Step-Up With LABAs Controlled Asthma Best

NEW ORLEANS — About 98% of children with uncontrolled asthma experienced clinically significant improvements on each of three types of step-up therapy, but treatment with long-acting beta-agonists yielded significantly better responses, according to a new study.

“Step-up with long-acting beta-agonists was more than one and a half times more likely to produce the best response,” Dr. Robert F. Lemanske Jr. said at the annual meeting of the American Academy of Allergy, Asthma, and Immunology. The results were presented at the meeting and published online in the New England Journal of Medicine.

Asthma treatment with long-acting beta-agonists (LABAs) has come under scrutiny in the wake of recent recommendations from the Food and Drug Administration to step down the use of these drugs in asthmatic children once their asthma is controlled. But few data are available to guide clinicians on the next steps in the treatment of children with asthma who are already using a low-dose inhaled corticosteroid (ICS), said Dr. Lemanske of the University of Wisconsin, Madison. He and his colleagues developed the Best Add-on Therapy Giving Effective Responses (BADGER) trial (N. Engl. J. Med. 2010 March 2 [doi: 10.1056/NEJMoa1001278

“This trial was not intended to look at safety,” Dr. Lemanske emphasized.

In the study, the researchers randomized 182 children aged 6-17 years with uncontrolled mild to moderate asthma to one of three therapies in three 16-week study periods. Every patient received each of the three therapies for 16 weeks. The first 4 weeks of the last two 16-week periods were considered run-in and washout periods. A total of 25 treatment failures occurred, and complete data were available for 157 patients.

The three therapies were ICS step-up therapy, consisting of 250 mcg of fluticasone twice daily; LABA step-up therapy, consisting of 100 mcg of fluticasone plus 50 mcg of salmeterol twice daily; or leukotriene-receptor antagonist therapy (LTRA), consisting of 100 mcg of fluticasone twice daily plus an age-appropriate dose (5 or 10 mg) of montelukast daily.

In pair comparisons, the proportion of children who responded best to LABA was 52% vs. LTRA (34%), and 54% vs. ICS (32%). The differences between LABA and each of the other two protocols were significant, but the differences between LTRA and ICS were not.

Of several primary factors used to predict best response, only a higher baseline score (greater than 19) on the Asthma Control Test or Childhood Asthma Control Test (depending on age) was a significant predictor of best response to the LABA therapy.

Of several secondary predictors, children without eczema were significantly more likely to have a best response to LABA therapy. In addition, race was a significant predictor of response. Black children were equally likely to have a best response to LABA or ICS therapy, and least likely to have a best response to LTRA therapy. Non-Hispanic white children and Hispanic children were most likely to have their best response to LABA therapy.

The findings suggest a ceiling effect beyond which low-dose ICS therapy is not effective, the researchers wrote.

Although the proportion of children who had a best response to LABA was significantly greater than with the other two treatments, “many children demonstrated a best response to either ICS or LTRA step-up therapy, highlighting the need to regularly monitor and appropriately adjust each child's asthma therapy,” Dr. Lemanske said at the meeting.

A total of seven serious adverse events were reported. The most common serious adverse event was asthma exacerbation.

Dr. Lemanske has received consulting fees and grant support from multiple pharmaceutical companies, including MAP Pharmaceuticals Inc., Gray Consulting Inc., Merck & Co., AstraZeneca, and Genentech Inc. The study was funded in part by the National Heart, Lung, and Blood Institute, and the study drugs and matching placebos were supplied by GlaxoSmithKline and Merck.

NEW ORLEANS — About 98% of children with uncontrolled asthma experienced clinically significant improvements on each of three types of step-up therapy, but treatment with long-acting beta-agonists yielded significantly better responses, according to a new study.

“Step-up with long-acting beta-agonists was more than one and a half times more likely to produce the best response,” Dr. Robert F. Lemanske Jr. said at the annual meeting of the American Academy of Allergy, Asthma, and Immunology. The results were presented at the meeting and published online in the New England Journal of Medicine.

Asthma treatment with long-acting beta-agonists (LABAs) has come under scrutiny in the wake of recent recommendations from the Food and Drug Administration to step down the use of these drugs in asthmatic children once their asthma is controlled. But few data are available to guide clinicians on the next steps in the treatment of children with asthma who are already using a low-dose inhaled corticosteroid (ICS), said Dr. Lemanske of the University of Wisconsin, Madison. He and his colleagues developed the Best Add-on Therapy Giving Effective Responses (BADGER) trial (N. Engl. J. Med. 2010 March 2 [doi: 10.1056/NEJMoa1001278

“This trial was not intended to look at safety,” Dr. Lemanske emphasized.

In the study, the researchers randomized 182 children aged 6-17 years with uncontrolled mild to moderate asthma to one of three therapies in three 16-week study periods. Every patient received each of the three therapies for 16 weeks. The first 4 weeks of the last two 16-week periods were considered run-in and washout periods. A total of 25 treatment failures occurred, and complete data were available for 157 patients.

The three therapies were ICS step-up therapy, consisting of 250 mcg of fluticasone twice daily; LABA step-up therapy, consisting of 100 mcg of fluticasone plus 50 mcg of salmeterol twice daily; or leukotriene-receptor antagonist therapy (LTRA), consisting of 100 mcg of fluticasone twice daily plus an age-appropriate dose (5 or 10 mg) of montelukast daily.

