Biological Therapy for Chronic Obstructive Pulmonary Disease (COPD): Efficacy and Safety

Background: The predominant airway inflammation in chronic obstructive pulmonary disease (COPD) is neutrophilic, although numerous studies have shown that eosinophilic inflammation contributes significantly to COPD. Eosinophilic COPD patients are characterized by a greater number of total exacerbations and higher hospitalization rates. Biological therapy targets multiple steps in eosinophilic inflammation, providing a promising approach to reduce exacerbation frequency and mortality. Objective: To provide a timely, rigorous, and continuously updated summary of the evidence available on the role of biological therapy for the treatment of patients with COPD. Design : This is a Living Evidence synthesis, that starts with a baseline synthesis report of the effects of the intervention on the main predefined outcomes. Based on its conclusions, we will set up the living evidence approach, and the evidence monitoring will begin. Methods: Evidence identification, screening, and selection. Automated living searches were performed in relevant databases following the Epistemonikos procedures. Results were incorporated into the Epistemonikos Living OVerview of Evidence (L.OVE) platform which was used for evidence screening, and selection. Two reviewers screened all titles and abstracts supported by the platform automated classifiers that excluded references with a low probability of being relevant. For this baseline report we included randomized trials that evaluated the use of biological therapy compared to the use of standard-of-therapy alone in adult patients with COPD. Main outcomes defined as critical or important for decision making include exacerbation rate, exacerbation-free time, lung function and quality of life. Two reviewers independently screened each study for eligibility, extract data, and assess its methodological quality using appropriate tools. We performed meta-analyses of the studys results when pertinent. We applied the GRADE approach to assess the certainty of the evidence found for each outcome. We will continuously monitor the evidence by performing daily searches and monthly screening of the retrieved references. Additionally, each three months we will manually search for ongoing studies in the International Clinical Trials Registry Platform trial registries. The evidence monitoring, including decisions to incorporate evidence and withdraw the question from the living mode will follow the process proposed by the Living Evidence to Inform Health Decisions framework as stated in our protocol. A living, web-based version of this review will be openly available during the next year. We will resubmit it every time the conclusions change or whenever there are substantial updates. Results Initial searches retrieved 24 systematic reviews, 2 evaluating the use of biologics on COPD, which included 6 randomized control trials. Additional searches retrieved 125 randomized controlled trials (RCTs). Of these, 31 RCTs were deemed potentially eligible and were reviewed in full text. Ultimately, 9 RCTs evaluating the use of biological therapies (MEDI8968, benralizumab, mepolizumab, dupilumab, astegolimab, and itepekimab) compared to placebo in COPD patients were included. The GRADE quality of evidence for the main outcomes was assessed as intermediate. Conclusions: The evidence suggests that biological therapies may reduce the risk of exacerbations in patients with chronic obstructive pulmonary disease (COPD). However, the overall impact on lung function and quality of life remains inconclusive. The variability in study outcomes, particularly concerning SGRQ scores and FEV1, emphasizes the need for continuing monitoring evidence.