Anti-leukotriene agents compared to inhaled corticosteroids in the management of recurrent and/or chronic asthma in adults and children

 

Abstract

Background

Anti-leukotrienes agents are currently being studied as alternative first line agents to inhaled corticosteroids in mild to moderate chronic asthma.

Objectives

To compare the safety and efficacy of anti-leukotriene agents with inhaled glucocorticoids (ICS) and to determine the dose-equivalence of anti-leukotrienes to daily dose of ICS.

Search methods

We searched MEDLINE (1966 to Aug 2003), EMBASE (1980 to Aug 2003), CINAHL (1982 to Aug 2003), the Cochrane Airways Group trials register, and the Cochrane Central Register of Controlled Trials (August 2003), abstract books, and reference lists of review articles and trials. We contacted colleagues and international headquarters of anti-leukotrienes producers.

Selection criteria

Randomised controlled trials that compared anti-leukotrienes with inhaled corticosteroids during a minimal 30-day intervention period in asthmatic patients aged 2 years and older.

Data collection and analysis

Two reviewers independently assessed the methodological quality or trials and extracted trial data. The primary outcome was the rate of exacerbations requiring systemic corticosteroids. Secondary outcomes included lung function, indices of chronic asthma control, adverse effects and withdrawal rates.

Main results

27 trials (including 1 trial testing two protocols) met the inclusion criteria; 13 were of high methodological quality; 20 are published in full-text. All trials pertained to patients with mild to moderate persistent asthma. Only 3 trials focused on children and adolescents. Trial duration varied from 4 to 37 weeks. In most trials, daily dose of ICS was 400 mcg of beclomethasone or equivalent. Patients treated with anti-leukotrienes were 65% more likely to suffer an exacerbation requiring systemic steroids [Relative Risk 1.65; 95% Confidence Interval (CI) 1.36 to 2.00]. Twenty six (95% CI: 17 to 47) patients must be treated with anti-leukotrienes instead of inhaled corticosteroids to cause one extra exacerbation. Significant differences favouring ICS were noted in secondary outcomes where the improvement in FEV1 reached 130 mL [13 trials; 95% CI: 50, 140 mL ]. Other significant benefits of ICS were seen for symptoms, nocturnal awakenings, rescue medication use, symptom-free days, and quality of life. Anti-leukotriene therapy was associated with 160% increased risk of withdrawals due to poor asthma control. Twenty nine (95% CI 20 to 48) patients must be treated with anti-leukotrienes instead of inhaled corticosteroids to cause one extra withdrawal due to poor control . Risk of side effects was not different between groups.

Authors' conclusions

Inhaled steroids at a dose of 400 mcg/day of beclomethasone or equivalent are more effective than anti-leukotriene agents given in the usual licensed doses. The exact dose-equivalence of anti-leukotriene agents in mcg of ICS remains to be determined. Inhaled glucocorticoids should remain the first line monotherapy for persistent asthma.

 

Plain language summary

Anti-leukotriene agents compared to inhaled corticosteroids for people with asthma

In an asthma attack, the airways (passages to the lungs) narrow from muscle spasms and swelling (inflammation), which can cause breathing problems, wheezing and coughing. Inhaled corticosteroid drugs are used to reduce the swelling of the airways in people with asthma. Anti-leukotrienes are a new class of anti-inflammatory drugs that may have fewer adverse effects than inhaled corticosteroids. The review suggests that this class of drug is safe but it is slightly less effective than a low dose of inhaled corticosteroids. More research is needed to determine its efficacy in children.

 

摘要

背景

比較抗白三烯(antileukotriene)劑和吸入型皮質類固醇在成人和兒童的再發性和/或慢性氣喘的治療

抗白三烯劑是目前正在研究的一種藥物，用來替代吸入型皮質類固醇，作為輕度到中度慢性氣喘的第一線治療。

目標

比較抗白三烯劑和吸入型皮質類固醇的安全性和療效，並確定抗白三烯劑相對於吸入型皮質類固醇每日劑量的劑量當量。

搜尋策略

搜尋MEDLINE (1966到2003年8月)、EMBASE (1980到2003年8月)、CINAHL (1982到2003年8 月)、Cochrane Airways Group trials register和 Cochrane Central Register of Controlled Trials (2003 年8月)、摘要書籍和納入文章及試驗的參考資料表。聯絡製造抗白三烯劑的同行及其國際總部。

選擇標準

對2歲及以上年齡的氣喘患者，比較抗白三烯劑和吸入型皮質類固醇治療至少三十天的隨機對照試驗。

資料收集與分析

兩位審查員各自評估納入研究的方法學品質，並擷取數據。主要結果為發作時需要全身性皮質類固醇的比例。次要結果包括肺功能、慢性氣喘控制指標、副作用和退出率等。

主要結論

二十七個試驗(包括一項檢測兩個草案的試驗)符合納入標準。十三個研究的方法學品質良好，二十個有全文發表。所有試驗納入的都是輕度到中度持續性氣喘的患者。只有三個是針對兒童和青少年。研究時間從四週到37週。大部分研究中所使用的吸入型皮質類固醇為每日劑量400mcg的beclomethasone或相當藥物。接受抗白三烯劑治療者，發生需要使用全身性皮質類固醇的急性發作比例較高(相對風險：1.65；95%信賴區間1.36到 2.00)。以抗白三烯劑取代吸入型類固醇時，每治療二十六位(95%信賴區間17到47)病患，就會多一次發作。在次要結果方面，明顯支持使用吸入型皮質類固醇，其中FEV1改善達130毫升(13個試驗；95%信賴區間50到140 毫升)。吸入型皮質類固醇在包括症狀、夜間醒來、急救藥物的使用、無症狀天數和生活品質等各方面也有明顯的效益。由於氣喘控制不良，抗白三烯劑治療組的中途退出率明顯增加160%。以抗白三烯劑取代吸入型類固醇時，每治療二十九位(95%信賴區間20到48)病患，就會因為氣喘控制不良而多一個退出。副作用的風險兩組間沒有差別。

作者結論

Beclomethasone 400 mcg/日或相當藥物劑量的吸入型皮質類固醇，比核准劑量的抗白三烯劑來得有效。抗白三烯劑相對於吸入型皮質類固醇的正確劑量當量(mcg)尚待確認。吸入型類固醇仍是持續性氣喘的第一線單一治療藥物。

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

抗白三烯劑是一種新型抗發炎藥，可以幫助控制氣喘症狀。證據顯示，雖然它們是安全的，但療效卻不如低劑量(400 mcg/日)的吸入型皮質類固醇 (beclomethasone dipropionate或相當藥物)。當氣喘發作時，呼吸道 (通到肺的管道) 因肌肉痙攣和腫脹 (發炎) 變狹窄，因而造成呼吸困難、哮喘和咳嗽。吸入型皮質類固醇在氣喘患者身上可以減少呼吸道的腫脹。抗白三烯劑是一種新型抗發炎藥，副作用可能比吸入型皮質類固醇少。本回顧結果顯示，這類藥物是安全的，但療效比低劑量吸入型皮質類固醇稍差。至於在兒童的使用效果，則需要進多的研究確認。