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Wise et al.

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significant differences in efficacy between available agents have been demonstrated in studied populations 1273 ; therefore, sensory attributes may be an important factor in patient preference and adherence to therapy. 1277 These sensory attributes include aftertaste, nose runout, throat rundown, and smell. Addressing some of these concerns are 2 intranasal non aqueous preparations with hydrofluoroalkane (HFA) aerosols recently approved for the treatment of AR in the United States. These include beclomethasone dipropionate and ciclesonide, both approved and effective for SAR and PAR in adults and children 12 years and older. 688,1278-1281 Onset of action for INCS starts at time points ranging from 3 to 5 hours to 60 hours after first dosing. 1282-1285 Although the recommended continuous daily use of INCS is superior to other dosing strategies, 1286,1287 studies have demonstrated the efficacy of as-needed use of intranasal fluticasone propionate compared to placebo 1288,1289 (Table IX.B.2.c-1). Along with improved nasal symptoms, INCSs have beneficial effects on allergic eye symptoms including itching, tearing, redness, and puffiness. 1290-1292 This is secondary to a reduction in the naso-ocular reflex, which contributes to these eye symptoms. 1293 Most INCSs lead to improved ocular symptoms, but the evidence suggests that the effects are not equal among INCS preparations. 1294 Some studies have suggested that INCSs improve asthma control measures in patients suffering from both AR and asthma 1295,1296 (Table IX.B.2.c-2). In comparative studies, INCSs have shown superior efficacy to H 1 antihistamines in controlling nasal symptoms, including nasal congestion, with no significant difference in the relief of ocular symptoms. 1297-1299 INCSs are more effective than LTRAs 1299,1300 (Table IX.B.2.c-3). The most common side effects of INCSs are a result of local irritation and include dryness, burning, stinging, blood-tinged secretions, and epistaxis. The incidence of epistaxis with different preparations ranges from 4% to 8% over short treatment periods (2 to 12 weeks) with no differences between placebo and active therapy. 1301,1302 In studies carried over 1 year, epistaxis is as high as 20%. 1303,1304 Septal perforations are rare complications of INCS. 51 A systematic review of published articles looking at biopsy studies in patients with AR or CRS using INCS identified 34 studies. Of those, 21 studies included patients with AR, mixed rhinitis, and NAR, and 13 involved patients with CRS with/without polyposis. 1305 None of the studies that included atrophy of the nasal mucosa as an outcome measure reported any atrophy with INCS. A meta-analysis of a subgroup of the studies showed no significant chance of developing atrophy while taking INCS, and no difference between active and control groups in basement membrane characteristics. The review also found a significant reduction in the OR for the development of squamous metaplasia in patients using INCS, suggesting a favorable effect. Studies in adults and children evaluating effects of INCS on the hypothalamic pituitary axis have assessed morning cortisol concentrations, cosyntropin stimulation, 24-hour serum cortisol and 24-hour urinary free cortisol excretion. They show no adverse effects. 1304,1306-1317 Although there has been a report of an association between the use of INCS and the development of posterior subcapsular cataracts, 1318 a systematic review of controlled trials did not demonstrate a clinically relevant impact of INCS on either ocular pressure, glaucoma, lens opacity, or cataract formation. 1319 The

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