Systematic review of inhaled corticosteroid withdrawal effects in chronic obstructive pulmonary disease, and comparison with two “real-life” studies

Chronic obstructive pulmonary disease (COPD) is common and preventable. The long-term safety of inhaled corticosteroid (ICS) use in COPD is still unclear and requires further investigation. This systematic review aimed to determine the effect of withdrawal of ICS use in COPD by examining randomized controlled trials (RCTs) and comparing their findings with those of “real-life” studies. Two independent reviewers searched for RCTs in the PubMed, EMBASE, and Cochrane databases and in CINAHL. Searches were conducted by using controlled vocabulary and free-text aliases for corticosteroids, COPD, and RCTs in each database. Data extraction was also conducted by the two reviewers. The main outcomes were exacerbations, lung function, health-related quality of life, symptoms, and exercise capacity. To assess the effect of ICS withdrawal more comprehensively, we also searched for “real-life” studies, and explored the reasons for different results among different trials. We located five RCTs, which met the inclusion criteria, and two “real-life” studies. Due to definitional and other discrepancies among trials, we could not perform a meta-analysis. In the RCTs, exacerbation was reported as an outcome in four out of five RCTs. Only one study showed that the risk of exacerbation did not increase after ICS withdrawal. Decrease in lung function from baseline was found in the withdrawal group in four trials, but only three trials found a statistically significant difference. All five trials compared differences in health-related quality of life. Two trials did not find significant changes, while a small but statistically significant difference in favor of the ICS group was observed in the other trials. In contrast, in the two real-life studies, no differences in forced expiratory volume in the first second (FEV1) values and exacerbation rate were observed between patients who were and were not withdrawn from ICS treatment. We concluded that the effect of ICS withdrawal on patients with COPD may be dependent on disease severity, use of background long-acting bronchodilator medication, and whether COPD is combined with airway hyper-responsiveness, among other factors.