MADISON, USA – What are a primary care physician’s options when a treatment with twice-daily inhaled corticosteroids fails to control asthma symptoms? A new study has attempted to answer this question for children 6 to 17 years of age.

Uncontrolled asthma frequently occurs in children, despite treatment with low-dose inhaled corticosteroids. The evidence to guide step-up therapy for such children is scarce and inconsistent.
A team of American researchers of the University of Wisconsin School of Medicine and Public Health sought to find the best approach for these children. They conducted a multicentre study in which they enrolled 182 children who, despite receiving treatment with 100 µg of inhaled fluticasone twice daily, still suffered from mild-to-moderate asthma.
They assigned the patients to receive three different blinded step-up strategies in random order for 16 weeks: an increase of the corticosteroid dose to 250 µg of fluticasone twice daily (ICS step-up); 100 µg of fluticasone and an additional long-acting beta-2-agonist (50 µg salmeterol) 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).

Each child received all three therapies, and treatment success was determined on an individual basis.
During each treatment period, the researchers looked at the responses to the various step-up regimens – in terms of number of exacerbations requiring oral prednisone, asthma-control days, and lung function.
At the completion of treatment, the investigators ranked the step-up therapies in each child on the basis of these outcomes and categorised the child as either having a differential response to step-up treatment (and if so, which therapy provided the best response) or not having a differential response.
A differential response occurred in 161 of 165 patients (98%).
LABA step-up therapy was significantly more likely than the other step-up treatments to give the best response, as compared with responses to either of the two other regimens (LTRA step-up and ICS step-up).
The probability for a best response was about 45% for LABA step-up, and just under 30% for either LTRA or ICS step-up.

For the most part, baseline characteristics did not predict the therapy most likely to be best for an individual patient. However, higher scores on the Asthma Control Test before randomisation (indicating better control at baseline) predicted a better response to LABA step-up.
From a clinician’s perspective, the authors emphasise the need to regularly monitor and appropriately adjust each child’s asthma therapy given the fact that there were still many children who had a best response to ICS or LTRA step-up therapy.

“Our data show that to achieve improvements in asthma control, the addition of a different class of medication is often required,” the authors emphasise.

Although LABA step-up therapy was most likely to provide the best response, some children had a best response to one of the other step-up therapies. Also, clinicians who prescribe LABAs (“never to be used as monotherapy”) in combination with inhaled corticosteroids should continue to evaluate risk–benefit ratios and observe the long-term safety issues of LABA in children, as urged by the FDA.

From a researcher’s perspective, the authors suggest that evidence from comparison studies is needed, in order to establish which step-up therapy is best and whether there are phenotypic or genotypic characteristics that can be used to predict whether a child will have a better response to one particular step-up treatment than to another.

“Despite step-up in daily therapy, 120 exacerbations requiring the use of oral corticosteroids occurred during the treatment periods. Day-to-day asthma control, as reflected by the number of asthma-control days, was quite good with all three step-up therapies. However, none of the step-up therapies completely prevented asthma exacerbations. These findings underscore the need for new therapies aimed at preventing exacerbations,” the authors conclude.

Reference:
Lemanske RF et al. N Engl J Med. 2010 Mar 18;362(11):975-85