Long-acting β--agonists best option for “step-up” therapy for children with uncontrolled asthma
Article Outline
- Question
- Design
- Setting
- Participants
- Intervention
- Outcomes
- Main Results
- Conclusions
- Commentary
- References
- Copyright
Lemanske RJ, Mauger D, Sorkness C, Jackson D, Boehmer S, Martinez F, et al. Step-up therapy for children with uncontrolled asthma receiving inhaled corticosteroids. N Engl J Med 2010;362:975-85.
Question
Among children who have uncontrolled asthma despite the use of low-dose inhaled corticosteroids (ICS), what is the best option for “step-up” therapy?
Design
Randomized, blinded, multicenter study.
Setting
Childhood Asthma Research and Education (CARE) Network sites.
Participants
One hundred eighty-two children (6 to 17 years of age) who had uncontrolled asthma while receiving 100 μg of fluticasone twice daily.
Intervention
Each participant received three blinded step-up therapies in random order for 16 weeks: 250 μg of fluticasone twice daily (ICS step-up), 100 μg of fluticasone plus 50 μg of a long-acting β-agonist twice daily (LABA step-up), or 100 μg of fluticasone twice daily plus 5 or 10 mg of a leukotriene-receptor antagonist daily (LTRA step-up).
Outcomes
A differential response for a composite of three outcomes (exacerbations, asthma-control days, and the forced expiratory volume in 1 second).
Main Results
A differential response occurred in 161 of 165 patients who were evaluated (P < .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 = .004) and ICS step-up (relative probability, 1.7; 95% CI, 1.2 to 2.4; P = .002). Higher scores on the Asthma Control Test before randomization (indicating better control at baseline) predicted a better response to LABA step-up (P = .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 = .005).
Conclusions
Nearly all the children in this study 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.
Commentary
Using current asthma clinical practice guidelines, clinicians have several choices for step-up therapy for children with uncontrolled asthma who are already on ICS. This study compares the effectiveness of several strategies: step-up ICS therapy, adding an LABA, or adding an LTRA. In this study, although there were groups of children that responded to all three step-up strategies (ICS, LABA or LTRA), LABA step-up therapy was significantly more likely to provide the best response compared with LTRA (relative probability, 1.6; 95% CI, 1.1 to 2.3) and ICS step-up (relative probability, 1.7; 95% CI, 1.2 to 2.4). Post hoc analyses suggest that patient characteristics may also be helpful in guiding therapy. African-Americans were equally likely to respond best to ICS step-up or LABA, and Hispanic and non-Hispanic white patients were likely to respond best to LABA. This study fills in key gaps for initial step-up therapy in current guidelines but also reminds clinicians that therapy eventually must be individualized. In this study, the adherence rate for study medications was well over 80%. This adherence rate probably is higher than what most clinicians experience in daily practice.1 In many clinical scenarios, current therapy may be appropriate, but patient adherence may be poor. In addition, the more complicated the medical regimen, the lower the likelihood of patient adherence.2 As a result, it is important to consider, investigate, and address poor patient adherence to existing therapy before considering step-up therapy.
References
PII: S0022-3476(10)00593-7
doi:10.1016/j.jpeds.2010.07.015
© 2010 Mosby, Inc. All rights reserved.
