Increased inhaled glucocorticoids do not prevent asthma exacerbations in children: The STICS trial

1. In children age 5 to 11 with mild-to-moderate persistent asthma treated with daily inhaled glucocorticoids, quintupling the dose of inhaled glucocorticoids during the initial signs of worsening asthma control did not reduce the rate of severe exacerbations.

2. There was a small but significant decrease in linear growth in children 5 to 7 treated with high-dose inhaled glucocorticoids compared to those in the low-dose group.

Evidence Rating Level: 1 (Excellent)     

Study Rundown: The “yellow zone” of asthma control is used to describe an acute loss of symptom control, during which physicians often increase inhaled glucocorticoid dosage to prevent a costly and potentially dangerous acute exacerbation. However, this common practice has little supporting evidence. The Step Up Yellow Zone Inhaled Corticosteroids to Prevent Exacerbations (STICS) trial aimed to assess the efficacy and safety of a quintupled dose of inhaled glucocorticoids in children with mild-to-moderate persistent asthma experiencing acute loss of asthma control. The results demonstrated no significant difference in the primary outcome – the rate of severe asthma exacerbations treated with systemic glucocorticoids – between the high-dose and low-dose inhaled glucocorticoid groups. There was also no significant difference in the key secondary outcomes of time to first asthma exacerbation, treatment failure, and unscheduled emergency department visits or hospitalizations for asthma. Unexpectedly, children age 5 to 7 in the high-dose group experienced a significant decrease in growth rate compared to those in the low-dose group.

This was a randomized, double-blinded, parallel group trial that studied a cohort of children with previously little data regarding increasing steroid doses for asthma exacerbation prevention. The study’s single population limits generalizability of results, however, as neither children with asthma who do not take inhaled glucocorticoids regularly nor adults were included. These results suggest large doses of inhaled steroids aren’t associated with a benefit in pediatric asthma control and may stunt growth in certain age groups.

Click to read the study, published in NEJM

Relevant Reading: Increased versus stable doses of inhaled corticosteroids for exacerbations of chronic asthma in adults and children

In-Depth [randomized controlled trial]: This double-blind, parallel group trial studied 254 children age 5 to 11 with mild-to-moderate persistent asthma treated with daily low-dose inhaled glucocorticoids. Participants were randomized in a 1:1 ratio to either low-dose (44 mg, n = 127) or high-dose (220 mg, n = 127) fluticasone for 7 days at the early signs of loss of asthma control. The primary outcome was the rate of severe asthma exacerbations treated with systemic glucocorticoids. Notable secondary outcomes included the time to first asthma exacerbation, treatment failure, unscheduled emergency department or hospitalizations for asthma, and linear growth.

One severe asthma exacerbation treated with systemic glucocorticoids occurred in 38 children in the high-dose group (rate, 0.48 per year; 95% confidence interval [CI], 0.33 to 0.70) versus 30 in the low-dose group (rate, 0.37; 95% CI, 0.25 to 0.55) (relative rate [RR], 1.3; 95% CI, 0.8 to 2.1; p = 0.30). There was no significant differences between groups time to the first severe asthma exacerbation (p = 0.20), emergency department visits (RR, 1.3; 95% CI, 0.8 to 2.4; p = 0.30), or rate of treatment failure (RR, 1.3; p = 0.70). Four hospitalizations occurred in the high-dose group versus zero in the low-dose group; however, the between-group difference was not significant (p = 0.12). The growth rate among children in the high-dose group was 0.23 cm/year less than those in the low-dose group (p = 0.06), and growth rate was significantly lower in children between 5 and 8 high-dose treated patients (0.12 cm/year lower growth per yellow-zone episode, p = 0.02 for comparison with low-dose group). There were no significant differences in patient-reported adverse events between the groups.

Image: PD

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