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Formoterol was more effective than terbutaline when taken as needed for moderate to severe asthma
  1. Paul M O'Byrne, MB
  1. McMaster University and St. Joseph's Hospital Hamilton, Ontario, Canada

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 QUESTION: In patients with moderate to severe asthma who use an inhaled corticosteroid but still require as needed medication, is formoterol (a long acting β2 agonist) more effective than terbutaline (a short acting β2 agonist) when used as needed?

    Design

    12 week randomised (allocation concealed*), blinded (patients and investigators initially),* controlled trial.

    Setting

    35 centres in Greece, the Netherlands, Norway, and Sweden.

    Patients

    362 patients who were ≥18 years of age (mean age 47 y, 57% women); had had asthma for ≥6 months; had been treated with a constant dose of an inhaled corticosteroid for ≥4 weeks; had an FEV1 of ≥50% of the predicted value, which increased by ≥12% after inhalation of 1.5 mg of terbutaline; and used their relief inhaler about 3–8 times per day on ≥7 days of the 2 week run in period. Exclusion criteria were need for ≥12 inhalations of rescue medication during the run in period or serum potassium level outside of reference range. Follow up was 85%.

    Intervention

    Patients were allocated to inhaled formoterol, 4.5 μg (metered dose 6 μg) (n=182), or inhaled terbutaline, 0.5 mg (n=180), for 12 weeks. Patients were told to take the medication only when needed.

    Main outcome measures

    Time to first severe exacerbation. Secondary outcomes were morning and evening peak flow rate, FEV1, symptoms, number of inhalations of relief medication, and safety.

    Main results

    Analysis was by intention to treat. Fewer patients in the formoterol group than in the terbutaline group had ≥1 exacerbation {p=0.02} (table). The time to first exacerbation was longer in the formoterol group than in the terbutaline group (p=0.013). Morning and evening peak expiratory flow rates increased in the formoterol group and decreased in the terbutaline group (mean difference 11 l/min, 95% CI 3 to 20 l/min for morning; 8 l/min, CI 0 to 15 l/min for evening). The reduction in number of inhalations of relief medication was higher in the formoterol group than in the terbutaline group (mean difference 0.76 inhalations/d, CI 0.33 to 1.18). Prebronchodilator FEV1 was increased in the formoterol group relative to the terbutaline group (mean ratio 105%, CI 101% to 108%). Both treatments were well tolerated. Groups did not differ for change in symptom scores.

    Formoterol v terbutaline for moderate to severe asthma

    Conclusion

    In patients with moderate to severe asthma, formoterol was more effective than terbutaline when taken as needed.

    Commentary

    Formoterol is a long acting, inhaled, β2 adrenergic receptor agonist with interesting pharmacological properties. Despite having a duration of bronchodilating activity of >12 hours in patients with asthma, its onset of action is similar to the shorter acting inhaled β2 adrenergic receptor agonists, such as terbutaline or salbutamol. In addition, the duration of the systemic pharmacological activity of formoterol (resulting in potential side effects) is similar to the shorter acting inhaled β2 agonists. This characteristic allows formoterol to be used for “as needed” treatment of symptoms.

    The study by Tattersfield et al compared formoterol and terbutaline used “as needed” in a well designed study in adult patients who had moderately severe and uncontrolled asthma. The main outcome variable, time to first severe asthma exacerbation, is an important outcome in asthma but is not often used in clinical trials.

    This study showed that fewer inhalations of “as needed” formoterol were needed and that, somewhat surprisingly, the time to the first severe exacerbation was longer in the formoterol group. This effect on exacerbations has been previously described in a similar patient population, when formoterol, taken regularly twice daily, was added to low or moderate doses of the inhaled corticosteroid budesonide.1 The current study suggests that the ability of formoterol to reduce the risk for a severe asthma exacerbation is so robust that it can be shown even when the drug is used less frequently. These results are important to clinicians treating asthma because severe asthma exacerbations are the most dangerous events that can occur in patients with asthma, as well as being the most demanding and expensive for the healthcare system. This benefit of formoterol was not accompanied by an increase in β2 agonist related side effects. The study has convincingly shown that in addition to the already well accepted benefits of the regular use of inhaled formoterol, “as needed” use provides more clinical benefit to people with asthma than does use of the shorter acting terbutaline.

    References

    View Abstract

    Footnotes

    • Source of funding: AstraZeneca R&D.

    • For correspondence: Professor A E Tattersfield, Division of Respiratory Medicine, City Hospital, Nottingham NG5 1PB, UK. Fax +44 (0)115 840 4771.

    • * See glossary.

    • p Value calculated from data in article.

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