title: Comparative Effectiveness of Step-up Therapies in Children with Asthma Prescribed Inhaled Corticosteroids: A Historical Cohort Study.
abstract: 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.
authors.affiliation: Division of Infection, Immunity and Respiratory Medicine, Manchester Academic Health Science Centre, The University of Manchester, University Hospital of South Manchester, NHS Foundation Trust, Manchester; Royal Manchester Children's Hospital, Central Manchester University Hospitals, NHS Foundation Trust, Manchester, Manchester. Electronic address: Clare.murray@manchester.ac.uk.
authors.forename: Clare S
authors.initials: CS
authors.lastname: Murray
authors.affiliation: Primary Care and Population Sciences, University of Southampton, Southampton; NIHR Southampton Respiratory Biomedical Research Unit, Southampton.
authors.forename: Mike
authors.initials: M
authors.lastname: Thomas
authors.affiliation: Observational and Pragmatic Research Institute Pte Ltd, Singapore.
authors.forename: Kathryn
authors.initials: K
authors.lastname: Richardson
authors.affiliation: Observational and Pragmatic Research Institute Pte Ltd, Singapore; Academic Primary Care, University of Aberdeen, Aberdeen.
authors.forename: David B
authors.initials: DB
authors.lastname: Price
authors.affiliation: Child Health, University of Aberdeen, Aberdeen.
authors.forename: Steve W
authors.initials: SW
authors.lastname: Turner
mesh_terms: D000280:Administration, Inhalation; D000305:Adrenal Cortex Hormones / Q000627:therapeutic use*; D058666:Adrenergic beta-2 Receptor Agonists / Q000627:therapeutic use*; D018927:Anti-Asthmatic Agents / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy*; D002648:Child; D015331:Cohort Studies; D005260:Female; D006801:Humans; D020024:Leukotriene Antagonists / Q000627:therapeutic use*; D008297:Male
chemical_list: D000305:Adrenal Cortex Hormones; D058666:Adrenergic beta-2 Receptor Agonists; D018927:Anti-Asthmatic Agents; D020024:Leukotriene Antagonists
keywords: Asthma; Child; Inhaled corticosteroid; Leukotriene receptor antagonist; Long-acting beta-agonist; Step-up therapy