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Emerging biological therapies for treating chronic obstructive pulmonary disease: A pairwise and network
Paola Rogliani1, Maria Gabriella Matera2, Ermanno Puxeddu1
1Department of Experimental Medicine and Surgery, University of Rome Tor Vergata, Rome, Italy.
Abstract:
Inflammation in chronic obstructive pulmonary disease (COPD) is often corticosteroid resistant and, thus, alternative anti-inflammatory approaches are needed. Since it is still not clear whether blocking specific pro-inflammatory factors may provide clinical benefit in COPD, we have performed a meta-analysis to quantify the impact of monoclonal antibodies (mABs) targeting the cytokine/chemokine-mediated inflammation in COPD. A pairwise and network meta-analyses were performed by extracting data from randomized clicnial trials on COPD concerning the impact of mABs vs. placebo on the risk of exacerbation, forced expiratory volume in 1 s (FEV1), and St. George's Respiratory Questionnaire (SGRQ). Data on the interleukin (IL)-1β antagonist canakinumab, IL-1R1 antagonist MEDI8986, IL-5 antagonist mepolizumab, IL-5R antagonist benralizumab, IL-8 antagonist ABX-IL8, and TNF-α antagonist infliximab were found. Overall, mAB therapy had a moderate impact on the risk exacerbation, but not on FEV1 and SGRQ. The pairwise meta-analysis performed in eosinophilic patients, and the network approach, indicated that mepolizumab elicited a beneficial effect against the risk of exacerbation, whereas benralizumab was more effective in improving both FEV1 and SGRQ. This study demonstrates that targeting the pathway activated by IL-5 may have a beneficial impact in eosinophilic COPD patients.
Insights
Monoclonal antibodies targeting interleukin-5 pathways show promise for reducing exacerbations in eosinophilic chronic obstructive pulmonary disease (COPD). While some therapies improved lung function, overall benefits varied across different treatments and patient subgroups.
Area of Science:
- Pulmonary Medicine
- Immunology
- Pharmacology
Background:
- Corticosteroid resistance in chronic obstructive pulmonary disease (COPD) necessitates alternative anti-inflammatory strategies.
- The clinical efficacy of targeting specific pro-inflammatory cytokines and chemokines in COPD remains uncertain.
Purpose of the Study:
- To conduct a meta-analysis evaluating the impact of monoclonal antibodies (mABs) against cytokine/chemokine-mediated inflammation in COPD.
- To assess the effects of mABs on exacerbation risk, forced expiratory volume in 1 second (FEV1), and St. George's Respiratory Questionnaire (SGRQ) scores.
Main Methods:
- Performed pairwise and network meta-analyses of randomized clinical trials comparing mABs to placebo in COPD patients.
- Extracted data on specific mABs targeting Interleukin (IL)-1β, IL-5, and Tumor Necrosis Factor-alpha (TNF-α).
Main Results:
- Monoclonal antibody therapy demonstrated a moderate impact on reducing exacerbation risk but did not significantly improve FEV1 or SGRQ scores overall.
- Mepolizumab showed a beneficial effect on exacerbation risk in eosinophilic COPD patients.
- Benralizumab was more effective in improving both FEV1 and SGRQ scores in specific patient groups.
Conclusions:
- Targeting the IL-5 pathway offers potential benefits for managing exacerbations in eosinophilic COPD patients.
- Different monoclonal antibodies targeting inflammatory pathways may have distinct clinical effects in COPD, warranting further investigation into patient stratification.
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