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Wise et al.

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• Benefits-Harm Assessment: Preponderance of benefit over harm. Intranasal antihistamine as monotherapy is consistently more effective than placebo. Most studies show intranasal antihistamines superior to INCS for sneezing, itching, rhinorrhea, and ocular symptoms. Adverse effects are minor and infrequent. • Value Judgments: Extensive level 1 evidence comparing intranasal antihistamine monotherapy to active and placebo controls demonstrates overall effectiveness and safety. • Policy Level: Recommendation. • Intervention: Intranasal antihistamines may be used as first-line or second-line therapy in the treatment of AR. IX.B.2. Corticosteroids IX.B.2.a. Oral corticosteroids.: The anti-inflammatory effect of oral corticosteroids in AR is well known and has been demonstrated experimentally using the nasal challenge model and clinically in the context of seasonal disease. Compared to placebo, premedication with oral prednisone for 2 days prior to an allergen challenge showed a reduction in sneezes, and levels of histamine and mediators of vascular permeability in nasal lavages during the late phase response 884 (Table IX.B.2.a). Further, active treatment resulted in a reduction in the priming response to consecutive allergen challenge. 884 Prednisone has also been shown to reduce the influx of eosinophils and levels of the eosinophil mediators (major basic protein and eosinophil derived neurotoxin) into nasal secretions during the late-phase response compared to placebo. 1242,1243 Non–placebo-controlled studies have demonstrated efficacy of oral corticosteroids for SAR. Schwartz et al. 1244 demonstrated that 15 days of cortisone 25 mg 4 times daily during the ragweed season resulted in significant relief of symptoms in 21 of 25 patients. Similarly, 100 mg of cortisone daily for 4-day courses during the pollen season showed rhinitis symptom relief in 42 of 51 patients, with 20 patients relapsing within 7 days after cessation of therapy. 1245 Oral hydrocortisone 40 to 80 mg daily has also been shown to reduce symptoms of ragweed allergies. 1246 Brooks et al. 1247 performed a placebo-controlled study comparing the efficacy of methylprednisolone 6, 12, or 24 mg PO daily for 5 days to placebo in controlling nasal symptoms during the ragweed season. Whereas the 6-mg and 12-mg doses led to a significant reduction in some of the symptoms compared to placebo (congestion, postnasal drainage, and eye symptoms), the 24 mg dose resulted in a significant reduction of all symptoms (congestion, runny nose, sneezing, itching, postnasal drainage, and eye symptoms). Because of the recognized systemic adverse events associated with oral corticosteroids, 101 their use has been largely replaced by the intranasal preparations. In a double-blind, placebo controlled trial, the effect of intranasal flunisolide and its oral dose bioequivalent (an oral dose that would lead to similar systemic levels) were compared in ragweed-induced SAR. 1248 The intranasal preparation was shown to be efficacious in reducing rhinitis symptoms while the oral dosing was not. This suggested that INCSs achieve their benefit primarily by their local activity as opposed to systemic bioavailability. In a head-to-head comparison of the efficacy of intranasal vs systemic steroids, Karaki et al. 1249 performed an open-label, parallel, randomized trial during the cedar pollen season in Japan. Patients received

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