Combination formoterol and budesonide as maintenance and reliever therapy versus inhaled steroid maintenance for chronic asthma in adults and children

 

Abstract

Background

Traditionally inhaled treatment for asthma has been considered as preventer and reliever therapy. The combination of formoterol and budesonide in a single inhaler introduces the possibility of using a single inhaler for both prevention and relief of symptoms (single inhaler therapy).

Objectives

The aim of this review is to compare formoterol and corticosteroid in single inhaler for maintenance and relief of symptoms with inhaled corticosteroids for maintenance and a separate reliever inhaler.

Search methods

We last searched the Cochrane Airways Group trials register in September 2008.

Selection criteria

Randomised controlled trials in adults and children with chronic asthma.

Data collection and analysis

Two review authors independently assessed studies for inclusion and extracted the characteristics and results of each study. Authors or manufacturers were asked to supply unpublished data in relation to primary outcomes.

Main results

Five studies on 5,378 adults compared single inhaler therapy with current best practice, and did not show a significant reduction in participants with exacerbations causing hospitalisation (Peto OR 0.59; 95% CI 0.24 to 1.45) or treated with oral steroids (OR 0.83; 95% CI 0.66 to 1.03). Three of these studies on 4281 adults did not show a significant reduction in time to first severe exacerbation needing medical intervention (HR 0.96; 95% CI 0.85 to 1.07). These trials demonstrated a reduction in the mean total daily dose of inhaled corticosteroids with single inhaler therapy (mean reduction ranged from 107 to 267 micrograms/day, but the trial results were not combined due to heterogeneity). The full results from four further studies on 4,600 adults comparing single inhaler therapy with current best practice are awaited.

Three studies including 4,209 adults compared single inhaler therapy with higher dose budesonide maintenance and terbutaline for symptom relief. No significant reduction was found with single inhaler therapy in the risk of patients suffering an asthma exacerbation leading to hospitalisation (Peto OR 0.56; 95% CI 0.28 to 1.09), but fewer patients on single inhaler therapy needed a course of oral corticosteroids (OR 0.54; 95% CI 0.45 to 0.64). These results translate into an eleven month number needed to treat of 14 (95% CI 12 to 18), to prevent one patient being treated with oral corticosteroids for an exacerbation. The run-in for these studies involved withdrawal of long-acting beta₂-agonists, and patients were recruited who were symptomatic during run-in.

One study included children (N = 224), in which single inhaler therapy was compared to higher dose budesonide. There was a significant reduction in participants who needed an increase in their inhaled steroids with single inhaler therapy, but there were only two hospitalisations for asthma and no separate data on courses of oral corticosteroids. Less inhaled and oral corticosteroids were used in the single inhaler therapy group and the annual height gain was also 1 cm greater in the single inhaler therapy group, [95% CI 0.3 to 1.7 cm].

There was no significant difference found in fatal or non-fatal serious adverse events for any of the comparisons.

Authors' conclusions

Single inhaler therapy can reduce the risk of asthma exacerbations needing oral corticosteroids in comparison with fixed dose maintenance inhaled corticosteroids. Guidelines and common best practice suggest the addition of regular long-acting beta₂-agonist to inhaled corticosteroids for uncontrolled asthma, and single inhaler therapy has not been demonstrated to significantly reduce exacerbations in comparison with current best practice, although results of five large trials are awaiting full publication. Single inhaler therapy is not currently licensed for children under 18 years of age in the United Kingdom.

 

Plain language summary

Combination of formoterol and budesonide as single inhaler therapy versus inhaled corticosteroid maintenance and a separate reliever inhaler, or current best practice

A single combination inhaler containing formoterol and budesonide has been advocated for regular maintenance of asthma, with the option to increase the dose if the asthma flares up. This is sometimes known as single inhaler therapy. Single inhaler therapy can reduce the risk of asthma exacerbations needing oral corticosteroids in comparison with fixed dose maintenance inhaled corticosteroids. The trials were in people with asthma who had their maintenance treatment reduced and became symptomatic. These results have not yet been replicated in trials comparing single inhaler therapy with current best practice, and the results of five large trials are awaiting publication. The place of this new approach to asthma management must remain somewhat uncertain until all the trials are fully reported.

