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      Current appraisal of single inhaler triple therapy in COPD

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          Abstract

          A single inhaler containing inhaled corticosteroid (ICS)/long-acting beta-agonist (LABA)/long-acting muscarinic antagonist (LAMA) is a more convenient way of delivering triple therapy in patients with COPD. Single triple therapy has been shown to be superior at reducing exacerbations and improving quality of life compared to LABA/LAMA, especially in patients with a prior history of frequent exacerbations and blood eosinophilia, who have ICS responsive disease. The corollary is that patients with infrequent exacerbations who are noneosinophilic may be safely de-escalated from triple therapy to LABA/LAMA without loss of control. Pointedly, there is a substantially increased risk of pneumonia associated with the triple therapy containing fluticasone furoate but not beclometasone dipropionate or budesonide. Since triple therapy is also better than ICS/LABA at reducing exacerbations and improving lung function, symptoms, and quality of life, this brings into question the rationale for using ICS/LABA. Hence, we propose a simplified pragmatic decision process based on symptoms, prior to exacerbation history, and blood eosinophils to select which patients should be given a single triple inhaler or LABA/LAMA. Differences in patient preference of inhaler device, formulations and drugs will also determine which triple inhaler prescribers elect to use.

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          Most cited references 15

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          Triple therapy with budesonide/glycopyrrolate/formoterol fumarate with co-suspension delivery technology versus dual therapies in chronic obstructive pulmonary disease (KRONOS): a double-blind, parallel-group, multicentre, phase 3 randomised controlled trial

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            Eosinophilia, Frequent Exacerbations, and Steroid Response in Chronic Obstructive Pulmonary Disease.

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              Number needed to treat in COPD: exacerbations versus pneumonias.

               Samy Suissa (2013)
              Several recent trials in chronic obstructive pulmonary disease (COPD) have assessed the effectiveness of the fluticasone-salmeterol combination inhaler in preventing COPD exacerbations, while finding an increased risk of pneumonia. The number needed to treat (NNT) is a simple measure to perform the comparative benefit-risk impact, but its calculation involving repeated outcome events such as COPD exacerbations has been incorrect. We describe the proper methods to calculate the NNT and, using data from published trials, apply them to evaluate the relative impact of fluticasone-salmeterol treatment on exacerbations and pneumonias in patients with COPD. We review the fundamental definition of NNT and quantify it for situations with varying follow-up times. We review the 'event-based' NNT, proposed and used for repeated event outcomes, show its inaccuracy, describe its proper use and provide an approximate formula for its application. We show that a 1-year trial of the fluticasone-salmeterol combination versus salmeterol used the incorrect event-based approach to calculate the NNT as two patients that need to be treated for 1 year to prevent one COPD exacerbation, when the proper calculation results in a NNT of 14. In contrast, 20 patients need to be treated to induce one pneumonia case. For the TORCH trial, the NNT is 44 patients treated for 3 years with fluticasone-salmeterol versus salmeterol to prevent one exacerbation compared with 16 patients to induce one pneumonia case. The NNT is a useful measure of the effect of drugs, but its proper calculation is essential to prevent misleading clinical practice guidelines.
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                Author and article information

                Journal
                Int J Chron Obstruct Pulmon Dis
                Int J Chron Obstruct Pulmon Dis
                International Journal of COPD
                International Journal of Chronic Obstructive Pulmonary Disease
                Dove Medical Press
                1176-9106
                1178-2005
                2018
                28 September 2018
                : 13
                : 3003-3009
                Affiliations
                Division of Molecular & Clinical Medicine, Scottish Centre for Respiratory Research, Ninewells Hospital and Medical School, University of Dundee, Scotland, UK, b.j.lipworth@ 123456dundee.ac.uk
                Author notes
                Correspondence: Brian Lipworth, Division of Molecular & Clinical Medicine, Scottish Centre for Respiratory Research, Ninewells Hospital and Medical School, University of Dundee, DD1 9SY, Scotland, UK, Email b.j.lipworth@ 123456dundee.ac.uk
                Article
                copd-13-3003
                10.2147/COPD.S177333
                6167973
                © 2018 Lipworth et al. This work is published and licensed by Dove Medical Press Limited

                The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

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