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Wise et al.

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omalizumab 1402,1736 (Table IX.D.8VIII.E.4.a-1VIII.E.4.a-2). Massanari et al. 1736 evaluated 248 patients with moderate persistent asthma receiving omalizumab pretreatment or placebo prior to cluster AIT, an accelerated AIT buildup schedule. A significantly lower incidence of systemic and respiratory-related reactions was reported among the omalizumab group, with an improved likelihood of reaching maintenance therapy compared to the group without preventive treatment with this biological. Casale et al. 1402 evaluated 123 adult patients with ragweed-induced AR receiving omalizumab prior to 1-day rush AIT, finding a 5-fold decreased risk of systemic allergic reactions with omalizumab pretreatment (OR, 0.17). Further outcomes included significant improvement in daily symptom scores among patients receiving combination therapy (continued omalizumab + AIT) vs AIT alone. Additional study of AIT for the treatment of food 1739 or insect venom 1740,1741 hypersensitivity has also demonstrated improved safety with omalizumab pretreatment. The efficacy of combination therapy for the treatment of AR has been further evaluated by several iterative analyses of a single RCT. 1400,1401,1735 Kuehr et al. 1400 evaluated 221 adolescents (6 to 17 years) with moderate to severe AR and sensitization to birch and grass pollen. Using a randomized, controlled design, the effectiveness of combination therapy was evaluated during sequential birch and grass pollen seasons, with comparison of AIT +/− concurrent omalizumab. Significant findings included superiority of combination therapies vs AIT alone, with 48% reduction in symptom load (sum of mean daily symptom severity score plus mean daily rescue medication use) during an entire pollen season and 80% reduction in median rescue medication score. Two additional studies report unique findings generated by this trial. 1401,1735 Rolinck-Werninghaus et al. 1401 completed a subgroup analysis of study patients receiving specific AIT +/− concurrent omalizumab during the matched grass season. Results included decreased symptoms scores and rescue medication usage for patients receiving combination vs either therapy alone. Kopp et al. 1735 evaluated a subgroup of 92 children, with findings of decreased leukotriene (LTC4, LTD4, and LTE4) release among patients receiving combination therapies following in vitro antigen stimulation of collected blood cells. An unrelated study by Klunker et al. 1734 provides further evidence for the efficacy of combination therapy, with in vitro demonstration of inhibition of allergen-specific IgE binding for 42 weeks after discontinuation of combination therapy (vs 30 weeks with omalizumab alone). While a prior study has estimated the cost of omalizumab (1,253 EUR/patient/month) and AIT therapies (425 EUR/patient/year), evaluation of economic and productivity outcomes has not been completed for patients undergoing combination therapy. 1401 Finally, omalizumab has been associated with anaphylactic reactions in 0.09% to 0.2% of patients, with current recommendations to monitor patients for 30 minutes following administration. 1742,1743 • Aggregate Grade of Evidence: B (Level 1b: 4 studies, plus 2 additional iterative analyses of a parent study; Table IX.D.8). • Benefit: Improved safety of accelerated cluster and rush AIT protocols, with decreased symptom and rescue medication scores among a carefully selected population.

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