Step-up therapy for children with uncontrolled asthma receiving inhaled corticosteroids

N Engl J Med. 2010 Mar 18;362(11):975-85. doi: 10.1056/NEJMoa1001278. Epub 2010 Mar 2.

Abstract

Background: For children who have uncontrolled asthma despite the use of low-dose inhaled corticosteroids (ICS), evidence to guide step-up therapy is lacking.

Methods: We randomly assigned 182 children (6 to 17 years of age), who had uncontrolled asthma while receiving 100 microg of fluticasone twice daily, to receive each of three blinded step-up therapies in random order for 16 weeks: 250 microg of fluticasone twice daily (ICS step-up), 100 microg of fluticasone plus 50 microg of a long-acting beta-agonist twice daily (LABA step-up), or 100 microg of fluticasone twice daily plus 5 or 10 mg of a leukotriene-receptor antagonist daily (LTRA step-up). We used a triple-crossover design and a composite of three outcomes (exacerbations, asthma-control days, and the forced expiratory volume in 1 second) to determine whether the frequency of a differential response to the step-up regimens was more than 25%.

Results: A differential response occurred in 161 of 165 patients who were evaluated (P<0.001). The response to LABA step-up therapy was most likely to be the best response, as compared with responses to LTRA step-up (relative probability, 1.6; 95% confidence interval [CI], 1.1 to 2.3; P=0.004) and ICS step-up (relative probability, 1.7; 95% CI, 1.2 to 2.4; P=0.002). Higher scores on the Asthma Control Test before randomization (indicating better control at baseline) predicted a better response to LABA step-up (P=0.009). White race predicted a better response to LABA step-up, whereas black patients were least likely to have a best response to LTRA step-up (P=0.005).

Conclusions: Nearly all the children had a differential response to each step-up therapy. LABA step-up was significantly more likely to provide the best response than either ICS or LTRA step-up. However, many children had a best response to ICS or LTRA step-up therapy, highlighting the need to regularly monitor and appropriately adjust each child's asthma therapy. (ClinicalTrials.gov number, NCT00395304.)

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Acetates / administration & dosage*
  • Administration, Inhalation
  • Administration, Oral
  • Adolescent
  • Adrenergic beta-Agonists / administration & dosage
  • Albuterol / administration & dosage
  • Albuterol / analogs & derivatives*
  • Androstadienes / administration & dosage*
  • Asthma / complications
  • Asthma / drug therapy*
  • Asthma / ethnology
  • Asthma / physiopathology
  • Bronchodilator Agents / administration & dosage*
  • Bronchodilator Agents / adverse effects
  • Child
  • Cross-Over Studies
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Drug Therapy, Combination
  • Eczema / complications
  • Female
  • Fluticasone
  • Forced Expiratory Volume / drug effects
  • Glucocorticoids / administration & dosage
  • Humans
  • Leukotriene Antagonists / administration & dosage
  • Logistic Models
  • Male
  • Prednisone / administration & dosage
  • Quinolines / administration & dosage*
  • Salmeterol Xinafoate
  • Treatment Outcome

Substances

  • Acetates
  • Adrenergic beta-Agonists
  • Androstadienes
  • Bronchodilator Agents
  • Glucocorticoids
  • Leukotriene Antagonists
  • Quinolines
  • Salmeterol Xinafoate
  • Fluticasone
  • montelukast
  • Albuterol
  • Prednisone

Associated data

  • ClinicalTrials.gov/NCT00395304

Grant support