Comparing the Efficacy and Safety Profile of Triple Fixed-Dose Combinations in COPD: A Meta-Analysis and IBiS Score

Paola Rogliani; Josuel Ora; Francesco Cavalli; Mario Cazzola; Luigino Calzetta

doi:10.3390/jcm11154491

Comparing the Efficacy and Safety Profile of Triple Fixed-Dose Combinations in COPD: A Meta-Analysis and IBiS Score

J Clin Med. 2022 Aug 1;11(15):4491. doi: 10.3390/jcm11154491.

Authors

Paola Rogliani^{1

2}, Josuel Ora^{1

2}, Francesco Cavalli², Mario Cazzola¹, Luigino Calzetta³

Affiliations

¹ Unit of Respiratory Medicine, Department of Experimental Medicine, University of Rome "Tor Vergata", 00133 Rome, Italy.
² Division of Respiratory Medicine, University Hospital Policlinico Tor Vergata, 00133 Rome, Italy.
³ Respiratory Disease and Lung Function Unit, Department of Medicine and Surgery, University of Parma, 43126 Parma, Italy.

Abstract

Background: Triple fixed-dose combination (FDC) therapy is recommended in severe chronic obstructive pulmonary disease (COPD) patients experiencing frequent exacerbations and/or symptoms not controlled by dual FDCs. Since no randomized controlled trials (RCTs) have directly compared the different inhaled corticosteroid/long-acting β2-adrenoceptor agonist/long-acting muscarinic antagonist (ICS/LABA/LAMA) FDCs, we performed a meta-analysis to compare the impact of the current available ICS/LABA/LAMA FDCs in COPD. Methods: A meta-analysis was performed by connecting beclomethasone dipropionate/formoterol fumarate/glycopyrronium bromide or glycopyrrolate (BDP/FOR/GLY), budesonide (BUD)/GLY/FOR, and fluticasone furoate/umeclidinium bromide/vilanterol (FF/UMEC/VI) FDCs via ICS/LABA or LABA/LAMA FDCs arms. The safety and efficacy profiles were investigated, and the Implemented Bidimensional Surface under the cumulative ranking curve analysis (IBiS) was carried out. Protocol registration: CRD42022301189. Results: Data from 21,809 COPD patients were extracted from the ETHOS, IMPACT, KRONOS, and TRILOGY studies. No significant (p > 0.05) differences were detected across the triple FDCs with respect to the risk of exacerbation, trough forced expiratory volume in the first second (FEV1), transition dyspnea index (TDI), St. George’s Respiratory Questionnaire (SGRQ), risk of serious adverse events (SAEs), cardiovascular (CV) SAEs, pneumonia, and all-cause mortality. According to IBiS score, BDP/FOR/GLY 200/12/25 µg twice daily (BID) was the FDC reporting the best combined efficacy/safety profile (area 41.41%), although FF/UMEC/VI 100/62.5/25 µg once daily (QD) showed the greatest efficacy profile (50.54%). The protection against mortality related to the dose of ICS. Conclusions: All triple FDCs are effective and safe in COPD regardless of the regimen of administration (twice daily vs. once daily), with no relevant difference in the risk of CV SAEs and pneumonia.

Keywords: COPD; efficacy; indirect comparison; network meta-analysis; rank; safety; triple FDCs.

Grants and funding

This research received no external funding.