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

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 study’s 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 (ref) as stated in our protocol. A living, web-based version of this review will be openly available during the next year at <ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="https://livingevidenceihd.com/lesrepo/">https://livingevidenceihd.com/lesrepo/</ext-link> . We will resubmit it every time the conclusions change or whenever there are substantial updates.

Objective

To synthesize and update evidence on the efficacy and safety of biological therapy for chronic obstructive pulmonary disease (COPD).

Methods

This living evidence synthesis included systematic reviews (SRs) and randomized controlled trials (RCTs) comparing biological therapies (e.g., benralizumab, mepolizumab, dupilumab) with placebo or standard care in adults with moderate to severe COPD. Automated searches were conducted using the Epistemonikos “Living Overview of Evidence” (L.OVE) platform, supplemented by manual searches. Two reviewers independently screened studies, extracted data, and assessed risk of bias using Cochrane RoB2 for RCTs and AMSTAR II for SRs. Meta-analyses were performed, and the certainty of evidence was evaluated using the GRADE approach.

Results

Nine RCTs were included. Biological therapy probably reduces annual exacerbation rates (moderate certainty; MD -0.12, 95% CI -0.23 to 0.00). The evidence is very uncertain about its effect on quality of life (SGRQ score: MD 0.05, 95% CI -0.04 to 0.14; very low certainty) due to serious inconsistency (I² = 95.5%) and imprecision. Biological therapy may result in little to no difference in lung function (FEV1: MD 0.02, 95% CI -0.02 to 0.06; low certainty), with serious inconsistency (I² = 76.8%) and imprecision. Biological therapy probably results in no difference in total adverse events (moderate certainty; RR 1.02, 95% CI 0.99 to 1.05) but likely reduces severe adverse events (high certainty; RR 0.84, 95% CI 0.77 to 0.93).

Conclusions

Current evidence suggests that biological therapies for COPD provide little to no clinical benefit over standard care in terms of exacerbation rates, lung function, or safety, with uncertain effects on quality of life.

Biological therapy probably has little to no effect on annual exacerbations compared with standard care.

There is likely no meaningful difference in lung function (FEV1) compared with standard care. Biologicals probably result in no difference in the number of total adverse events.

Regarding the effect on quality of life, measured by the SGRQ compared with standard care, the evidence is very uncertain; therefore, no conclusions can be drawn.

Overall, the certainty of the evidence supporting these statements is generally moderate, but is particularly limited by imprecision in estimates when considering thresholds for the minimal important difference (MID).