Chest
Volume 115, Issue 2, February 1999, Pages 336-342
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Clinical Investigations
ASTHMA
Therapeutic Effect of Zafirlukast as Monotherapy in Steroid-Naive Patients With Severe Persistent Asthma

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Study objectives

We evaluated the efficacy of the leukotriene receptor antagonist zafirlukast (Accolate®), 20 mg twice daily, as monotherapy in patients with severe persistent asthma (defined by an FEV1 < 60% of predicted before treatment and frequent night-time symptoms).

Design

Data were analyzed from a subgroup of 261 steroid-naive patients (zafirlukast, n = 149; placebo, n = 112) from four randomized, double-blind, placebo-controlled, 13-week trials with similar experimental designs, entry criteria, and clinical assessments.

Patients

These patients were mostly men (57%) older than 30 years (56%) with pulmonary obstruction, ie, FEV1/FVC ratio < 0.7 (79%), and reversible airway disease demonstrated by a 15% increase in FEV1 after inhaled bronchodilator use.

Results

At end point, patients who received zafirlukast monotherapy had significant (p < 0.05) improvements from baseline, and compared with placebo, in FEV1, morning and evening peak expiratory flow (PEF), daytime asthma symptoms, nighttime awakenings, and β2-agonist use. A stratified analysis based on the FEV1/FVC ratio showed an interaction between treatment and the amount of airflow obstruction for nighttime awakenings and mornings with asthma. Moreover, 37% of patients in both treatment groups had PEF variability ≥ 20% (an indirect measure of airway inflammation). Zafirlukast patients with PEF variability≥ 20% had increases from baseline in the morning and evening PEF of approximately 40 and 11 L/min, respectively. For patients who take zafirlukast and who have a PEF variability of < 20%, the morning and evening PEF increased by 25 and 30 L/min, respectively. Regardless of the degree of PEF variability, zafirlukast significantly (p < 0.05) increased morning and evening PEF compared with placebo.

Conclusion

Patients with severe persistent asthma who received zafirlukast as monotherapy had clinically significant improvements across all efficacy measures compared with placebo and significant reductions in PEF variability.

Section snippets

Trial Design

This analysis evaluated a subset of 261 men and women who received treatment with a 20-mg twice daily (bid) dose of zafirlukast (n = 149) or placebo (n = 112) in four randomized, double-blind, placebo-controlled, 13-week trials with similar study designs, entry criteria, and clinical assessments. All of the trials had three periods, including a 1-week screening, a 2- to 3-week, single-blind, placebo run-in, and 13 weeks of double-blind treatment. All four trials were conducted under the

Results

Two hundred sixty-one patients with severe persistent asthma (zafirlukast, n = 149; placebo, n = 112) were included in the subgroup analyses. More than half of this patient population consisted of men who were > 30 years of age and who had moderate pulmonary obstruction as demonstrated by an FEV1/FVC ratio of < 0.70 (Table 2). Baseline asthma characteristics were similar between the zafirlukast and placebo groups. On average, patients had a percent predicted FEV1 of approximately 53%, between

Discussion

This retrospective analysis in steroid-naive patients with severe persistent asthma was prompted by the finding that 261 patients from the zafirlukast clinical trial program who were diagnosed as having mild-to-moderate asthma on the basis of their treatment history met the NAEPP classification for severe persistent asthma. Although the ideal approach to therapy for these patients involves treatment with an optimized dose of inhaled corticosteroid therapy or combination therapy with inhaled

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For related editorial see page 313.

Dr. Kemp is a consultant to Zeneca Pharmaceuticals anda participating investigator in zafirlukast clinical trials. Financial support for this study was provided by Zeneca Pharmaceuticals, Wilmington, DE.

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