Fluticasone propionate/salmeterol combination provides more effective asthma control than low-dose inhaled corticosteroid plus montelukast

doi:10.1067/mai.2000.110920

Journal of Allergy and Clinical Immunology

Volume 106, Issue 6, December 2000, Pages 1088-1095

https://doi.org/10.1067/mai.2000.110920 Get rights and content

Abstract

Background: Asthma is a disease of chronic inflammation and bronchoconstriction. Inhaled corticosteroids (ICSs) provide important anti-inflammatory treatment but may not provide optimal control of asthma when taken alone. Two therapeutic alternatives for enhanced asthma control are to substitute the combination of fluticasone propionate (FP) and salmeterol (FP/Salm Combo) through the Diskus inhaler or to add montelukast to existing ICS therapy. Objective: We compared the efficacy and safety of FP/Salm Combo through the Diskus inhaler versus montelukast added to FP (FP + montelukast) in patients whose symptoms were suboptimally controlled with ICS therapy. Methods: We performed a multicenter, double-blind, double-dummy, parallel-group, 12-week study in 447 patients with asthma who were symptomatic at baseline while receiving low-dose FP. Patients were treated for 12 weeks with one of the following: (1) combination of FP 100 μg plus salmeterol 50 μg twice daily through the Diskus inhaler, or (2) FP 100 μg twice daily through the Diskus inhaler plus oral montelukast 10 mg once daily. Results: FP/Salm Combo treatment provided better overall asthma control than FP + montelukast with significantly greater improvements in morning peak expiratory flow (+24.9 L/min vs +13.0 L/min, P < .001), evening peak expiratory flow (+18.9 L/min vs +9.6 L/min, P < .001), and forced expiratory volume in 1 second (+0.34 L vs +0.20 L, P < .001), as well as a change in the percentage of days with no albuterol use (+26.3% vs +19.1%, P = .032) and the shortness of breath symptom score (–0.56 vs –0.40, P = .017). The groups had comparable improvements in chest tightness, wheeze, and overall symptom scores. Asthma exacerbation rates were significantly lower (P = .031) in the FP/Salm Combo group (4 patients, 2%) than in the FP + montelukast group (13 patients, 6%). Adverse event profiles were comparable. Conclusion: Symptomatic patients on low-dose ICS therapy had significantly greater improvement in asthma control when switched to the FP/Salm Combo than when montelukast was added to ICS therapy. (J Allergy Clin Immunol 2000;106:1088-95.)

Section snippets

Patient selection

Male and female patients aged 15 years and older were eligible if they had had asthma for at least 6 months and if they had been taking low-to-moderate doses of an ICS for at least 30 days before screening. This included BDP 252 to 420 μg/d, budesonide 400 μg/d, flunisolide 1000 μg/d, FP 176 to 220 μg/d, or triamcinolone acetonide 600 to 800 μg/d. At the screening visit, all patients were required to have a forced expiratory volume in 1 second (FEV₁) between 50% and 80% of the predicted normal

Results

In total, 447 patients (87% of whom were white and 92% of whom had had asthma for ≥ 5 years) were randomly assigned to double-blind treatment: 222 in the FP/Salm Combo group and 225 in the FP + montelukast group. The treatment groups were comparable with respect to age, sex, and pulmonary function at screening and the end of run-in (Table I).

. Demographics and screening/baseline pulmonary function

Empty Cell	FP/Salm Combo	FP + Montelukast
No. of patients	222	225
Age (y)
Mean (SD)	40.2 (14.4)	43.0 (13.7)
Range	15-79

Discussion

This study demonstrated that patients whose symptoms were suboptimally controlled with ICS therapy alone had significantly greater improvement in asthma control and significantly fewer asthma exacerbations when their treatment was switched to FP/Salm Combo through the Diskus inhaler than when montelukast was added to low-dose FP therapy.

No significant differences were observed between treatment groups for wheeze, chest tightness, and overall symptoms. However, the patient-reported symptom

Acknowledgements

We thank Amy Schaberg for her assistance with preparation and editing of this manuscript.

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^☆: Supported by a grant from Glaxo Wellcome Inc, Research Triangle Park, NC.

^☆☆: Reprint requests: Harold S. Nelson, MD, National Jewish Medical and Research Center, 1400 Jackson St, Denver, CO 80206.

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Asthma, rhinitis, other respiratory diseasesFluticasone propionate/salmeterol combination provides more effective asthma control than low-dose inhaled corticosteroid plus montelukast☆,☆☆

Abstract

Section snippets

Patient selection

Results

Discussion

Acknowledgements

National Asthma Education and Prevention Program. Guidelines for the diagnosis and management of asthma. Expert panel report II

Diskus and Diskhaler: efficacy and safety of fluticasone propionate via two dry powder inhalers in subjects with mild-to-moderate persistent asthma

Ann Allergy Asthma Immunol

Inhaled fluticasone propionate delivered by means of two different multidose powder inhalers is effective and safe in a large pediatric population with persistent asthma

J Allergy Clin Immunol

A study on the clinical equivalence and patient preference of fluticasone propionate 250 microg twice daily via the Diskus/Accuhaler inhaler or the Diskhaler inhaler in adult asthmatic patients

J Asthma

Fluticasone propionate powder: oral corticosteroid-sparing effect and improved lung function and quality of life in patients with severe chronic asthma

J Allergy Clin Immunol

Added salmeterol versus higher-dose corticosteroid in asthma patients with symptoms on existing inhaled corticosteroid

Lancet

Comparison of the addition of salmeterol to inhaled steroids with doubling of the dose of inhaled steroids

Am J Respir Crit Care Med

Addition of salmeterol versus doubling the dose of fluticasone propionate in patients with mild to moderate asthma

Thorax

The addition of salmeterol to fluticasone propionate versus increasing the dose of fluticasone propionate in patients with persistent asthma

Ann Allergy Asthma Immunol

Salmeterol added to inhaled corticosteroid therapy is superior to doubling the dose of inhaled corticosteroids: a randomized clinical trial

J Asthma

Concurrent use of salmeterol with inhaled corticosteroids is more effective than inhaled corticosteroid dose increases

Allergy Asthma Proc

Salmeterol and fluticasone propionate (50/250 microg) administered via combination Diskus inhaler: as effective as when given via separate Diskus inhalers

Can Respir J

Salmeterol/fluticasone propionate (50/500microg) in combination in a Diskus inhaler (Seretide) is effective and safe in the treatment of steroid-dependent asthma

Respir Med

Combined salmeterol 50mg and fluticasone propionate 250mg in the Diskus device for the treatment of asthma

Am J Respir Crit Care Med

Salmeterol and fluticasone propionate combined in a new powder inhalation device for the treatment of asthma: a randomized, double-blind, placebo-controlled trial

J Allergy Clin Immunol

Effects of leukotrienes in the treatment of asthma

Am J Respir Crit Care Med

Alternative agents for anti-inflammatory treatment of asthma

J Allergy Clin Immunol

The role of leukotrienes in inflammation

Ann Intern Med

Leukotriene pathway inhibitors in asthma and chronic obstructive pulmonary disease

Clin Exp Allergy

Randomized, placebo controlled trial of effect of a leukotriene receptor antagonist, montelukast, on tapering inhaled corticosteroids in asthmatic patients

BMJ

Asthma, rhinitis, other respiratory diseases
Fluticasone propionate/salmeterol combination provides more effective asthma control than low-dose inhaled corticosteroid plus montelukast☆,☆☆