Effect of different corticosteroid regimes for hospitalised patients with exacerbated COPD: pooled analysis of individual participant data from the REDUCE and CORTICO-COP trials

Abstract

Background Systemic corticosteroid administration for severe acute exacerbations of COPD (AECOPD) reduces the duration of hospital stays. Corticosteroid-sparing regimens have showed non-inferiority to higher accumulated dose regimens regarding re-exacerbation risk in patients with AECOPD. However, it remains unclear whether 14-day or 2–5-day regimens would result in shorter admission durations and changes in mortality risk. We explored this by analysing the number of days alive and out of hospital based on two randomised controlled trials with different corticosteroid regimens. Methods We pooled individual patient data from the two available multicentre randomised trials on corticosteroid-sparing regimens for AECOPD: the REDUCE (n = 314) and CORTICO-COP (n = 318) trials. In the 14-day regimen group, patients were older, fewer patients received pre-treatment with antibiotics and more patients received pre-treatment with systemic corticosteroids. Patients randomly allocated to the 14-day and 2–5-day regimens were compared, with adjustment for baseline differences. Results The number of days alive and out of hospital within 14 days from recruitment was higher for the 2–5 day regimen group (mean 8.4 days; 95% confidence interval [CI] 8.0–8.8) than the 14-day regimen patient group (4.2 days; 95% CI3.4–4.9; p < 0.001). The 14-day AECOPD group had longer hospital stays (mean difference, 5.4 days [standard error ± 0.6]; p < 0.0001) and decreased likelihood of discharge within 30 days (hazard ratio [HR] 0.5; 95% CI 0.4–0.6; p < 0.0001). Comparing the 14-day regimen and the 2–5 day regimen group showed no differences in the composite endpoint ‘death or ICU admission’ (odds ratio [OR] 1.4; 95% CI 0.8–2.3; p = 0.15), new or aggravated hypertension (OR 1.5; 95% CI 0.9–2.7; p = 0.15), or mortality risk (HR 0.8; 95% CI 0.4–1.5; p = 0.45) during the 6-month follow-up period. Conclusion 14-day corticosteroid regimens were associated with longer hospital stays and fewer days alive and out of hospital within 14 days, with no apparent 6-month benefit regarding death or admission to ICU in COPD patients. Our results favour 2–5 day regimens for treating COPD exacerbations. However, prospective studies are needed to validate these findings.

Duration and dosing of systemic corticosteroids for acute exacerbation of COPD, protocol for a systematic review with meta-analysis of randomized trials and cohort studies

“…This will be an updated systematic review and meta-analyses of both RCTs and cohort studies to assess the efficacy and safety of short versus long duration and low versus high dosage of corticosteroid treatment for COPD exacerbations. Even though a shorter course of 5–7 days of corticosteroid administration has been established as noninferior to a longer course of treatment, these decisions were based on limited data and meta-analyses that included RCTs only [ 8 , 9 ]. Additionally, the optimal dosing regimen for corticosteroid treatment still remains unclear.…”

“…We will include any corticosteroid treatment given to alleviate COPD exacerbation, via any administration method including but not limited to oral, intravenous, or mixed administration. We define short course of corticosteroid administration to be ≤ 7 days and long course to be >7 days based on previous studies and meta-analyses [ 8 , 9 ]. In our exploratory searches on dosage studies, there have been significant heterogeneity between studies in their definition of low vs high corticosteroid dosage.…”

“…Systemic steroids have been shown to reduce airway inflammations and pulmonary edema during exacerbations, thereby alleviating the clinical symptoms for patients. However, corticosteroids can also cause many significant side effects, such as fluid retention, osteoporosis, hyperglycemia, and increased risk for opportunistic infections [ 5 , 8 , 9 ]. The extent of both therapeutic and adverse effects of corticosteroid treatment is directly associated with the duration and dose of its administration.…”

β-Cyclodextrin Inclusion Complexes of Budesonide with Enhanced Bioavailability for COPD Treatment

“…Pharmacologic management of COPD aims for the reduction of the current symptoms and future exacerbation risks [3]. Treatment of the disease is conducted with inhaled bronchodilators, corticosteroids [4], or long-acting beta-agonists. If the patients have severe symptoms or intense exacerbations, combination therapy has been recommended because it lowers the incidence of exacerbations [3,5].…”

“…Cyclodextrins (CDs) are cyclic oligosaccharides consisting of glucopyranosyl units linked with α- (1,4) bonds [11]. The natural CDs α-, β-, and γ-CDs are composed of 6, 7, and 8 glucose units, respectively [12].…”