Inhaled corticosteroids (ICSs) are frequently prescribed for the treatment of chronic obstructive pulmonary disease (COPD) to reduce exacerbations in a specific subset of patients. The long-term use of ICSs, however, is associated with several potential systemic adverse effects, including adrenal suppression, decreased bone mineral density, and immunosuppression.1 The concern for immunosuppression is particularly notable and leads to a known increased risk for developing pneumonia in patients with COPD. These patients frequently have other concurrent risk factors for pneumonia (eg, history of tobacco use, older age, and severe airway limitations) and are at higher risk for more severe outcomes in the setting of pneumonia.2,3
Primarily due to the concern of pneumonia risks, the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines have recommended ICS discontinuation in patients who are less likely to receive significant benefits from therapy.4 Likely due to an anti-inflammatory mechanism of action, ICSs have been shown to reduce COPD exacerbation rates in patients with comorbid asthma or who have evidence of a strong inflammatory component to their COPD. The strongest indicator of an inflammatory component is an elevated blood eosinophil (EOS) count; those with EOS > 300 cells/µL are most likely to benefit from ICSs, whereas those with a count < 100 cells/µL are unlikely to have a significant response. In addition to the inflammatory component consideration, prior studies have shown improvements in lung function and reduction of exacerbations with ICS use in patients with frequent moderate-to-severe COPD exacerbations.5 Although the GOLD guidelines provide recommendations about who is appropriate to discontinue ICS use, clinicians have no clear guidance on the risks or the best discontinuation strategy.
Based primarily on data from a prior randomized controlled trial, the Veterans Integrated Services Network (VISN) 17, which includes the Veterans Affairs North Texas Health Care System (VANTHCS) in Dallas, established a recommended ICS de-escalation strategy.6,7 The strategy included a 12-week stepwise taper using a mometasone inhaler for all patients discontinuing a moderate or high dose ICS. The lack of substantial clinical trial data or expert consensus guideline recommendations has left open the question of whether a taper is necessary. To answer that question, this study was conducted to evaluate whether there is a difference in the rate of COPD exacerbations following abrupt discontinuation vs gradual taper of ICS therapy.
Methods
This single-center, retrospective cohort study was conducted at VANTHCS. Patient electronic health records between January 10, 2021, and September 1, 2021, were reviewed for the last documented fill date of any inhaler containing a steroid component. This time frame was chosen to coincide with a VANTHCS initiative to follow GOLD guidelines for ICS discontinuation. Patients were followed for outcomes until November 1, 2022.
To be included in this study, patients had to have active prescriptions at VANTHCS, have a documented diagnosis of COPD in their chart, and be prescribed a stable dose of ICS for ≥ 1 year prior to their latest refill. The inhaler used could contain an ICS as monotherapy, in combination with a long-acting β-agonist (LABA), or as part of triple therapy with an additional long-acting muscarinic antagonist (LAMA). The inhaler needed to be discontinued during the study period of interest.
Patients were excluded if they had a diagnosis of asthma, were aged < 40 years, had active prescriptions for multiple ICS inhalers or nebulizers, or had significant oral steroid use (≥ 5 mg/d prednisone or an equivalent steroid for > 6 weeks) within 1 year of their ICS discontinuation date. In addition, to reduce the risk of future events being misclassified as COPD exacerbations, patients were excluded if they had a congestive heart failure exacerbation up to 2 years before ICS discontinuation or a diagnosis of COVID-19 infection up to 1 year before or 6 months after ICS discontinuation. Patients with a COPD exacerbation requiring an emergency department or hospital visit within 2 years prior to ICS discontinuation were also excluded, as de-escalation of ICS therapy was likely inappropriate in these cases. Finally, patients were excluded if they were started on a different ICS immediately following the discontinuation of their first ICS.
The primary outcome for this study was COPD exacerbations requiring an emergency department visit or hospitalization within 6 months of ICS discontinuation. A secondary outcome examining the rates of COPD exacerbations within 12 months also was used. The original study design called for the use of inferential statistics to compare the rates of primary and secondary outcomes in patients whose ICS was abruptly discontinued with those who were tapered slowly. After data collection, however, the small sample size and low event rate meant that the planned statistical tests were no longer appropriate. Instead, we decided to analyze the planned outcomes using descriptive statistics and look at an additional number of post hoc outcomes to provide deeper insight into clinical practice. We examined the association between relevant demographic factors, such as age, comorbidity burden, ICS potency, duration of ICS therapy, and EOS count and the clinician decision whether to taper the ICS. These same factors were also evaluated for potential association with the increased risk of COPD exacerbations following ICS discontinuation.