Combination fluticasone and salmeterol versus fixed dose combination budesonide
and formoterol for chronic asthma in adults and children.
Author(s): Lasserson TJ, Ferrara G, Casali L.
Affiliation(s): Cochrane Editorial Unit, The Cochrane Collaboration, 13 Cavendish Square, London,
UK, W1G 0AN.
Publication date & source: 2011, Cochrane Database Syst Rev. , (12):CD004106
BACKGROUND: Long-acting beta-agonists are a common second line treatment in
people with asthma inadequately controlled with inhaled corticosteroids. Single
device inhalers combine a long-acting beta-agonist with an inhaled steroid
delivering both drugs as a maintenance treatment regimen. This updated review
compares two fixed-dose options, fluticasone/salmeterol FP/SALand
budesonide/formoterol, since this comparison represents a common therapeutic
choice.
OBJECTIVES: To assess the relative effects of fluticasone/salmeterol and
budesonide/formoterol in people with asthma.
SEARCH METHODS: We searched the Cochrane Airways Group register of trials with
prespecified terms. We performed additional hand searching of manufacturers' web
sites and online trial registries. Search results are current to June 2011.
SELECTION CRITERIA: We included randomised studies comparing fixed dose
fluticasone/salmeterol and budesonide/formoterol in adults or children with a
diagnosis of asthma. Treatment in the studies had to last for a minimum of 12
weeks.
DATA COLLECTION AND ANALYSIS: Two authors independently assessed studies for
inclusion in the review. We combined continuous data outcomes with a mean
difference (MD), and dichotomous data outcomes with an odds ratio (OR). We
assessed the quality of the evidence using the Grading of Recommendations
Assessment, Development and Evaluation (GRADE) system.
MAIN RESULTS: Five studies met the review entry criteria (5537 adults). Study
populations entered the studies having previously been treated with inhaled
steroids and had moderate or mild airway obstruction (mean FEV(1) predicted
between 65% and 84% at baseline). Most of the studies assessed treatment over a
period of six months. The studies were at a low risk of selection and
performance/detection bias, although we could not determine whether missing data
had an impact on the results. Availablility of outcome data was
satisfactory.Primary outcomesThe odds ratio for exacerbations requiring oral
steroids was lower with fluticasone/salmeterol but did not reach statistical
significance (OR 0.89, 95% confidence interval (CI) 0.74 to 1.07, four studies, N
= 4949). With an assumed risk with budesonide/formoterol of 106/1000 participants
requiring oral steroids, treatment with fluticasone/salmeterol would lead to
between 25 fewer and seven more people per 1000 experiencing a course of oral
steroids. Although the odds of hospital admission was higher with
fluticasone/salmeterol, this did not reach statistical significance (OR 1.29, 95%
CI 0.68 to 2.47, four studies, 4879 participants). With an assumed risk in the
budesonide/formoterol of 7/1000, between two fewer and 10 more people per 1000
would be hospitalised on fluticasone/salmeterol. The odds of a serious adverse
event related to asthma was higher with fluticasone/salmeterol but did not differ
significantly between treatments (OR 1.47, 95% CI 0.75 to 2.86, three studies,
4054 participants). With an assumed risk in the budesonide/formoterol of 7/1000,
between two fewer and 13 more people per 1000 would experience a serious adverse
event on fluticasone/salmeterol.Secondary outcomesLung function outcomes,
symptoms, rescue medication, composite of exacerbations leading to either
emergency department visit or hospital admission, withdrawals and adverse events
did not differ statistically between treatments. Assessment of quality of life
was limited to two studies, both of which gave results that did not reach
statistical significance. One study reported one death out of 1000 participants
on fluticasone/salmeterol and no deaths in a similar number of participants
treated with budesonide/formoterol. No deaths were reported in the other studies.
AUTHORS' CONCLUSIONS: Statistical imprecision in the effect estimates for
exacerbations and serious adverse events do not enable us to conclude that either
therapy is superior. The uncertainty around the effect estimates justify further
trials to provide more definitive conclusions; the overall quality of evidence
based on GRADE recommendations for the three primary outcomes and withdrawals due
to serious adverse events was moderate. We rated the quality of evidence for
mortality to be low. Results for lung function outcomes showed that the drugs
were sufficiently similar that further research is unlikely to change the
effects. No trials were identified in the under-12s and research in this
population is a high priority. Evaluation of quality of life is a priority for
future research.
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