Contemporary Pharmacotherapy for Allergic Rhinitis and Chronic Rhinosinusitis

Abstract

Chronic rhinosinusitis (CRS) and allergic rhinitis (AR) are chronic conditions causing nasal inflammation. CRS is increasingly recognized as a chronic inflammatory process rather than a chronic infection. It is clinically classified based on the presence of nasal polyps into CRS with nasal polyps (CRSwNP) and CRS without nasal polyps (CRSsNP). While the primary initiating factors in CRS remain unclear, AR is driven by IgE mediated hypersensitivity to environmental allergens. Understanding the underlying inflammatory pathways and disease endotypes are driving innovation toward novel pharmacotherapies targeting critical mediators implicated in CRS and AR including IL-4, IL-13, IL-5, IgE, epithelial initiators IL-33 and TSLP. Many of these new agents have shown promise in RCTs or are being investigated in ongoing RCTs although none have approval for AR or CRS indications yet. Extensive investigations are still needed to determine the role, timing, predictive prognostic factors and long-term safety and efficacy of these agents.

The use of biologics in children with allergic rhinitis and chronic rhinosinusitis: Current updates

“…Patients treated with omalizumab reportedly exhibited significant improvements in both asthma and rhinitis quality of life questionnaire scores . The administration of omalizumab in patients with seasonal AR (SAR) and perennial AR (PAR) has been shown to improve daily nasal symptoms, and quality of life, and reduce IgE levels and the use of rescue antihistamines . In clinical practice, omalizumab has been shown to reduce asthma exacerbations and steroid requirement in allergic asthmatics .…”

“…In that same study it also improved both olfactory and disease‐specific quality of life questionnaire scores, more so than mometasone spray alone . Siglec‐8, a new biologic agent which acts on a receptor found in mature eosinophils is under investigations . The binding of antibody by siglec‐8 will induce apoptosis cytokine‐activated eosinophils and prevention of release of mediators from mast cell …”

“…Different biologics function via a variety of different mechanisms (Figure ). The anti‐IgE monoclonal antibody omalizumab binds to high‐affinity IgE Fc receptor in interstitial fluid and blood, thus blocking the IgE‐mediated inflammatory cascade and eventually reducing the concentration of free IgE in serum which in turn results in reduced binding of IgE to mast cells and basophils . The IL‐5 pathway functions by activating Th2 cells, leading to the release of IL‐5, which in turn leads to increased IgE, eosinophilia, chemotaxis, differentiation, activation, and eosinophil survival .…”

“…The anti‐IgE monoclonal antibody omalizumab binds to high‐affinity IgE Fc receptor in interstitial fluid and blood, thus blocking the IgE‐mediated inflammatory cascade and eventually reducing the concentration of free IgE in serum which in turn results in reduced binding of IgE to mast cells and basophils . The IL‐5 pathway functions by activating Th2 cells, leading to the release of IL‐5, which in turn leads to increased IgE, eosinophilia, chemotaxis, differentiation, activation, and eosinophil survival . In the IL‐4/IL‐13 pathways inhibitors activate cytokines that lead to Th2 cell differentiation and activate a type 2 inflammatory response via IgE synthesis and eosinophils, basophils, and mast cell production .…”

“…Anaphylaxis and hypersensitivity reactions have been reported in 1% of patients . It is recommended that patients undergo an observation period in the clinic after administration, and patients should be informed about the signs and symptoms of anaphylaxis and issued with an epinephrine auto‐injector . Current recommendations include monitoring patients for 2 hours after each of the first 3 three doses, and a 30‐minute observation period after the administration of every subsequent doses .…”