Preseasonal treatment with either omalizumab or an inhaled corticosteroid boost to prevent fall asthma exacerbations

Abstract

Background Short-term targeted treatment can potentially prevent fall asthma exacerbations while limiting therapy exposure. Objective We sought to compare (1) omalizumab with placebo and (2) omalizumab with an inhaled corticosteroid (ICS) boost with regard to fall exacerbation rates when initiated 4 to 6 weeks before return to school. Methods A 3-arm, randomized, double-blind, double placebo-controlled, multicenter clinical trial was conducted among inner-city asthmatic children aged 6 to 17 years with 1 or more recent exacerbations (clincaltrials.gov #NCT01430403). Guidelines-based therapy was continued over a 4- to 9-month run-in phase and a 4-month intervention phase. In a subset the effects of omalizumab on IFN-α responses to rhinovirus in PBMCs were examined. Results Before the falls of 2012 and 2013, 727 children were enrolled, 513 were randomized, and 478 were analyzed. The fall exacerbation rate was significantly lower in the omalizumab versus placebo arms (11.3% vs 21.0%; odds ratio [OR], 0.48; % CI, 0.25–.92), but there was no significant difference between omalizumab and ICS boost (8.4% vs 11.1%; OR, 0.73; 95% CI, 0.33–1.64). In a prespecified subgroup analysis, among participants with an exacerbation during the run-in phase, omalizumab was significantly more efficacious than both placebo (6.4% vs 36.3%; OR, 0.12; 95% CI, 0.02–0.64) and ICS boost (2.0% vs 27.8%; OR, 0.05; 95% CI, 0.002–0.98). Omalizumab improved IFN-α responses to rhinovirus, and within the omalizumab group, greater IFN-α increases were associated with fewer exacerbations (OR, 0.14; 95% CI, 0.01–0.88). Adverse events were rare and similar among arms. Conclusions Adding omalizumab before return to school to ongoing guidelines-based care among inner-city youth reduces fall asthma exacerbations, particularly among those with a recent exacerbation.

Recognition and management of severe asthma: A Canadian Thoracic Society position statement

“…38 A RCT of omalizumab in adolescents included total FeNO as one of eleven pre-specified subgroup analyses and did not find that outcomes differed according to the level of baseline FeNO. 39 Only one trial of anti-IL5 therapy had a pre-specified analysis by FeNO ( 50 ppb); high levels of FeNO did not identify responders to mepolizumab. 41 It should be noted that thresholds used to define elevated eosinophils in asthma clinical trials (e.g.…”

“…54 Recently, cross-linking of IgE has been shown to decrease interferon response to rhinovirus which provides a novel pathophysiologic mechanism for more severe viral-induced asthma exacerbations in atopic children. 39 IgE is reported in IU/ml, ng/ml or mcg/L (1 IU/ml D 2.4 ng/ml…”

“…The summary below includes data from four trials of children with mild to severe asthma. 39,85,95,96 A total of 645 children with severe asthma (National Heart, Lung, and Blood Institute (NHLBI) step 5 or equivalent) were included in the three additional RCTs 39,89,95 involving children 6 to 20 years of age with predominantly moderate to severe asthma. A further publication was a subgroup analysis of individuals with severe asthma from a previous clinical trial.…”

“…A further publication was a subgroup analysis of individuals with severe asthma from a previous clinical trial. 98 Subcutaneous omalizumab decreased exacerbation rates by 50% (0.73 with omalizumab, 1.44 with placebo, (risk ratio (RR) 0.504; 95% CI 0.35-0.725, p < 0.001), 98 decreased the percentage of individuals with at least one exacerbation (32.6% compared to 15.1%, OR 0.37, 95% CI 0.17-0.81) 39 (48.8% compared to 30.3%, ¡18.5 difference (¡28.2 to -8.8) p < 0.001), 95 and decreased hospitalizations (6.3 § 1.8 versus 1.5 § 0.9, difference ¡4.7 (95% CI ¡8.6 to ¡0.9, p 0.02). 95 There were less consistent effects on asthma control 89,99 and on the ability to decrease ICS doses.…”

“…89 Omalizumab was associated with a significant reduction in the rate of seasonal exacerbations, occurring in the fall, in children aged 6-17 years when compared to controls (OR 0.48, 95% CI 0.25-0.92), but there was no significant difference when compared to doubling the dose of ICS. 39 …”