Triple Therapy De-Escalation and Withdrawal of Inhaled Corticosteroids to Dual Bronchodilator Therapy in Patients with Chronic Obstructive Pulmonary Disease (COPD): A Systematic Review and Meta-Analysis

: Background/Objectives: The interpretation of evidence on the de-escalation of triple therapy with the withdrawal of inhaled corticosteroids (ICSs) to dual bronchodilator therapy with a long-acting muscarinic antagonist (LAMA) and a long-acting beta-agonist (LABA) in patients with chronic obstructive pulmonary disease (COPD) is conflicting. We evaluated the efficacy and safety of ICS discontinuation from LABA-LAMA-ICS triple therapy compared to its continuation. Methods: We searched PubMed, Embase, Scopus, Web Of Science, clinicaltrial.gov, and CENTRAL for RCTs and observational studies from inception to 22 March 2024, investigating the effect of triple therapy de-escalation with the withdrawal of ICSs to dual therapy on the risk of COPD exacerbation, pneumonia, and lung function. This study was registered with PROSPERO, CRD42024527942. Results: A total of 3335 studies was screened; 3 RCTs and 3 real-world non-interventional studies were identified as eligible. The analysis of the time to the first moderate or severe exacerbation showed a pooled HR of 0.96 (95% CI, 0.80-1.15; I2 = 77%) for ICS withdrawal compared to triple therapy continuation. The analysis according eosinophil levels showed that COPD subjects with ≥300 eosinophils/µL had a significant increase in the incidence of moderate or severe exacerbations when de-escalated to LABA/LAMA (pooled HR: 1.35, 95% CI: 1.00-1.82; I2: 56%). ICS withdrawal did not significantly affect the risk of mortality and pneumonia. Conclusions: The de-escalation of triple therapy with ICS withdrawal does not affect the main outcomes evaluated (moderate or severe exacerbations, change in trough FEV1). COPD patients with high blood eosinophils (≥2% or ≥300 cells/µL) are most likely to benefit from continuing triple therapy.