets and found it was safe and well-tolerated.20 Future research should focus on combining allergens for SLIT. 

Peptide Immunotherapy:

An area of continued research interest for AR management is synthetic peptide immunotherapy epitopes (SPIREs) – short synthetic peptides derived from specific allergens. Although not approved in Canada, treatment with grass allergen peptides has been shown to improve AR symptoms  after 3 intervening grass pollen seasons, corresponding to up to 2 years off treatment.21 However, future large and adequately powered real-world studies are required. 


Dupilumab (DUPIXENT®) is a monoclonal antibody (mAb) that targets interleukin (IL)-4Rα, a common receptor for IL-4 and IL-13, and thus inhibits the actions of both of these Type 2 cytokines. It is indicated in Canada for the treatment of asthma, atopic dermatitis, and chronic rhinosinusitis. Recently, two trials have investigated its use in perennial AR (PAR), specifically on asthma patients with comorbid PAR (n > 1000). Both studies demonstrated improved symptom scores after treatment with dupilumab (200 or 300 mg every 2 weeks), suggesting that dupilumab as an adjunctive therapy to systemic asthma therapy may improve treatment outcomes in these patients.22,23

Omalizumab (XOLAIR®) is a recombinant, humanized, monoclonal antibody against IgE indicated for adults and pediatric patients with moderate-to-severe persistent asthma with PAR whose symptoms are inadequately controlled with inhaled corticosteroids. A systematic review and meta-analysis of clinical trials of omalizumab for uncontrolled AR has demonstrated a significant reduction in daily nasal symptom severity score (p < 0.0001) and a statistically significant reduction in daily nasal rescue medication score p = 0.01). There are clinical trials underway investigating the use of omalizumab for AR, including pre-seasonal treatment effects (NCT0448912151)24 and the use of omalizumab in patients with severe-to-most-severe seasonal AR aged ≥ 12 years and < 18 years (NCT04648930).25

Due to the cost of biologics, AR is unlikely to become a primary indication for these therapeutic agents. However, the knowledge of established benefit for AR patients with on-label comorbidities can help shape AR management.


Advances in disease management for AR patients are focused on mHealth tools, combination pharmacotherapies, and new SLIT tablets. However, emerging trial data on peptide immunotherapies and RWE on the impact of biologic treatment options are occurring rapidly for AR. These approaches, combined with patient education remain pivotal to successful integrated care.

Figure 1. Future of Allergic Rhinitis Management Diagram

Table 1. Summary of the Aforementioned Therapies Involved in the Management of AR


