Clinical Year in Review III

Abstract

A significant proportion of children with asthma who are treated with low-dose inhaled corticosteroids (ICS) continue to experience suboptimal disease control and exacerbations. Despite this, the best approach for escalating therapy in these children remains unclear. In the BADGER (Best Add-On Therapy Giving Effective Responses) trial (1), Lemanske and colleagues assessed therapeutic response to three different strategies of escalating therapy beyond low-dose ICS: (1) increasing the dose of the ICS from 100 mg twice daily to 250 mg twice daily; (2) adding montelukast, either 5 or 10 mg daily, to fluticasone, 100 mg twice daily; or (3) adding salmeterol, 50 mg twice daily, to fluticasone, 100 mg twice daily. These strategies were compared in a three-way crossover trial with the primary outcome being a composite of asthma exacerbations, asthma control days, and FEV1. Subjects had mild or moderate persistent asthma according to guidelines, and were eligible to proceed to randomization if they had symptoms 2 days per week on average during a 2-week period, utilized a rescue bronchodilator greater than or equal to 2 puffs/day, or had peak flows less than 80% of predicted during treatment with fluticasone (100 mg twice daily). After 16 weeks of treatment, 98% of participants demonstrated differential response to the three treatment strategies, with the greatest proportion of children responding most favorably to the addition of the long-acting b-agonist. The authors investigated predictors of favorable response to the various regimens, and found that an Asthma Control Test score greater than 19 predicted a favorable response to the addition of the longacting b-agonist. White race also predicted better responsiveness to the addition of the long-acting b-agonist, with black race being associated with a lower likelihood of a favorable response to leukotriene receptor antagonist and equivalent response to long-acting b-agonist or and inhaled steroid increase. The authors concluded that almost all participants demonstrated differential response to the three escalation strategies, with longacting b-agonist add-on therapy significantly more likely to provide the best response when compared with either increasing the dose of inhaled steroid or adding a leukotriene receptor antagonist. Nevertheless, approximately 25% of participants demonstrated a best response to either increasing the dose of inhaled steroid or adding a leukotriene receptor antagonist, suggesting that a substantial minority of patients may do as well or better with step-up therapies other than the addition of a long-acting b-agonist.