Step-Down Therapy Feasible for Stabilized Asthma

SAN DIEGO — Once-a-day step-down therapy can be an option for patients with mild, persistent asthma that has been stabilized by an inhaled corticosteroid, according to preliminary results from a 500-patient clinical trial presented at the international conference of the American Thoracic Society.

Dr. Stephen P. Peters said one puff a day of a fluticasone (100 mcg) and salmeterol (50 mcg) combination was as effective as 100 mcg of low-dose fluticasone twice a day. Only 20% of patients on either therapy failed treatment in the 15-week study.

A third group of patients did not fare as well on a pill containing 5 mg or 10 mg of montelukast each day. About 30% of patients failed treatment. Investigators calculated the relative risk of treatment failure as 60% higher than with fluticasone alone or fluticasone/salmeterol. Even so, the patients on montelukast fared well enough that all three regimens are viable, said Dr. Peters, director of research in pulmonary and critical care medicine at Wake Forest University, Winston-Salem, N.C.

“Although twice-a-day inhaled corticosteroid remains the treatment of choice for persistent asthma, alternatives could be considered on a case-by-case basis,” he said, citing the fluticasone/salmeterol combination. “There are still a lot of folks … who also did well, even on montelukast.”

The study, known as the Leukotriene Modifier or Corticosteroid or Corticosteroid-Salmeterol Trial, was sponsored by the American Lung Association's Asthma Clinical Research Centers. An unrestricted grant from GlaxoSmithKline provided financial support.

The trial randomized 168 patients to fluticasone, 162 patients to fluticasone/salmeterol, and 165 patients to montelukast after a phase-in period during which mild asthma was stabilized on an inhaled corticosteroid. Dr. Peters said all patients took a pill and used inhalers without knowing which one of their treatments had an active ingredient and which two were placebo.

The population was evenly divided between men and women and had an average age of 31 years. About 18% of patients were children, and more than a third were African American or Hispanic. As a group, they were longtime asthma patients with an average of 16 years since diagnosis. Dr. Peters characterized the participants as “the group we are used to seeing.”

The trial's primary outcome was time to treatment failure, which the investigators defined in seven ways, including physician judgment. Patients who had treatment failures could have more than one reason for a treatment failure.

There were 50 treatment failures with montelukast, 34 with fluticasone, and 33 with fluticasone/salmeterol. The most common reason was a 20% or greater drop in forced expiratory volume in 1 second (FEV₁), which 48% of patients with treatment failures experienced: 26 patients on montelukast, 16 on the combination, and 14 on single-agent fluticasone.

Three components of asthma exacerbation accounted for a total of 48% of treatment failures: systemic steroids, inhaled corticosteroid use (not counting exercise medication), and urgent care. The proportion of patients with asthma exacerbation was similar: 13% with montelukast, 11% with fluticasone/salmeterol, and 10% with fluticasone alone. The only significant difference was in inhaler use when montelukast was compared with fluticasone/salmeterol (23% vs. 17%).

In other measures, Dr. Peters said montelukast was “slightly inferior” for nocturnal awakenings, prebronchodilator FEV₁, and responses on the Asthma Control Questionnaire. Fluticasone/salmeterol was “slightly superior” for morning peak expiratory flow. He reported no difference in the Asthma Symptom Utility Index, Adult Asthma Quality of Life, serious adverse events, or percentage of symptom-free days (79% vs. 86%). For all three groups, most days were symptom free and rescue inhaler use was infrequent. Adherence is an underlying issue, he said in an interview.

SAN DIEGO — Once-a-day step-down therapy can be an option for patients with mild, persistent asthma that has been stabilized by an inhaled corticosteroid, according to preliminary results from a 500-patient clinical trial presented at the international conference of the American Thoracic Society.

Dr. Stephen P. Peters said one puff a day of a fluticasone (100 mcg) and salmeterol (50 mcg) combination was as effective as 100 mcg of low-dose fluticasone twice a day. Only 20% of patients on either therapy failed treatment in the 15-week study.

A third group of patients did not fare as well on a pill containing 5 mg or 10 mg of montelukast each day. About 30% of patients failed treatment. Investigators calculated the relative risk of treatment failure as 60% higher than with fluticasone alone or fluticasone/salmeterol. Even so, the patients on montelukast fared well enough that all three regimens are viable, said Dr. Peters, director of research in pulmonary and critical care medicine at Wake Forest University, Winston-Salem, N.C.

“Although twice-a-day inhaled corticosteroid remains the treatment of choice for persistent asthma, alternatives could be considered on a case-by-case basis,” he said, citing the fluticasone/salmeterol combination. “There are still a lot of folks … who also did well, even on montelukast.”

The study, known as the Leukotriene Modifier or Corticosteroid or Corticosteroid-Salmeterol Trial, was sponsored by the American Lung Association's Asthma Clinical Research Centers. An unrestricted grant from GlaxoSmithKline provided financial support.

The trial randomized 168 patients to fluticasone, 162 patients to fluticasone/salmeterol, and 165 patients to montelukast after a phase-in period during which mild asthma was stabilized on an inhaled corticosteroid. Dr. Peters said all patients took a pill and used inhalers without knowing which one of their treatments had an active ingredient and which two were placebo.