  1. Bousquet J, Khaltaev N, Cruz AA, et al. Allergic Rhinitis and its Impact on Asthma (ARIA) 2008 update (in collaboration with the World Health Organization, GA2LEN and AllerGen). Allergy: European Journal of Allergy and Clinical Immunology. Published online 2008. doi:10.1111/j.1398-9995.2007.01620.x
  2. Keith PK, Desrosiers M, Laister T, Schellenberg RR, Waserman S. The burden of allergic rhinitis (AR) in Canada: perspectives of physicians and patients. Allergy, Asthma and Clinical Immunology. 2012;8(1):7. doi:10.1186/1710-1492-8-7
  3. Bousquet J, Schünemann HJ, Togias A, et al. 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. J Allergy Clin Immunol. 2020;145(1):70-80.e3. doi:10.1016/J.JACI.2019.06.049
  4. Bousquet J, Hellings PW, Agache I, et al. ARIA 2016: Care pathways implementing emerging technologies for predictive medicine in rhinitis and asthma across the life cycle. Clinical and Translational Allergy. 2016;6(1):1-14. doi:10.1186/S13601-016-0137-4/FIGURES/3
  5. Menditto E, Costa E, Midão L, et al. Adherence to treatment in allergic rhinitis using mobile technology. The MASK Study. Clinical & Experimental Allergy. 2019;49(4):442-460. doi:10.1111/CEA.13333
  6. Bédard A, Basagaña X, Anto JM, et al. Mobile technology offers novel insights into the control and treatment of allergic rhinitis: The MASK study. Journal of Allergy and Clinical Immunology. 2019;144(1):135-143.e6. doi:10.1016/J.JACI.2019.01.053
  7. Santo K, Richtering SS, Chalmers J, Thiagalingam A, Chow CK, Redfern J. Mobile phone apps to improve medication adherence: A systematic stepwise process to identify high-quality apps. JMIR Mhealth Uhealth. 2016;4(4). doi:10.2196/mhealth.6742
  8. Berger W, Bousquet J, Fox AT, et al. MP-AzeFlu is more effective than fluticasone propionate for the treatment of allergic rhinitis in children. Allergy. 2016;71(8):1219-1222. doi:10.1111/ALL.12903
  9. Berger WE, Shah S, Lieberman P, et al. Long-term, Randomized Safety Study of MP29-02 (a Novel Intranasal Formulation of Azelastine Hydrochloride and Fluticasone Propionate in an Advanced Delivery System) in Subjects With Chronic Rhinitis. The Journal of Allergy and Clinical Immunology: In Practice. 2014;2(2):179-185. doi:10.1016/J.JAIP.2013.09.019
  10. Agache I, Doros IC, Leru PM, Bucur I, Poenaru M, Sarafoleanu C. MP-AzeFlu provides rapid and effective allergic rhinitis control: results of a non-interventional study in Romania. Rhinology. 2018;56(1):33-41. doi:10.4193/RHIN16.278
  11. Haahr PA, Jacobsen C, Christensen ME. MP-AzeFlu provides rapid and effective allergic rhinitis control: results of a non-interventional study in Denmark. International Forum of Allergy & Rhinology. 2019;9(4):388-395. doi:10.1002/ALR.22258
  12. Stjärne P, Strand V, Theman K, Ehnhage A. Control of allergic rhinitis with MP-AzeFlu: a noninterventional study of a Swedish cohort. Rhinology. 2019;57(4):279-286. doi:10.4193/RHIN18.028
  13. Klimek L, Bachert C, Stjärne P, et al. MP-AzeFlu provides rapid and effective allergic rhinitis control in real life: A pan-European study. Allergy Asthma Proc. 2016;37(5):376-386. doi:10.2500/AAP.2016.37.3979
  14. Price D, Klimek L, Gálffy G, et al. Allergic rhinitis and asthma symptoms in a real-life study of MP-AzeFlu to treat multimorbid allergic rhinitis and asthma. Clinical and Molecular Allergy. Published online 2020. doi:10.1186/s12948-020-00130-9
  15. de Jong HJI, Voorham J, Scadding GK, et al. Evaluating the real-life effect of MP-AzeFlu on asthma outcomes in patients with allergic rhinitis and asthma in UK primary care. World Allergy Organization Journal. Published online 2020. doi:10.1016/j.waojou.2020.100490
  16. Gross GN, Amar NJ, Fernando N, Caracta CF, Tantry SK. Olopatadine/Mometasone Combination Nasal Spray for the Treatment of Seasonal Allergic Rhinitis: A Pooled Analysis of Efficacy and Safety. Journal of Allergy and Clinical Immunology. Published online 2019. doi:10.1016/j.jaci.2018.12.191
  17. Biedermann T, Kuna P, Panzner P, et al. The SQ tree SLIT-tablet is highly effective and well tolerated: Results from a randomized, double-blind, placebo-controlled phase III trial. Journal of Allergy and Clinical Immunology. 2019;143(3):1058-1066.e6. doi:10.1016/J.JACI.2018.12.1001
  18. Ellis AK, Gagnon R, Hammerby E, Shen J, Gosain S. Sublingual immunotherapy tablet: a cost-minimizing alternative in the treatment of tree pollen-induced seasonal allergic rhinitis in Canada. Allergy, Asthma and Clinical Immunology. 2021;17(1):1-9. doi:10.1186/S13223-021-00565-Y/FIGURES/1
  19. Ellis AK, Gagnon R, Hammerby E, Lau A. Sublingual immunotherapy tablet for the treatment of house dust mite allergic rhinitis in Canada: An alternative to minimize treatment costs? Allergy, Asthma and Clinical Immunology. 2019;15(1):1-9. doi:10.1186/S13223-019-0344-3/FIGURES/1
  20. Maloney J, Berman G, Gagnon R, et al. Sequential Treatment Initiation with Timothy Grass and Ragweed Sublingual Immunotherapy Tablets Followed by Simultaneous Treatment Is Well Tolerated. The Journal of Allergy and Clinical Immunology: In Practice. 2016;4(2):301-309.e2. doi:10.1016/J.JAIP.2015.11.004
  21. Ellis AK, Frankish CW, Armstrong K, et al. Persistence of the clinical effect of grass allergen peptide immunotherapy after the second and third grass pollen seasons. Journal of Allergy and Clinical Immunology. Published online 2020. doi:10.1016/j.jaci.2019.09.010
  22. Weinstein SF, Katial R, Jayawardena S, et al. Efficacy and safety of dupilumab in perennial allergic rhinitis and comorbid asthma. Journal of Allergy and Clinical Immunology. Published online 2018. doi:10.1016/j.jaci.2017.11.051
  23. Busse WW, Maspero JF, Lu Y, et al. Efficacy of dupilumab on clinical outcomes in patients with asthma and perennial allergic rhinitis. Annals of Allergy, Asthma and Immunology. Published online 2020. doi:10.1016/j.anai.2020.05.026
  24. The Efficacy of Preseasonal Omalizumab Treatment – Full Text View – Accessed April 21, 2022.
  25. Special Drug Use Observational Study of Xolair in Patients With Severe to Most Severe Seasonal Allergic Rhinitis Aged ≥ 12 Years and < 18 Years Whose Symptoms Were Inadequately Controlled Despite to Conventional Therapies – Full Text View – Accessed April 21, 2022.