 

摘要

背景

對於患有慢性氣喘的幼童及成人，給予formoterol和budesonide的混合性藥物作為維持治療及舒緩治療vs給予吸入型類固醇維持治療使用的效果比較

一般的氣喘吸入性療法被認為具有保護和舒緩的效果。將formoterol和budesonide進行混合以形成單一藥劑，可能具有可以達到使用一種吸入劑卻同時具有症狀維持或舒緩(單一吸入劑治療法)的功效。

目標

比較將formoterol和budesonide調配為單一吸入劑以進行維持和舒緩治療，與使用ICS進行維持治療並搭配另一吸入劑進行舒緩治療的效果。

搜尋策略

針對Cochrane Airways Group trials register資料庫進行檢索，檢索至2008年9月。

選擇標準

納入針對慢性氣喘的幼童及成人患者進行的隨機對照試驗。

資料收集與分析

有2位獨立審閱作者分別評估可以被納入研究的試驗，並且將每一個研究的特點及結果摘錄出來。我們也會聯繫試驗作者與製造商以取得有關初級試驗的未公開數據。

主要結論

包含有5378位成人受試者的5個試驗被納入研究中，這些試驗係將單一吸入劑治療法與現行的最佳臨床實務進行比較，在患者因為症狀惡化而住院的比例(Peto OR值為0.59，95％的CI 介於0.24至1.45之間)或是需要使用口服式類固醇進行治療的比例(OR值為0.83，95％的CI 介於0.66至1.03之間)上並沒有明顯的下降趨勢，有3個試驗係以4281位成人為受試者，試驗結果並沒有顯示在第一次症狀嚴重惡化至需要藥物進行介入性治療的時間有明顯的縮短(HR值為0.96，95％的CI 介於0.85至1.07之間)，這些試驗證明了在進行單一吸入劑治療時可以使得每天ICS的平均使用總劑量下降(平均減少範圍介於每天107至267微克，但是這些試驗的結果因為異質性而沒有被合併)。其他針對4600位成人為受試者的4個試驗整體治療結果係將使用單一吸入劑治療與現行最佳治療效果進行比較。3個包含有4209位成人患者的試驗則是比較單一吸入劑治療與使用較高劑量budesonide進行維持療法並搭配使用terbutaline進行症狀舒緩這兩種療法的效果，使用單一治療劑治療對於患者因為氣喘症狀惡化而住院的比例上並沒有明顯降低的趨勢(Peto OR值為.56，95％的CI 介於0.28至1.09之間)，但是有少數接受單一吸入劑治療的患者需要使用一些口服式皮質類固醇(OR值為0.54，95％的CI 介於0.45至0.64之間)，換言之這個結果說明需要有14名患者進行11個月的治療(95％的CI 介於12至18之間)以預防一個患者發生惡化的症狀而需要使用口服式類固醇治療，要進入這些試驗必須要先停用LABA，且在進入試驗時患者必須具有相關症狀，有一個納入224名幼童的試驗，比較使用單一吸入劑治療和使用高劑量budesonide治療的效果，進行單一吸入劑治療的組別需要增加吸入式類固醇用量的患者比例有明顯降低的趨勢，但是仍有2名患者因為氣喘而住院，且缺乏使用口服皮質類固醇的分離數據，進行單一吸入劑治療的患者會使用較少的吸入劑及口服式皮質類固醇，且一般身高也會多1公分(95％的CI 介於0.3至1.7公分)，不論是哪種治療方法，在致命性和非致命性嚴重不良反應的發生機率均沒有顯著差異。

作者結論

與使用固定維持劑量ICS的組別相較，使用單一吸入劑治療的組別降低了氣喘惡化而需要使用口服式皮質類固醇的風險，氣喘治療指導方針和一般最佳治療實務結果推測規律性添加LABA至ICS中可以使用於無法控制的氣喘，且與最佳治療實務經驗相比，單一吸入劑治療並未被證實可以明顯降低症狀惡化的發生率，雖然目前有5個大型試驗的數據正等待被發表，在英國，單一吸入劑治療並不是目前被認為可以用來治療18歲以下幼童的氣喘治療法。

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

有人宣稱可以規律使用含有formoterol和budesonide的單一吸入劑來控制氣喘症狀，當氣喘突然發作時也可以增加使用劑量，有時候這樣的方法會被視為一種單一吸入劑治療，與使用固定劑量ICS進行氣喘維持治療相比，單一吸入至治療可以降低氣喘惡化而需要使用口服式皮質類固醇的風險。本研究的試驗係將氣喘患者用來維持症狀的ICS劑量降低使其症狀發作來加以進行，在比較單一吸入劑治療與現行最佳治療結果時。這些結果並沒有經過重複驗證，且有5個大型試驗的數據仍在等待被發表，需要等到所有試驗結果都被公開後，這個氣喘治療方法的價值才能被確認。