Combination fluticasone and salmeterol versus fixed dose combination budesonide and formoterol for chronic asthma in adults and children

 

Abstract

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 FEV₁ 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 outcomes

The 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 outcomes

Lung 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.

 

Plain language summary

Different combinations of inhaled steroids and long-acting beta-agonists for chronic asthma (fluticasone/salmeterol versus budesonide/formoterol)

People with persistent asthma often require an additional treatment to regular inhaled steroids. Some preparations of long-acting beta-agonists are delivered in the same inhaler device as the inhaled corticosteroids. Inhaled steroids help to treat inflammation of the airway and long-acting beta-agonists help the airway to relax, improving symptoms and lung function. This systematic review examined randomised controlled trials comparing two commonly available combinations administered at a fixed dose through a single inhaler, fluticasone/salmeterol and budesonide/formoterol. We included five studies which recruited 5537 people. The trials were generally well designed but only recruited adults and adolescents and not children. Participants were already taking regular inhaled steroids before the studies commenced and had mild or moderate asthma based on tests of their airway. We found that the number of people who required treatment with oral steroids and admission to hospital was similar between the treatments, but due to the statistical uncertainty of this result we could not rule out important differences in favour of either drug combination. Additional trials would enable us to draw more reliable conclusions about how well these drugs work compared with each other. We also looked at serious adverse events. Again, the results did not indicate that one combination was clearly better than the other, but again these results were imprecise so we cannot be certain. However, lung function and rescue medication use were similar between the treatments. We could not assess the relative effects of these drugs on mortality because there were so few deaths which leads to statistical uncertainty; out of the five studies, one person died. Quality of life was measured in different ways in two studies and we could not determine how the treatments compared in this respect. Further studies are needed to strengthen and better explain these findings. In particular studies which assess the effects of these therapies in children and studies which measure quality of life are a priority.

 

摘要

背景

合併fluticasone及salmeterol相較於合併固定劑量budesonide及formoterol治療成人及兒童氣喘

合併治療常被建議用於吸入式類固醇無法充分控制病情的氣喘病人之維持治療。Fluticasone/salmeterol(FP/SAL)及budesonide/formoterol(BUD/F)曾被與其中單一成份作評估比較，但需要對此兩組治療作面對面的比較。

目標

評估Fluticasone/salmeterol及budesonide/formoterol在氣喘控制、安全性及肺功能的相對效果。

搜尋策略

我們以預設詞彙搜尋Cochrane Airways Group register of trials。我們執行額外的人工搜尋藥品製造商的網站及線上試驗登錄。搜尋至2008年5月。

選擇標準

比較固定劑量FP/SAL及BUD/F治療至少12週的隨機研究符合選擇。交叉研究則被排除。我們的主要判斷指標為：i) 惡化需突然使用口服類固醇，ii) 住院治療及iii) 嚴重不良事件

資料收集與分析

兩位審查者獨立地評估研究是否合適納入回顧。我們合併連續數據結果為平均差(MD)及二分類數據結果為勝算比(OR)。

主要結論

有五項研究符合回顧納入標準(5537名參與者)。主要判斷指標：惡化需口服類固醇並無顯著差異(OR 0.89；95% CI 0.73至1.09，三項研究，4515名參與者)。惡化導致住院治療亦無顯著差異(OR 1.29；95% CI 0.68至2.47，四項研究，4879名參與者)。嚴重不良事件在兩種治療間並無顯著差異(OR 1.47；95% CI 0.75至2.86，三項研究，4054名參與者)。次要判斷指標：肺功能結果、症狀、救援藥物、惡化而致到急診看病或住院，以及不良事件等在兩種治療間並無顯著差異。

作者結論

本回顧的證據顯示FP/SAL及BUD/F在口服類固醇和住院的需求兩者間未達統計學意義。然而，信賴區間值並未排除兩種治療間在減少惡化或引致不良事件方面在臨床上有重要的差異。主要判斷指標之信賴區間寬度顯示應有進一步試驗對此等藥物合併的相對效果作更佳的確認。雖然本回顧是要評估此等藥物在成人及兒童的效果，但沒有找到用於12歲以下的試驗，因而此一領域的研究須優先考慮。

翻譯人

本摘要由中國醫藥大學附設醫院陳祖裕翻譯。

此翻譯計畫由臺灣國家衛生研究院(National Health Research Institutes, Taiwan)統籌。

總結

持續的氣喘常需要合併吸入式類固醇(ICS)及長效β2促效劑(LABA)。本系統性研究檢視比較fluticasone/salmeterol(FP/SAL)及budesonide/formoterol(BUD/F)這兩種採單一吸入器及固定劑量的常用組合之隨機對照試驗。我們發現需口服類固醇和住院的病人數目在兩種治療間乃相近的，但進一步的試驗可改善我們所估計的準確性。在肺功能、使用救援藥物以及不良事件未發現有統計學上的差異。需要以不同類型病人來針對這些問題進行設計良好的研究來確認及對這些發現有更佳的解釋。評估這些治療在兒童的效果之研究尤其需要優先考慮。