In pair comparisons, the proportion of children who responded best to LABA was 52% vs. LTRA (34%), and 54% vs. ICS (32%). The differences between LABA and each of the other two protocols were significant, but the differences between LTRA and ICS were not.

Of several primary factors used to predict best response, only a higher baseline score (greater than 19) on the Asthma Control Test or Childhood Asthma Control Test (depending on age) was a significant predictor of best response to the LABA therapy.

Of several secondary predictors, children without eczema were significantly more likely to have a best response to LABA therapy. In addition, race was a significant predictor of response. Black children were equally likely to have a best response to LABA or ICS therapy, and least likely to have a best response to LTRA therapy. Non-Hispanic white children and Hispanic children were most likely to have their best response to LABA therapy.

The findings suggest a ceiling effect beyond which low-dose ICS therapy is not effective, the researchers wrote.

Although the proportion of children who had a best response to LABA was significantly greater than with the other two treatments, “many children demonstrated a best response to either ICS or LTRA step-up therapy, highlighting the need to regularly monitor and appropriately adjust each child's asthma therapy,” Dr. Lemanske said at the meeting.

A total of seven serious adverse events were reported. The most common serious adverse event was asthma exacerbation.

Dr. Lemanske has received consulting fees and grant support from multiple pharmaceutical companies, including MAP Pharmaceuticals Inc., Gray Consulting Inc., Merck & Co., AstraZeneca, and Genentech Inc. The study was funded in part by the National Heart, Lung, and Blood Institute, and the study drugs and matching placebos were supplied by GlaxoSmithKline and Merck.

NEW ORLEANS — About 98% of children with uncontrolled asthma experienced clinically significant improvements on each of three types of step-up therapy, but treatment with long-acting beta-agonists yielded significantly better responses, according to a new study.

“Step-up with long-acting beta-agonists was more than one and a half times more likely to produce the best response,” Dr. Robert F. Lemanske Jr. said at the annual meeting of the American Academy of Allergy, Asthma, and Immunology. The results were presented at the meeting and published online in the New England Journal of Medicine.

Asthma treatment with long-acting beta-agonists (LABAs) has come under scrutiny in the wake of recent recommendations from the Food and Drug Administration to step down the use of these drugs in asthmatic children once their asthma is controlled. But few data are available to guide clinicians on the next steps in the treatment of children with asthma who are already using a low-dose inhaled corticosteroid (ICS), said Dr. Lemanske of the University of Wisconsin, Madison. He and his colleagues developed the Best Add-on Therapy Giving Effective Responses (BADGER) trial (N. Engl. J. Med. 2010 March 2 [doi: 10.1056/NEJMoa1001278

“This trial was not intended to look at safety,” Dr. Lemanske emphasized.

In the study, the researchers randomized 182 children aged 6-17 years with uncontrolled mild to moderate asthma to one of three therapies in three 16-week study periods. Every patient received each of the three therapies for 16 weeks. The first 4 weeks of the last two 16-week periods were considered run-in and washout periods. A total of 25 treatment failures occurred, and complete data were available for 157 patients.

The three therapies were ICS step-up therapy, consisting of 250 mcg of fluticasone twice daily; LABA step-up therapy, consisting of 100 mcg of fluticasone plus 50 mcg of salmeterol twice daily; or leukotriene-receptor antagonist therapy (LTRA), consisting of 100 mcg of fluticasone twice daily plus an age-appropriate dose (5 or 10 mg) of montelukast daily.

In pair comparisons, the proportion of children who responded best to LABA was 52% vs. LTRA (34%), and 54% vs. ICS (32%). The differences between LABA and each of the other two protocols were significant, but the differences between LTRA and ICS were not.

Of several primary factors used to predict best response, only a higher baseline score (greater than 19) on the Asthma Control Test or Childhood Asthma Control Test (depending on age) was a significant predictor of best response to the LABA therapy.

Of several secondary predictors, children without eczema were significantly more likely to have a best response to LABA therapy. In addition, race was a significant predictor of response. Black children were equally likely to have a best response to LABA or ICS therapy, and least likely to have a best response to LTRA therapy. Non-Hispanic white children and Hispanic children were most likely to have their best response to LABA therapy.

The findings suggest a ceiling effect beyond which low-dose ICS therapy is not effective, the researchers wrote.

Although the proportion of children who had a best response to LABA was significantly greater than with the other two treatments, “many children demonstrated a best response to either ICS or LTRA step-up therapy, highlighting the need to regularly monitor and appropriately adjust each child's asthma therapy,” Dr. Lemanske said at the meeting.

A total of seven serious adverse events were reported. The most common serious adverse event was asthma exacerbation.

Dr. Lemanske has received consulting fees and grant support from multiple pharmaceutical companies, including MAP Pharmaceuticals Inc., Gray Consulting Inc., Merck & Co., AstraZeneca, and Genentech Inc. The study was funded in part by the National Heart, Lung, and Blood Institute, and the study drugs and matching placebos were supplied by GlaxoSmithKline and Merck.