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Wise et al.

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birch, 1723 cat, 1724 and ragweed 1725 sensitivity, without a significant decline in nasal symptoms, improvements in provocation testing, or reductions in medication utilization. Additionally, oral/gastrointestinal allergen administration requires extract concentrations approaching 200 times greater than SCIT, and is associated with adverse gastrointestinal side effects. 1623,1724 However, the efficacy of oral/gastrointestinal immunotherapy has been demonstrated for the treatment of food hypersensitivity, where this approach remains investigational. 1726 Oral mucosal immunotherapy (OMIT) is an alternative form of AIT that is distinctly different from SLIT and oral/gastrointestinal strategies. OMIT utilizes a glycerin based toothpaste vehicle to introduce antigen to high-density antigen processing oral Langerhans cells in the oral vestibular and buccal mucosa. 1727 Theoretical benefits include induction of immune tolerance with lower antigen concentrations, decreased local side effects and higher adherence vs SLIT. 1728 A recently completed pilot study of OMIT vs SLIT identified clinically meaningful improvements in disease-specific QOL measures with a significant rise in specific IgG4 over the first 6 months of treatment. 1729 No adverse events were reported, and there were no significant differences between outcome measures for both treatment arms. 1729 Additional study is needed to define the role of OMIT in the treatment of AR. Local nasal immunotherapy has been established as an effective approach for the treatment of pollen and HDM sensitivity. 1730 However, high rates of local adverse reactions limit patient compliance, with 1 prior study finding that 43.9% of treated children abandoned this treatment option within the first year of therapy. 1731 High-quality studies of inhaled/ intrabronchial immunotherapy for the treatment of AR have not yet been completed, with current studies limited to the treatment of allergic asthma. 1732 In light of these findings, including poor compliance and limited efficacy, oral/gastrointestinal, nasal, and inhaled immunotherapies have limited utility in the current treatment of AR, while OMIT represents an emerging alternative to SCIT and SLIT. IX.D.8. Combination omalizumab and SCIT— In consideration of combination therapy with concurrent biological omalizumab and AIT, each intervention targets different mechanisms in the allergic cascade. AIT desensitizes the body’s response to a specific antigen, with alteration of the Th1/Th2 balance and induction of T-cell anergy. 1623 Omalizumab indiscriminately targets the humoral effector of allergic inflammation, with use of a humanized monoclonal antibody to block unbound IgE. 1623 While both modalities have independently demonstrated efficacy as treatment options, improved strategies are needed, especially in patients with multiple sensitizations. 1733 Two benefits of combination therapy have been described: decreased incidence of AIT associated systemic allergic reactions and improved control of AR symptoms. 1400-1402,1734-1736 Anaphylaxis is a persistent concern with AIT, with incidence of reported systemic reactions as high as 65% following rush protocols. 1737,1738 Omalizumab pretreatment has therefore been evaluated as a strategy to improve AIT tolerance, with positive findings. Two multicenter, randomized, placebo-controlled studies have evaluated the incidence of AIT-induced systemic allergic reactions following pretreatment with

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Int Forum Allergy Rhinol . Author manuscript; available in PMC 2020 June 10.