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Safety Considerations with Dual Bronchodilator Therapy in COPD: An Update

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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.

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Authors and Affiliations

  1. Department of Experimental Medicine, Second University of Naples, Naples, Italy

    Maria Gabriella Matera

  2. Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy

    Paola Rogliani, Luigino Calzetta & Mario Cazzola

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  1. Maria Gabriella Matera
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  2. Paola Rogliani
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  3. Luigino Calzetta
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  4. Mario Cazzola
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Correspondence to Mario Cazzola.

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No sources of funding were used to assist in the preparation of this study.

Conflicts of interest

Maria Gabriella Matera has undertaken research funded by Novartis, is a member of the Boehringer Ingelheim speaker bureau, and has participated as a speaker in scientific meetings and courses under the sponsorship of Almirall, AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, and Novartis. Paola Rogliani has participated as a speaker and advisor in scientific meetings and courses under the sponsorship of Almirall, AstraZeneca, Biofutura, Boehringer Ingelheim, GlaxoSmithKline, Menarini Group, and Novartis and is a member of the AstraZeneca and Boehringer Ingelheim speaker bureau. Luigino Calzetta has undertaken research funded by Novartis. Mario Cazzola is a consultant at Chiesi Farmaceutici, Zambon, and Novartis; has undertaken research funded by Novartis, AstraZeneca, and Almirall; is a member of the Novartis, GSK, AstraZeneca, Zambon, Mundipharma, and Boehringer Ingelheim speaker bureaus; and has participated as a speaker and advisor in scientific meetings and courses under the sponsorship of Almirall, AstraZeneca, Biofutura, Boehringer Ingelheim, GlaxoSmithKline, Menarini Group, and Novartis. Luigino Calzetta has no conflicts of interest. The Department of Systems Medicine of the University of Rome Tor Vergata was funded by Almirall, Boehringer Ingelheim, and Novartis to conduct research in the respiratory field.

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Matera, M.G., Rogliani, P., Calzetta, L. et al. Safety Considerations with Dual Bronchodilator Therapy in COPD: An Update. Drug Saf 39, 501–508 (2016). https://doi.org/10.1007/s40264-016-0402-4

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