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

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.