Millions of people throughout the world suffer from allergic rhinitis. An IgE-mediated immune reaction to perennial and seasonal allergens defines allergic rhinitis. The sensitization process begins with allergen presentation to the T and B lymphocytes by macrophages and dendritic cells (antigen-presenting cells). When the sensitized patient has developed an allergy to a specific allergen, the re-exposure to the causal allergen triggers a molecular cascade that causes the clinical symptoms of allergic rhinitis. Symptoms of allergic rhinitis such as sneezing, nasal congestion/obstruction, and nasal itching, can be extremely bothersome, difficult to tolerate, and interfere with daily life. Some symptoms, such as recurrent headache and fatigue, may only appear after being exposed to allergens for an extended period [1], [2].
Present scenario of therapeutics for allergic rhinitis
The standard of care for allergic rhinitis involves:
Avoiding allergens
Pharmacotherapy
Immunotherapy
Historically, the treatment of allergic rhinitis has the main focus on relieving symptoms with medications. But the way allergic rhinitis is treated has transformed during the last decade with the development, approval, and growing use of biologics. With the growing prevalence of allergic rhinitis globally and its impact on the quality of life, new biological therapies for these diseases have become hot topics of intensive research [1], [2].
What are biologics?
Biologics are a novel class of immunotherapy drugs, which are monoclonal antibodies that target particular proteins implicated in the allergic cascade. Using biologics to treat allergic rhinitis is a brand-new and exciting field of study. Biologics have been game-changing for patients with severe asthma, after the advent of an anti-IgE monoclonal antibody as first-line therapy for patients with severe allergic asthma approximately 15 years ago. Studies in which anti-IgE was administered to patients with allergic rhinitis showed encouraging results. There are presently no FDA-approved biologics available for allergic rhinitis. However, biologics that have been investigated for the treatment of allergic rhinitis are now in development, in phase III trials, or are already on the market for other indications. In addition to the cytokine-targeting drugs that are currently available in the market, monoclonal antibodies that target specific epitopes on allergens such as cat or birch are also being investigated [1]–[3].
Omalizumab in the treatment of allergic rhinitis
Omalizumab is an anti-IgE monoclonal antibody that inhibits the inflammatory cascade after exposure to allergens by reducing the release of downstream inflammatory factors. Other allergic disorders like moderate-to-severe allergic asthma, chronic spontaneous urticaria, and severe chronic rhinosinusitis with nasal polyposis have received regulatory approval for the use of this therapeutic antibody, but allergic rhinitis has not. However, several randomized controlled trials examined the effectiveness and safety of omalizumab in treating allergic rhinitis. Omalizumab has also been shown to significantly reduce symptoms and improve the quality of life in patients with seasonal and perennial allergic rhinitis in randomized trials and real-world studies. In patients with uncontrolled allergic rhinitis, omalizumab was effective in lowering nasal symptom severity and rescue medication scores. Recent studies have looked into the effects of omalizumab alone and in combination with allergen-specific immunotherapy in the treatment of allergic rhinitis. Omalizumab has been successfully used to treat both seasonal and perennial allergic rhinitis, and its therapeutic effects have been well-established. Therefore, patients with moderate to severe allergic rhinitis who do not respond well to currently advised treatments may benefit from anti-IgE therapy with omalizumab. Omalizumab has not yet been approved for the treatment of allergic rhinitis, and because of its high cost, access to it may be restricted [1]–[4].
Dupilumab in the treatment of allergic rhinitis
Dupilumab is an anti-IL-4 monoclonal antibody that inhibits a shared receptor for IL-4 and IL-13, two essential mediators of type 2 inflammation that are crucial in allergic rhinitis. It has been reported that dupilumab can reduce:
Nasal symptoms associated with allergic rhinitis
Type 2 inflammatory markers such as total serum IgE, fractional exhaled nitric oxide (FeNO), and thymus-and activation-regulated chemokine (TARC)
Dupilumab (anti-IL-4Rα) has recently been studied both alone and in combination with allergen-specific immunotherapy to investigate its effects on allergic rhinitis. In asthma patients with perennial allergic rhinitis, dupilumab has been demonstrated to be beneficial in reducing nasal symptoms related to allergic rhinitis. Although encouraging, these findings must be verified in additional research to determine the efficacy, safety, and cost-effectiveness of dupilumab for the treatment of allergic rhinitis. In the treatment of moderate-to-severe allergic diseases, dupilumab is approved by the United States FDA for adult patients:
Whose condition is not well managed with topical prescription medications
When available therapies are not recommended or not effective
The European Medicines Agency (EMA) has also authorized the use of dupilumab in people with moderate-to-severe allergic disorders who can be suitable for systemic therapy. Treatment with a selective immunomodulator like dupilumab would enable systemic therapy with the potential to cure numerous allergy diseases that frequently coexist [1], [2], [5].
Viewpoint on biologics
Although biologics have considerably improved the lives of many patients with allergic diseases and revolutionized treatment options, they have adverse effect profiles that may restrict their tolerance. Biologics have been thought to be an adjuvant therapy in conjunction with allergen-specific immunotherapy to reduce the adverse effects and improve efficacy. Therefore, the therapeutic use of biologics holds the promise of advancing the delivery of customized care to all patients with uncontrolled allergic diseases of which allergic rhinitis is prominent.
References
A. Licari et al., “Current and emerging biologic therapies for allergic rhinitis and chronic rhinosinusitis,” Expert Opin Biol Ther, vol. 20, no. 6, pp. 609–619, Jun. 2020, DOI: 10.1080/14712598.2020.1729350.
Y. Meng, C. Wang, and L. Zhang, “Advances and novel developments in allergic rhinitis,” Allergy, vol. 75, no. 12, pp. 3069–3076, Dec. 2020, doi: 10.1111/all.14586.
C. Damask and C. Franzese, “Mechanisms and Practical Use of Biologic Therapies for Allergy and Asthma Indications,” Otolaryngol Clin North Am, vol. 54, no. 4, pp. 717–728, Aug. 2021, DOI: 10.1016/j.otc.2021.04.003.
T. Ma, H. Wang, and X. Wang, “Effectiveness and Response Predictors of Omalizumab in Treating Patients with Seasonal Allergic Rhinitis: A Real-World Study,” J Asthma Allergy, vol. 14, pp. 59–66, 2021, DOI: 10.2147/JAA.S288952.
S. F. Weinstein et al., “Efficacy and safety of dupilumab in perennial allergic rhinitis and comorbid asthma,” J Allergy Clin Immunol, vol. 142, no. 1, pp. 171-177.e1, Jul. 2018, doi: 10.1016/j.jaci.2017.11.051.
