Meta-Analysis of Randomized, Controlled Trials Assessing the Effectiveness and Safety of Biological Treatments in Chronic Obstructive Pulmonary Disease Patients

Abstract

Anti-interleukin-5 (IL-5), anti-IL-5 receptor and anti-interleukin-4 (IL-4) have emerged as potential treatments for severe eosinophilic asthma, yet their role in treating chronic obstructive pulmonary disease (COPD) is unclear. A literature review was conducted up to May 31, 2024. Only randomized controlled trials (RCTs) assessing the clinical efficacy and adverse effects of biological treatment (anti-IL-5/ anti-IL-5 receptor /anti-IL-4) in COPD patients were included in this meta-analysis. Primary outcomes focused on COPD exacerbation risk, with secondary outcomes examining lung function, quality of life, and adverse events. Four articles comprising 6 RCTs were analyzed. Among 2837 patients receiving anti-IL-5/anti-IL-5 receptor therapies, 468 receiving anti-IL-4 therapies, and 1913 receiving placebo. Overall, biological treatment therapies collectively demonstrated a reduced risk of COPD exacerbation compared to placebo (rate ratio, 0.88; 95% CI, 0.80–0.97, I² = 53%). Specifically, dupilumab statistically significant reduction in exacerbation risk (rate ratio 0.70, 95% CI 0.58–0.84). Benralizumab showed a borderline reduction in exacerbation risk (rate ratio, 0.92; 95% CI, 0.85–1.00, I² = 0%, while Mepolizumab exhibited a trend towards lower exacerbation risk that did not reach statistical significance (rate ratio 0.90, 95% CI 0.77–1.06, I² = 62%). Subgroup analysis showed that patients with COPD and eosinophils ≥300 per cubic millimeter who received biological treatment may experience a reduced risk of acute exacerbation. Changes in lung function from baseline did not significantly differ between biological therapies and placebo. Analysis of St. George's Respiratory Questionnaire (SGRQ) scores indicated significant improvements with biological therapies compared to placebo (mean difference -1.30, 95% CI -2.46 to -0.14, I² = 28%). Biological therapies showed comparable risks of adverse events compared to placebo. This meta-analysis suggests that biological therapies may reduce the risk of acute exacerbations and improve quality of life in COPD patients compared to placebo. However, these therapies did not demonstrate significant improvements in pulmonary function. Future studies are needed to delineate the role of these biologic therapies in managing COPD exacerbations.