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Reference: STICS trial (N Engl J Med 2018 Mar 3 early online) (level 2 [mid-level] evidence)
- Ideal management of children who show early signs of loss of asthma control is unclear.
- The STICS trial randomized 254 children taking maintenance inhaled fluticasone for mild-to-moderate asthma to a 7-day quintupled dose of fluticasone at onset of early signs of loss of asthma control vs. continuation of the maintenance dose.
- After a mean follow-up of about 41 weeks, there was no significant difference between groups in the annualized rate of severe asthma exacerbations requiring systemic corticosteroids (0.48 with quintupled dose vs. 0.37 with maintenance dose, rate ratio 1.3, 95% CI 0.8-2.1).
Increasing the dose of inhaled corticosteroids (ICS) may be considered in children aged 6-11 years who have persistent symptoms or exacerbations of asthma despite maintenance therapy with low dose ICS (Global Initiative for Asthma Report 2017) but studies on how to best manage early signs of loss of asthma control to prevent progression to asthma exacerbation are limited. In the recent STICS trial, 444 children with mild-to-moderate asthma and ≥ 1 asthma exacerbation treated with systemic glucocorticoids in the previous year were given maintenance fluticasone propionate 44 mcg, 2 inhalations twice daily during a 4-week run in phase. Of these, 254 children with > 75% adherence to protocol were randomized to a 7-day quintupled dose of fluticasone to be taken at onset of early signs of loss of asthma control vs. continuation of the maintenance dose. Loss of asthma control was defined as use of 2 doses (4 inhalations) of rescue albuterol in 6 hours, use of 3 doses (6 inhalations) of rescue albuterol in 24 hours, or 1 night awakening due to asthma treated with albuterol. Blinding was maintained by the use of two different inhalers in both groups.
The mean follow-up was 40.3 weeks in the quintupled-dose group and 42.5 weeks in the maintenance-dose group. There were 192 episodes of loss of asthma control in 80 children in the quintupled-dose group and 203 episodes in 88 children in the maintenance-dose group. There was no significant difference between groups in the annualized rate of severe asthma exacerbations requiring systemic corticosteroids (0.48 with quintupled dose vs. 0.37 with maintenance dose, rate ratio 1.3, 95% CI 0.8-2.1). There were also no significant differences in symptom burden or albuterol use during an episode of loss of asthma control. The quintupled dose, however, was associated with a nonsignificant decrease in linear growth (0.23 cm per year, p = 0.06).
Management of early signs of loss of asthma control with a quintupled dose of maintenance ICS was not found to reduce the rate of severe asthma exacerbations requiring systemic corticosteroids in children. This finding is consistent with the results of a Cochrane review evaluating doubling the maintenance dose of ICS in children and adolescents (Cochrane Database Syst Rev 2016). The 95% confidence interval for the effect of fluticasone in the STICS trial includes both a 20% reduction and a 110% increase in the rate of exacerbation, indicating the potential for modest benefit or substantially increased risk of harm for this outcome in addition to the possible negative effects on growth. The pre-selection of children highly adherent to the protocol limits the generalizability of these findings. Another recent trial in adults and adolescents ≥ 16 years old suggests that quadrupling the maintenance dose of ICS at signs of worsening asthma may reduce severe exacerbations (N Engl J Med 2018). This suggests that there may be an age-dependent effect, however, it should be noted that the definition of severe asthma exacerbation in the older patients was a composite outcome including use of systemic corticosteroids and an unplanned health care visit for asthma which may contribute to the different findings. The findings of the STICS trial do not support increasing the ICS dose at first signs of loss of asthma control in children with mild-to-moderate asthma.
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