Withdrawal of inhaled corticosteroids in COPD: A meta-analysis
Introduction
The impact of inhaled corticosteroid (ICS) discontinuation in chronic obstructive pulmonary disease (COPD) has been investigated in several randomized clinical trials (RCTs) and real life studies since 2001. Nevertheless, to date conflicting findings and opinions remain on the real benefit of withdrawal of ICS. In fact, while several RCTs reported that COPD patients may be at increased risk of exacerbation, deterioration of quality of life and lung function after ICS discontinuation [1], [2], [3], [4], the data from two real life studies indicated that withdrawal of ICS can be safe and with no increased risk of exacerbations [5], [6]. Conversely, the results of a large RCT indicated that the risk exacerbations was similar among COPD patients who discontinued ICS and those who continued glucocorticoid therapy [7], whereas an observational prospective study concluded that ICS discontinuation can worsen lung function decline, airway hyperresponsiveness and quality of life [8]. Reassurance in ICS withdrawal was further provided by another RCT that enrolled low exacerbation risk patients [9].
ICS are widely prescribed across all the levels of COPD severity and exacerbation risk, with a rate of over-prescription that is two fold higher than that expected by following guidelines or recommendations such as the Global Initiative for Chronic Obstructive Lung Diseases (GOLD), although since 2007 it was suggested to limit the use of ICS in patients with reduced lung function and/or high exacerbation rate [10]. Nevertheless, the last version of the GOLD recommendation (2017) has highlighted that the studies on withdrawal of ICS produced equivocal results, and suggested that differences among the studies may be related with differences in methodology [11].
In this confusing scenario, we have carried out a quantitative synthesis via meta-analysis of the currently available data in order to provide consistent and homogeneous findings that may help to better clarify the real impact of ICS discontinuation in COPD patients, especially with regards to the risk of exacerbation, lung function and quality of life.
Section snippets
Materials and methods
Detailed meta-analytic methods are reported in the online Supplemental Materials.
Studies characteristics
Results obtained from 6066 COPD patients were selected from 10 published studies Table 1 [1], [2], [3], [4], [5], [6], [7], [8], [9], [22]. Table 2 shows the definition of exacerbation as reported by analyzed. Further results are reported in the online Supplemental Materials.
Primary endpoints
Overall, the withdrawal of ICS did not significantly (P > 0.05) affect the risk of COPD exacerbations. However, the subset analysis including only RTCs shown that, although in a non-significant manner (P > 0.05), there was
Discussion
The results of this meta-analysis demonstrates that ICS withdrawal did not significantly increase neither the overall risk of COPD exacerbation, nor the risk of moderate-to-severe exacerbations, although the time to the first exacerbation was significantly shorter in patients who discontinued ICS compared to those who continued the treatment. However, a signal of higher risk of experiencing at least one exacerbation was detected in patients enrolled in RCTs who discontinued ICS. Furthermore,
Conclusions
Although the current large body of evidence available from both RTCs and real life studies, even a large and rigorous meta-analysis did not allow to bridge the scientific gap concerning the discontinuation of ICS in COPD. This study highlights the strong clinical need of well designed studies aimed to investigate the impact of ICS withdrawal by clustering CODP patients with regard to at least the phenotype characteristics (i.e. frequent exacerbator, emphysema-hyperinflation and COPD with an
Question
Does withdrawal of ICS impair the risk of exacerbation, lung function and quality of life of COPD patients?
Findings
ICS withdrawal did not significantly increase the overall rate of COPD exacerbation, although a clinically important increased risk of severe exacerbation was detected. ICS withdrawal significantly impaired both lung function and quality of life, although in a non-clinically important manner.
Meaning
High-quality evidences concerning the impact of ICS withdrawal in COPD.
Guarantor
LC and PR have the responsibility for the content of the manuscript, including the data and analysis.
Author contributions
LC and PR contributed to study conception and design; contributed to acquisition, analysis, and interpretation of data; drafted the submitted article and revised it critically for important intellectual content and provided final approval of the version to be published.
MGM and MCa contributed to study design; contributed to interpretation of data; drafted the submitted article and revised it
Sources
This study was supported by institutional funds (University of Rome “Tor Vergata”, Rome, Italy).
Sponsor
Not applicable.
Role of sponsor/funder
No sponsor/funder had a role in the design of the study, the collection and analysis of the data, or in the preparation of the manuscript.
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