Step-up Therapy for Children with Uncontrolled Asthma Receiving Inhaled Corticosteroids

Published - Written by Karen Buckley

Figure 2

Evidence to guide step-up therapy for children whose asthma is poorly controlled by low-dose inhaled corticosteroids (ICS) has been lacking. In a crossover study of 182 children, Lemanske et al. attempt to determine which step-up therapy is best, and whether it can be predicted which therapy will induce a better response in a particular child.

For sixteen weeks, patients aged 6 to 17 were assigned to receive either double the dose of ICS, a leukotriene receptor antagonist (LTRA) in addition to the ICS, or a long-acting beta agonist (LABA) in addition to the ICS. Each child received all three therapies. For each child the investigators determined which treatment, if any, gave the best response.

Just over 40% of children had the best response to adding the long-acting beta agonist, but just under 30% had the best response to either inhaled corticosteroids or the leukotriene receptor antagonist. Since the investigators went to the trouble to study all three treatments in each child, their data illustrate the need to closely monitor each child following step up therapy. If one treatment does not work, another should be tried.

“Since any of the three step-up therapies may work in an individual patient, we would base our first choice for a given patient on three things: surety of safety, price, and convenience, in that order,” said editorialists Jeffrey Drazen, editor-in-chief of NEJM, and Erika von Mutius, University Children’s Hospital in Munich, in Choosing Asthma Step-up Care. They noted that, because of safety concerns with LABAs, “our first choice would be either increasing the dose of an inhaled corticosteroid or adding a leukotriene modifier to the therapeutic regimen.”

The concern about the safety of LABAs was embodied in an NEJM Perspective last month, by Drs. Badrul Chowdhury and Gerald Dal Pan of the FDA. They reviewed the evidence linking LABAs to the risk of serious asthma outcomes and concluded that there were unanswered questions about the safety of LABAs in asthma treatment.

Would you be reluctant to prescribe LABA as a step-up therapy because of safety concerns? Will the results of this study influence your decisions regarding step-up therapy in your practice?