Comparative Effectiveness of Step-up Therapies in Children with Asthma Prescribed Inhaled Corticosteroids: A Historical Cohort Study

J Allergy Clin Immunol Pract. 2017 Jul-Aug;5(4):1082-1090.e7. doi: 10.1016/j.jaip.2016.12.028. Epub 2017 Mar 27.


Background: In children with uncontrolled asthma prescribed low-dose inhaled corticosteroids (ICSs), various step-up options are available: fixed-dose combination ICS/long-acting β2-agonist (FDC), increasing ICS dose, or adding leukotriene receptor antagonist (LTRA). However, evidence of their relative effectiveness is limited.

Objective: To compare the effectiveness of step-up treatment to FDC in children with asthma versus increased ICS dose, or LTRA.

Methods: This matched cohort study used UK primary-care databases to study children prescribed their first step-up treatment to FDC, increased ICS dose, or LTRA. A year of baseline data was used for matching and identifying confounders. Outcomes over the following year were examined. The primary outcome was severe exacerbation rate; secondary outcomes included overall asthma control, derived from databases (no asthma-related admissions/hospital attendances/oral corticosteroids or antibiotics prescribed with a respiratory review, and average prescribed salbutamol ≤200 μg/day).

Results: There were 971 matched pairs in the FDC and increased ICS dose cohorts (59% males; mean age, 9.4 years) and 785 in the FDC and LTRA cohorts (60% males; mean age, 9.0 years). Exacerbation rates in the outcome year were similar between FDC and increased ICS (adjusted incidence rate ratio [95% CI], 1.09 [0.75-1.59]) and FDC and LTRA (incidence rate ratio, 1.36 [0.93-2.01]). Increased ICS and LTRA significantly reduced the odds of achieving overall asthma control, compared with FDC (odds ratios [95% CI], 0.52 [0.42-0.64] and 0.53 [0.42-0.66], respectively)-this was driven by reduced short-acting beta-agonist use.

Conclusions: FDC is as effective as increased ICS or LTRA in reducing severe exacerbation rate, but more effective in achieving asthma control.

Keywords: Asthma; Child; Inhaled corticosteroid; Leukotriene receptor antagonist; Long-acting beta-agonist; Step-up therapy.

Publication types

  • Comparative Study

MeSH terms

  • Administration, Inhalation
  • Adrenal Cortex Hormones / therapeutic use*
  • Adrenergic beta-2 Receptor Agonists / therapeutic use*
  • Anti-Asthmatic Agents / therapeutic use*
  • Asthma / drug therapy*
  • Child
  • Cohort Studies
  • Female
  • Humans
  • Leukotriene Antagonists / therapeutic use*
  • Male


  • Adrenal Cortex Hormones
  • Adrenergic beta-2 Receptor Agonists
  • Anti-Asthmatic Agents
  • Leukotriene Antagonists