Discontinuation Schedule of Inhaled Corticosteroids in Patients With Chronic Obstructive Pulmonary Disease
Background: Long-term use of inhaled corticosteroids (ICSs) is associated with several potential adverse effects. While patients unlikely to benefit should stop ICS use, abrupt discontinuation may result in an increased risk of chronic obstructive pulmonary disease (COPD) exacerbation. Stepwise tapering may reduce this risk but data are limited, and there is no consensus on the likelihood of COPD exacerbations following ICS discontinuation. The North Texas Veterans Affairs Health Care System conducted a single center, retrospective cohort study to evaluate the rate of COPD exacerbations following the discontinuation of ICS therapy using different schedules of discontinuation.
Methods: Data were collected from the electronic health records of patients aged ≥ 40 years with a diagnosis of COPD who were on a stable dose of an ICS for ≥ 1 year that was subsequently discontinued with a last documented fill date between January 10, 2021 and September 1, 2021. Eligible patients were followed for COPD exacerbations that resulted in hospitalization until November 1, 2022. Descriptive statistics were used to evaluate characteristics of patients who experienced an exacerbation.
Results: Seventy-five patients were included: 5 (7%) experienced an exacerbation following ICS discontinuation. Age, sex, race, and ethnicity were similar for those patients who did vs did not have an exacerbation. Unexpectedly, the mean baseline eosinophil count for patients with an exacerbation was 92 cells/µL compared with 227.4 cells/µL for those without an exacerbation. Nine patients had their ICS tapered gradually, and none of them experienced an exacerbation.
Conclusions: Study findings suggest that there is a relatively low risk of COPD exacerbation following ICS discontinuation, regardless of whether a taper was performed. This result may indicate that it is reasonable to abruptly discontinue ICS in eligible patients.
Limitations
The small sample size, resulting from the strict exclusion criteria, limits the generalizability of the results. Although the low number of events seen in this study supports safety in ICS discontinuation, there may have been higher rates observed in a larger population. The most common reason for patient exclusion was the initiation of another ICS immediately following discontinuation of the original ICS. During the study period, VANTHCS underwent a change to its formulary: Fluticasone/salmeterol replaced budesonide/formoterol as the preferred ICS/LABA combination. As a result, many patients had their budesonide/formoterol discontinued during the study period solely to initiate fluticasone/salmeterol therapy. As these patients did not truly have their ICS discontinued or have a significant period without ICS therapy, they were not included in the results, and the total patient population available to analyze was relatively limited.
The low event rate also limits the ability to compare various factors influencing exacerbation risk, particularly taper vs abrupt ICS discontinuation. This is further compounded by the small number of patients who had a taper performed and the lack of consistency in the method of tapering used. Statistical significance could not be determined for any outcome, and all findings were purely hypothesis generating. Finally, data were only collected for moderate or severe COPD exacerbations that resulted in an emergency department visit or hospitalization, so there may have been mild exacerbations treated in the outpatient setting that were not captured.
Despite these limitations, this study adds data to an area of COPD management that currently lacks strong clinical guidance. Since investigators had access to clinician notes, we were able to capture ICS tapers even if patients did not receive a prescription with specific taper instructions. The extended follow-up period of 12 months evaluated a longer potential time to impact of ICS discontinuation than is done in most COPD clinical trials.
Conclusions
Overall, very low rates of COPD exacerbations occurred following ICS discontinuation, regardless of whether a taper
