Abstract
Inhaled corticosteroids (ICS) reduce COPD exacerbation frequency and slow decline in health related quality of life but have little effect on lung function, do not reduce mortality, and increase the risk of pneumonia. We systematically reviewed trials in which ICS have been withdrawn from patients with COPD, with the aim of determining the effect of withdrawal, understanding the differing results between trials, and making recommendations for improving methodology in future trials where medication is withdrawn. Trials were identified by two independent reviewers using MEDLINE, EMBASE and CINAHL, citations of identified studies were checked, and experts contacted to identify further studies. Data extraction was completed independently by two reviewers. The methodological quality of each trial was determined by assessing possible sources of systematic bias as recommended by the Cochrane collaboration. We included four trials; the quality of three was adequate. In all trials, outcomes were generally worse for patients who had had ICS withdrawn, but differences between outcomes for these patients and patients who continued with medication were mostly small and not statistically significant. Due to data paucity we performed only one meta-analysis; this indicated that patients who had had medication withdrawn were 1.11 (95% CI 0.84 to 1.46) times more likely to have an exacerbation in the following year, but the definition of exacerbations was not consistent between the three trials, and the impact of withdrawal was smaller in recent trials which were also trials conducted under conditions that reflected routine practice. There is no evidence from this review that withdrawing ICS in routine practice results in important deterioration in patient outcomes. Furthermore, the extent of increase in exacerbations depends on the way exacerbations are defined and managed and may depend on the use of other medication. In trials where medication is withdrawn, investigators should report other medication use, definitions of exacerbations and management of patients clearly. Intention to treat analyses should be used and interpreted appropriately.
Highlights
The mortality, morbidity and economic burden of Chronic Obstructive Pulmonary Disease (COPD) exacerbations is well documented [1,2,3,4]
It is recognised that Inhaled corticosteroids (ICS) in stable COPD are associated with an increased risk of pneumonia [8], and the long-term use of high-dose ICS has been associated with adverse effects including cataracts [9], glaucoma [10] and osteoporosis [11]
UK National Institute of Health and Clinical Excellence (NICE) guidance discourages the use of ICS as monotherapy, but does encourage their use with bronchodilators if patients have moderate or severe COPD and are still symptomatic, or are experiencing two or more exacerbations requiring treatment per year [3]
Summary
The mortality, morbidity and economic burden of Chronic Obstructive Pulmonary Disease (COPD) exacerbations is well documented [1,2,3,4]. Reduction in the frequency of exacerbations is a major therapeutic aim in COPD and treatment with inhaled corticosteroids (ICS) has been associated with a 25% reduction in exacerbations [5]. In a Cochrane review by Yang, ICS were found both to reduce the frequency of COPD exacerbations by 0.26 per patient per year (weighted mean difference: 95% CI -0.37 to -0.14) and to slow the rate of decline in health related quality of life as determined by the St George’s Respiratory Questionnaire (weighted mean difference: -1.22 units/year, 95% CI -1.83 to -0.60) [6]. UK National Institute of Health and Clinical Excellence (NICE) guidance discourages the use of ICS as monotherapy, but does encourage their use with bronchodilators if patients have moderate or severe COPD and are still symptomatic, or are experiencing two or more exacerbations requiring treatment per year [3]
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