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Wise et al.

Page 115

The minimum age of subjects in most included studies was 12 years or older. Study duration was 14 days of active treatment in most studies, except 1 study with a 3-month duration 1495 and 1 study with a 52-week duration. 1488 The number of subjects in each study ranged from 47 to 3398. Combination therapy with AzeFlu was compared to placebo in 6 studies, with primary outcomes showing superiority to placebo in all studies. 1486,1487,1489-1492 AzeFlu was compared to active treatment with fluticasone propionate monotherapy in 6 studies, all of which showed superiority of the combination therapy. 1488-1490,1492,1494,1495 Similarly, intranasal AzeFlu was compared to active treatment with azelastine hydrochloride monotherapy in 4 studies, all of which showed superiority of the combination therapy. 1489,1490,1492,1494 AzeFlu was directly compared to combination therapy with intranasal olopatadine and fluticasone in 1 study, with no significant difference in symptom relief between treatment groups. 1493 One study found superiority of an experimental combination of solubilized azelastine and budesonide compared to either a suspension-type formulation of azelastine and budesonide or placebo. 1491 Two studies evaluated children aged between 6 and 12 years old. Like findings in adults, AzeFlu showed superiority to placebo in improving symptoms and QOL in children. 1486,1495 Several studies reporting time to onset found that AzeFlu had a more rapid effect compared to INCS alone. Serious adverse effects were not reported in any study. Intranasal antihistamine and corticosteroid combination therapy was generally well tolerated, with the most commonly reported adverse effect being an unpleasant taste. Other reported adverse effects included somnolence, headache, epistaxis, and nasal discomfort, all occurring in less than 5% of cases in each study. One study that compared combination therapy of fluticasone propionate with either azelastine or olopatadine reported more treatment-related events for the azelastine group (16/68) than the olopatadine group (7/67). 1493 • Aggregate Grade of Evidence: A (Level 1b: 9 studies; Level 2b: 1 study; Level 2c: 2 studies; TableIX.B.10.d). • Benefit: Rapid onset, more effective for relief of multiple symptoms than either INCS or intranasal antihistamine alone. • Harm: Patient intolerance, especially due to taste. • Costs: Moderate financial burden. Average wholesale price of $202 USD per 23 g bottle (1-month supply when used as labeled). • Benefits-Harm Assessment: Preponderance of benefit over harm. Combination therapy with intranasal antihistamine and INCS is consistently more effective than placebo. Low risk of non-serious adverse effects. • Value Judgments: Despite level 1 evidence demonstrating that combination spray therapy (INCS plus intranasal antihistamine) is more effective than monotherapy and placebo, the increased financial cost and need for prescription limit the value of combination therapy as a routine first-line treatment for AR. • Policy Level: Strong recommendation for the treatment of AR when monotherapy fails to control symptoms.

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