Combined corticosteroid and long-acting beta-agonist in one inhaler versus long-acting beta-agonists for chronic obstructive pulmonary disease

 

Abstract

Background

The co-administration of inhaled corticosteroids and long-acting beta-agonists in a combined inhaler is intended to facilitate adherence to medication regimens, and to improve efficacy in COPD. In this review they are compared with mono component long-acting beta-agonists.

Objectives

To assess the efficacy of combined inhaled corticosteroids and long-acting beta-agonists preparations with mono component long-acting beta-agonists in adults with chronic obstructive pulmonary disease.

Search methods

We searched the Cochrane Airways Group Specialised Register of trials. The date of the most recent search is April 2007.

Selection criteria

Studies were included if they were randomised and double-blind. Studies could compare a combined inhaled corticosteroids and long-acting beta-agonist preparation with component long-acting beta-agonist preparation.

Data collection and analysis

Two authors independently assessed study risk of bias and extracted data. The primary outcomes were exacerbations, mortality and pneumonia. Health-related quality of life (measured by validated scales), lung function and side-effects were secondary outcomes. Dichotomous data were analysed as fixed effect odds ratios or rate ratios with 95% confidence intervals, and continuous data as mean differences and 95% confidence intervals.

Main results

Ten studies of good methodological quality met the inclusion criteria, randomising 7598 participants with severe chronic obstructive pulmonary disease. Eight studies assessed fluticasone/salmeterol, and two studies budesonide/formoterol. The exacerbation rates with combined inhalers were reduced in comparison to long-acting beta-agonists alone (Rate Ratio 0.82, 95% CI 0.78 to 0.88). There was no significant difference in mortality between combined inhalers and long-acting beta-agonists alone. Pneumonia occurred more commonly with combined inhalers (OR 1.58; (95% CI 1.32 to 1.88). There was no significant difference in terms of hospitalisations, although the two studies contributing data to this outcome may have been drawn from differing populations. Combination was more effective than long-acting beta-agonists in improving quality of life measured by the St George Respiratory Questionnaire, and the Chronic Respiratory Questionnaire, and predose and post dose FEV1.

Authors' conclusions

Combination therapy was more effective than long-acting beta-agonists in reducing exacerbation rates, although the evidence for the effects on hospitalisations was mixed, and requires further exploration. No significant impact on mortality was found even with additional information from the TORCH trial. The superiority of combination inhalers should be viewed against the increased risk of side-effects, particularly pneumonia. Additional studies on budesonide/formoterol are required and more information would be useful of the relative benefits and adverse event rates with different doses of inhaled corticosteroids.

 

Plain language summary

Combination therapy of inhaled steroids and long-acting beta-agonists versus long-acting beta-agonists alone for chronic obstructive pulmonary disease

Combinations of two classes of medication in one inhaler have been developed to treat people with COPD as this may make it easier to take the medication than using separate inhalers. Two types of combined inhaler exist currently: budesonide/formoterol (BDF - 'Symbicort'), and fluticasone/salmeterol (FPS - 'Advair', 'Viani' or 'Seretide'). The results of the studies showed that combined inhalers were effective and reduced the frequency of exacerbations compared with their long-acting beta-agonist component, but there was an overall increased risk of pneumonia with combined inhalers. Future research is required to show whether the drugs reduce hospitalisations, and to better estimate the increased risk of pneumonia. More trials with budesonide/formoterol are required, and comparing different doses of inhaled corticosteroids.

 

摘要

背景

以混合糖皮質類固醇(ICS)與Longacting betaagonist(LABA)的單一吸入劑或單獨使用LABA針對Chronic obstructive pulmonary disease(COPD)進行治療

將LABA與ICS混合搭配形成一混合式吸入劑能增加病患對醫囑的服從性，促進COPD的療效。在本文獻回顧中將比較混合式吸入劑和單獨使用LABA的效用。

目標

本研究主要係在患有COPD的成人患者身上，比較使用混合型ICS和LABA吸入劑與單獨使用LABA的治療效果。

搜尋策略

我們搜尋了Cochrane Airways Group Specialised Register資料庫中的試驗資料，搜尋至2007年4月。

選擇標準

研究中納入了隨機性雙盲試驗的結果，並將ICS和LABA的混合式藥物與單一成分LABA的治療效果進行比較。

資料收集與分析

有兩個相互獨立的審閱者分別對試驗品質及萃取資料進行檢視；主要結果係界定為症狀惡化、死亡或感染肺炎，與健康有關的生活品質(利用已經通過驗證的評分方法進行評估)、肺功能和副作用則列為次要結果。二元資料經過分析後以固定效果勝算比(fixed effect odds ratios，OR)表示，連續性資料則以平均差異和95％信賴區間之數據表示；靈敏度分析是將數據整合以隨機影響模式的方式呈現。

主要結論

研究中納入了10個具有良好方法學品質的試驗結果，其中隨機選取了7598名患有嚴重COPD的患者；在這10個試驗結果中，有8個是針對fluticasone/salmeterol(FPS)進行研究，另外2個則是針對budesonide/formoterol(BDF)進行研究。相對於單一LABA，使用混合式吸入劑可以降低症狀惡化的比例(比例值為0.82，95％的信賴區間介於0.78至0.88之間)；兩者在致死率上沒有明顯區別，但是使用混合式吸入劑卻較常出現肺炎案例(OR值為0.62，95％的信賴區間介於1.35至1.94之間)。雖然數據採樣自不同群落的受試對象，但結果顯示兩種治療方法在住院率上並沒有顯著的差異。此外，研究也指出，混合式吸入劑比LABA對於改善生活品質更有效果，其中生活品質的評量方法係根據St George Respiratory Questionnaire和Chronic Respiratory Questionnaire等評量表及測量治療前後FEV1數值以進行評分所得。

作者結論

對於降低症狀惡化比例來說，混合式吸入劑比單獨使用LABA更具效果；但是不同藥物治療對於住院率影響的相關資料是透過彙整所得到的，所以應更進一步精確探討。即使取得額外的TORCH試驗資料，也並未發現在致死率上有顯著的影響。雖然混合式吸入劑效果較好，但副作用的風險也較高，尤其是肺炎。也須針對BDF與不同劑量的ICS進行研究，以瞭解更多有關不良反應發生率和對患者相對好處的資訊。

翻譯人

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

總結

將兩種不同類別的藥物混合形成一種吸入劑的方法，因為操作方便、不需分別用藥，所以發展來治療COPD的患者。目前有兩種常用的混合式吸入劑，分別是budesonide/formoterol(簡稱BDF，商品名為Symbicort)和fluticasone/salmeterol(簡稱FPS，商品名為Advair、Viani或Seretide)。研究結果顯示，與單獨使用LABA相較，BDF和FPS都具療效，且可以降低症狀惡化的頻率；但使用混合式吸入劑卻會增加肺炎發作的風險。應由進一步的研究來說明治療藥物是否降低住院率，並且針對肺炎發作的風險進行較精確的評估。此外，也需針對BDF進行更多試驗，並與不同劑量ICS的療效作比較。