Clinical and Economic Impact of Long-Term Inhaled Corticosteroid Withdrawal in Patients with Chronic Obstructive Pulmonary Disease Treated with Triple Therapy in Spain

Abstract

Purpose To determine the clinical and economic impact of inhaled corticosteroid (ICS) withdrawal in Spanish patients with COPD receiving triple therapy (TT) with ICS, long-acting β 2 -agonist (LABA), and long-acting muscarinic antagonist (LAMA). Patients and Methods This was an observational, retrospective study of BIG-PAC database medical records. Patients aged ≥40 years receiving TT from 2016 to 2018 were followed for 1 year. Two cohorts were identified: patients continuing TT (ICS+LABA+LAMA), and patients receiving TT with ICS withdrawn (LABA+LAMA). Variables included medication, exacerbations (moderate and severe), pneumonia, mortality, health resource use (HRU), and cost per patient/year. Cohorts were compared using propensity score matching (PSM). Multivariate statistical analysis using analysis of covariance and Cox proportional risks was conducted. Results Of 6541 patients included, 5740 (87.8%) continued TT and 801 (12.2%) had ICS withdrawn. Patients with ICS withdrawal were younger, had lower disease burden, higher ICS doses, and more exacerbations compared with those continuing ICS. PSM matched 795 patients in each cohort. Mean age was 68.5 years (SD: 11.2), 69.9% were male, and mean Charlson index was 2.0. Patients with ICS withdrawal had more total exacerbations in the 12 months following withdrawal compared with patients continuing TT (36.6% vs 31.4%; p=0.030). No significant differences were found for pneumonia (3.3% vs 3.6%; p=0.583) and mortality (9.9% vs 7.5%; p=0.092). Median time to first exacerbation was shorter in patients with ICS withdrawal compared with those continuing ICS (HR: 0.69, 95% CI: 0.57–0.83; p<0.001). Mean health cost per patient/year among patients with ICS withdrawal was higher than those continuing TT (€2993 vs €2130; p<0.001). Conclusion ICS withdrawal in patients with COPD receiving TT was associated with increased exacerbations, HRU, and costs compared with continuing TT, with health and economic impacts on patients and the Spanish National Healthcare System, respectively. Pneumonia and mortality rates were similar between groups.

Withdrawal of Inhaled Corticosteroids from Patients with COPD; Effect on Exacerbation Frequency and Lung Function: A Systematic Review

“…One observational study did report a worsening in exacerbation rate among those who withdrew from ICS therapy. 15 These participants had less severe airflow limitation at baseline and fewer prior exacerbations compared to those in the continuation group.…”

“… Withdrawal arm: FEV 1 % pred 58.2% ± 20.9% Steroid arm: 53.9% ± 22.5% Withdrawal arm: 1.1 ± 1.4 Steroid arm: 1.1 ± 1.4 ≥2 fixed dose ICS/LABA and separate LAMA prescriptions, or ≥2 fixed dose ICS/LABA/LAMA prescriptions, in the prior year Unscheduled hospital admission or A&E attendance for COPD/respiratory condition or generic hospitalisation code on same day as a lower respiratory coded consultation, course of oral steroids and/or antibiotics prescribed with lower respiratory consultation. Neches Garcia 2022 15 Retrospective observational study using records from the BIG-PAC administrative database. 1 year follow-up.…”

“… Annual exacerbation rate (mean (SD)): 1.01 (±1.46) per patient year in withdrawal vs 0.94 (±1.41) per patient year in steroid arm (p>0.05) No significant difference in annualised change in FEV 1 (mean (SD)) between trial arms: -0.049L (±0.23) withdrawal vs −0.019L (±0.25) steroid arm (p>0.05) 61.9% in withdrawal arm. Neches Garcia 2022 15 LABA/ICS/LAMA vs LABA/LAMA. Increased exacerbations in withdrawal vs steroid arm.…”

“…[32][33][34] Neches Garcia et al found an increase in the annual exacerbation rate within the ICS withdrawal in comparison to the ICS continuation group. 15 The results of the quality assessment of the observational studies are presented in Table S8. Five of the six studies were of high quality.…”

“…13 Despite the increasing evidence for the safety and feasibility of ICS withdrawal and its prominence in clinical guidelines, 9,12,14 a number of recent studies suggest that the intervention may lead to a deterioration in clinical outcomes. 15,16 In addition, little is known of the participants who fail a trial of withdrawal. The primary aim of this systematic review was to examine the effect of ICS withdrawal on the exacerbation frequency and change in lung function (FEV 1 ) of COPD patients.…”