Dose-response relationship of inhaled budesonide in adult asthma: a meta-analysis

Abstract

The aim of this study was to examine the dose-response relationship of inhaled budesonide in adolescents and adults with asthma.A meta-analysis was carried out on placebo-controlled, randomised clinical trials, presenting data on at least one outcome measure of asthma and using at least two doses of budesonide, delivered by turbuhaler or metered-dose inhalerzspacer twice daily.A total of six studies of 1,435 adolescents and adults, with mild to moderately severe asthma, met the inclusion criteria for the meta-analysis. A negative exponential model indicated that 80% of the benefit at 1,600 mg?day -1 was achieved at doses of y200-400 mg?day -1 and 90% by 300-600 mg?day -1 . Meta-regression with a quadratic term in dose showed that the maximum effect was obtained with doses of y1,000 mg?day -1 . In conclusion, the available published data indicate that, in adolescents and adults with mild to moderate asthma, most of the therapeutic benefit of budesonide delivered by turbuhaler or metered-dose inhalerzspacer is achieved with a dose of y400 mg?day -1 and the maximum effect is achieved at y1,000 mg?day -1 . This conclusion is qualified by the recognition that there is considerable individual variability in the response to inhaled corticosteroids and that the subjects included in this meta-analysis had predominantly mild to moderate asthma. In a recent meta-analysis of the dose-response relationship of fluticasone, it was shown that most of the therapeutic benefit is achieved with doses of 100-250 mg?day -1 , and that the maximum effect is obtained at y500 mg?day -1 in adolescents and adults with asthma [1]. This therapeutic dose range is two-fold lower than that recommended in the international and national consensus guidelines and formularies, and the dose commonly prescribed in clinical practice [2][3][4]. In view of this disparity and in response to the recommendations of the Cochrane Centre [5], the current authors have further investigated the therapeutic dose range of inhaled corticosteroids by undertaking a similar meta-analysis of the doseresponse relationship of budesonide. MethodsA search of Medline was conducted from Jan 1966 to Jan 2003 and of Embase from Jan 1980 to Jan 2003. On Medline, studies were searched using a combination of the keywords "budesonide" and "dose" or "dosage". AstraZeneca, the manufacturer of budesonide, was also asked for details of all relevant studies; no additional studies were identified. No relevant studies published in other languages were found on Medline or Embase. Finally, the reference lists of relevant studies were examined and no other studies were found. Inclusion criteriaTwo people examined each paper9s title and abstract, and then the full paper if necessary. To be included in the primary meta-analysis, studies had to meet all of the following criteria: a double-blind, placebo-controlled, randomised trial involving two or more doses of budesonide, delivered by turbuhaler or metered-dose inhaler (MDI)zspacer device twice daily, in adolescents (agedw12 yrs) or...

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