The population was evenly divided between men and women and had an average age of 31 years. About 18% of patients were children, and more than a third were African American or Hispanic. As a group, they were longtime asthma patients with an average of 16 years since diagnosis. Dr. Peters characterized the participants as “the group we are used to seeing.”

The trial's primary outcome was time to treatment failure, which the investigators defined in seven ways, including physician judgment. Patients who had treatment failures could have more than one reason for a treatment failure.

There were 50 treatment failures with montelukast, 34 with fluticasone, and 33 with fluticasone/salmeterol. The most common reason was a 20% or greater drop in forced expiratory volume in 1 second (FEV₁), which 48% of patients with treatment failures experienced: 26 patients on montelukast, 16 on the combination, and 14 on single-agent fluticasone.

Three components of asthma exacerbation accounted for a total of 48% of treatment failures: systemic steroids, inhaled corticosteroid use (not counting exercise medication), and urgent care. The proportion of patients with asthma exacerbation was similar: 13% with montelukast, 11% with fluticasone/salmeterol, and 10% with fluticasone alone. The only significant difference was in inhaler use when montelukast was compared with fluticasone/salmeterol (23% vs. 17%).

In other measures, Dr. Peters said montelukast was “slightly inferior” for nocturnal awakenings, prebronchodilator FEV₁, and responses on the Asthma Control Questionnaire. Fluticasone/salmeterol was “slightly superior” for morning peak expiratory flow. He reported no difference in the Asthma Symptom Utility Index, Adult Asthma Quality of Life, serious adverse events, or percentage of symptom-free days (79% vs. 86%). For all three groups, most days were symptom free and rescue inhaler use was infrequent. Adherence is an underlying issue, he said in an interview.

SAN DIEGO — Once-a-day step-down therapy can be an option for patients with mild, persistent asthma that has been stabilized by an inhaled corticosteroid, according to preliminary results from a 500-patient clinical trial presented at the international conference of the American Thoracic Society.

Dr. Stephen P. Peters said one puff a day of a fluticasone (100 mcg) and salmeterol (50 mcg) combination was as effective as 100 mcg of low-dose fluticasone twice a day. Only 20% of patients on either therapy failed treatment in the 15-week study.

A third group of patients did not fare as well on a pill containing 5 mg or 10 mg of montelukast each day. About 30% of patients failed treatment. Investigators calculated the relative risk of treatment failure as 60% higher than with fluticasone alone or fluticasone/salmeterol. Even so, the patients on montelukast fared well enough that all three regimens are viable, said Dr. Peters, director of research in pulmonary and critical care medicine at Wake Forest University, Winston-Salem, N.C.

“Although twice-a-day inhaled corticosteroid remains the treatment of choice for persistent asthma, alternatives could be considered on a case-by-case basis,” he said, citing the fluticasone/salmeterol combination. “There are still a lot of folks … who also did well, even on montelukast.”

The study, known as the Leukotriene Modifier or Corticosteroid or Corticosteroid-Salmeterol Trial, was sponsored by the American Lung Association's Asthma Clinical Research Centers. An unrestricted grant from GlaxoSmithKline provided financial support.

The trial randomized 168 patients to fluticasone, 162 patients to fluticasone/salmeterol, and 165 patients to montelukast after a phase-in period during which mild asthma was stabilized on an inhaled corticosteroid. Dr. Peters said all patients took a pill and used inhalers without knowing which one of their treatments had an active ingredient and which two were placebo.

The population was evenly divided between men and women and had an average age of 31 years. About 18% of patients were children, and more than a third were African American or Hispanic. As a group, they were longtime asthma patients with an average of 16 years since diagnosis. Dr. Peters characterized the participants as “the group we are used to seeing.”

The trial's primary outcome was time to treatment failure, which the investigators defined in seven ways, including physician judgment. Patients who had treatment failures could have more than one reason for a treatment failure.

There were 50 treatment failures with montelukast, 34 with fluticasone, and 33 with fluticasone/salmeterol. The most common reason was a 20% or greater drop in forced expiratory volume in 1 second (FEV₁), which 48% of patients with treatment failures experienced: 26 patients on montelukast, 16 on the combination, and 14 on single-agent fluticasone.

Three components of asthma exacerbation accounted for a total of 48% of treatment failures: systemic steroids, inhaled corticosteroid use (not counting exercise medication), and urgent care. The proportion of patients with asthma exacerbation was similar: 13% with montelukast, 11% with fluticasone/salmeterol, and 10% with fluticasone alone. The only significant difference was in inhaler use when montelukast was compared with fluticasone/salmeterol (23% vs. 17%).

In other measures, Dr. Peters said montelukast was “slightly inferior” for nocturnal awakenings, prebronchodilator FEV₁, and responses on the Asthma Control Questionnaire. Fluticasone/salmeterol was “slightly superior” for morning peak expiratory flow. He reported no difference in the Asthma Symptom Utility Index, Adult Asthma Quality of Life, serious adverse events, or percentage of symptom-free days (79% vs. 86%). For all three groups, most days were symptom free and rescue inhaler use was infrequent. Adherence is an underlying issue, he said in an interview.