ICS Withdrawal Not Found to Increase Risk of COPD-Related Exacerbations

Physicians can withdraw inhaled corticosteroids (ICS) from triplet therapy without increasing patients’ risk of chronic obstructive pulmonary disease (COPD)-related exacerbations.

Withdrawing inhaled corticosteroids (ICS) from a patient’s chronic obstructive pulmonary disease (COPD) treatment regimen will not increase their risk of exacerbations under certain conditions, according to a recent study published in Respiratory Research.

The researchers said their results give more information on how ICS withdrawal affects patients with COPD generally excluded from randomized control trials such as those who are managed in primary care, who don’t have frequent exacerbations, or who have blood eosinophil concentrations below 300 cells/μL.

A common form of combination therapy for COPD is triple therapy, which consists of an ICS plus 1 or 2 inhaled bronchodilators, such as long-acting muscarinic antagonists and long-acting β2-agonists.

However, recent studies suggest that ICS are overprescribed to patients, leading the European Respiratory Society (ERS) to develop guidelines indicating conditional recommendations for the withdrawal of ICS from patients who have infrequent exacerbations. Long-term use of ICSs can also lead to higher risks of adverse effects.

“It is important to identify patients in whom the risk/benefit ratio clearly supports the use of these drugs,” wrote the investigators.

The researchers conducted their observational comparative effectiveness study by gathering longitudinal data from the United Kingdom’s Optimum Patient Care Research Database. Eligible patients had to have an index prescription date (IPD) prior to January 12, 2018, to allow for a 1-year period to analyze withdrawal outcomes.

In total, 1046 ICS cessation patients and 21,577 controls, who would continue to use an ICS, were included. Controls (4184) were matched 4:1 with cessation patients for time on triple therapy before IPD. All patients were required to be a spirometry-confirmed COPD diagnosis, be aged 40 or older, be a current or ex-smoker, have at least 1 year of continuous patient records prior to IPD, and have an ICS medication possession ratio of 70% or greater.

Overall, 76.1% of patients had 1 or fewer exacerbations during the previous year. Patients undergoing ICS cessation had a milder disease state than controls (P = .003), lower blood eosinophil concentrations (P = .006), and more respiratory consultations (P = .001) and pneumonia-coded consultations in primary care (P = .001). There were also fewer asthma diagnoses before the study baseline year (14.1% vs 26.9%; P < .001).

After controlling for confounders, patients who stopped using ICS were no more at risk of exacerbations than the control group (adjusted HR, 1.04; 95% CI, 0.94-1.15; P = .441).

During the outcome year, nearly equal amounts of the cessation (47.9%) and control groups (48.0%) experienced exacerbations.

However, the cessation group had higher rates of exacerbations managed in primary care (incidence rate ratio [IRR], 1.33; 95% CI, 1.10-1.60; P = .003) and in hospital (IRR, 1.72; 95% CI, 1.03-2.86; P = .036). The investigators said that results biasing against ICS withdrawal may have occurred due to the cessation group having more frequent exacerbations during the baseline year, which may have increased the likelihood of exacerbations during outcome year.

Additionally, patients with blood eosinophil counts equal to or greater than 300 cells/μL and who received more frequent courses of oral corticosteroids the year prior were more likely to have an exacerbation or reinitiate ICS therapy during the outcome period, resulting in unsuccessful withdrawal.

The researchers concluded that these patients should not be withdrawn from ICS treatment due to their higher risk for unsuccessful withdrawals. This falls in line with the ERS’ guidelines that recommend that patients with higher concentrations of blood eosinophils should not be taken off ICS, regardless of exacerbation history.

This study’s observational design may have been a limitation, because controlling for confounding factors may not be entirely effective, the investigators noted.


Magnussen H, Lucas S, Lapperre T. Withdrawal of inhaled corticosteroids versus continuation of triple therapy in patients with COPD in real life: observational comparative effectiveness study. Respir Res. January 21, 2020; 22(25):1-14. Doi: 10.1186/s12931-021-01615-0