title: Safety Considerations with Dual Bronchodilator Therapy in COPD: An Update.
abstract: Combining a long-acting β2-agonist (LABA) with a long-acting anti-muscarinic agent (LAMA) provides synergistic benefit on airway smooth muscle relaxation, which may have major implications for the use of LABA/LAMA combinations in the treatment of chronic obstructive pulmonary disease (COPD). There are four different approved LAMA/LABA fixed-dose combinations (FDCs)-glycopyrronium/indacaterol, umeclidinium/vilanterol, tiotropium/olodaterol, and aclidinium/formoterol-and another, glycopyrronium/formoterol, that is still under clinical development. Many pivotal trials have shown that all of these FDCs are more effective than monotherapies in inducing bronchodilation and do not amplify the possible adverse events (AEs) that are characteristic of LAMAs and LABAs when used as monotherapy. Unfortunately, these clinical trials have included a very small and highly selected fraction of the COPD patient population. Therefore, it is questionable whether such data can be extrapolated to a larger, 'real-life' population of patients with COPD, especially given that COPD patients with co-morbidities are often excluded from clinical trials, COPD is a major risk factor for most cardiovascular diseases, and both LAMAs and LABAs have a high potential to impact cardiac activities. All clinical trials have been conducted under widely varying conditions and, consequently, AE rates of a drug observed in a clinical trial cannot be directly compared with rates in the clinical trials of another drug and may not reflect the rates observed in practice. Head-to-head studies comparing the different LAMA/LABA FDCs that will include the true patients that we meet in our everyday practice are absolutely essential if we wish to make a therapeutic choice that is not purely empirical.
authors.affiliation: Department of Experimental Medicine, Second University of Naples, Naples, Italy.
authors.forename: Maria Gabriella
authors.initials: MG
authors.lastname: Matera
authors.affiliation: Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Rogliani
authors.affiliation: Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy.
authors.forename: Luigino
authors.initials: L
authors.lastname: Calzetta
authors.affiliation: Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy. mario.cazzola@uniroma2.it.
authors.forename: Mario
authors.initials: M
authors.lastname: Cazzola
mesh_terms: D058666:Adrenergic beta-2 Receptor Agonists / Q000008:administration & dosage / Q000627:therapeutic use*; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D004338:Drug Combinations; D006801:Humans; D018727:Muscarinic Antagonists / Q000008:administration & dosage / Q000627:therapeutic use*; D000071066:Patient Reported Outcome Measures; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy*; D018570:Risk Assessment; D016896:Treatment Outcome
chemical_list: D058666:Adrenergic beta-2 Receptor Agonists; D001993:Bronchodilator Agents; D004338:Drug Combinations; D018727:Muscarinic Antagonists