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Observational Study
. 2016 Nov;56(11):1423-1432.
doi: 10.1002/jcph.750.

Role of Tiotropium in Reducing Exacerbations of Chronic Obstructive Pulmonary Disease When Combined With Long-Acting β2 -Agonists and Inhaled Corticosteroids: The OUTPUL Study

Eliana Ferroni  1 , Valeria Belleudi  1 , Silvia Cascini  1 , Mirko Di Martino  1 , Ursula Kirchmayer  1 , Riccardo Pistelli  2 , Elisabetta Patorno  3 , Giulio Formoso  4 , Danilo Fusco  1 , Carlo A Perucci  5 , Marina Davoli  1 , Nera Agabiti  6 ; OUTPUL Study Group  1
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Observational Study

Role of Tiotropium in Reducing Exacerbations of Chronic Obstructive Pulmonary Disease When Combined With Long-Acting β2 -Agonists and Inhaled Corticosteroids: The OUTPUL Study

Eliana Ferroni et al. J Clin Pharmacol. 2016 Nov.

Abstract

Combined inhaled therapy in chronic obstructive pulmonary disease (COPD) is commonly used, but its benefits remain controversial. We assessed the effect of tiotropium in reducing COPD exacerbations when combined with long-acting β2 agonists (LABA) and/or inhaled corticosteroids (ICS). This new-user cohort study is based on administrative data from 3 Italian regions. We identified adults hospitalized for COPD from 2006 to 2009 who were newly prescribed a fixed LABA/ICS combination (double therapy). We classified patients according to whether tiotropium was also prescribed (triple therapy), using both intention-to-treat and as-treated approaches, and followed them for 1 year. COPD exacerbations were measured as outcomes. Multivariate and propensity score-adjusted hazard ratios (HRs, 95%CI) were calculated with Cox regression models. We identified 5717 new users of LABA/ICS of which 31.9% initiated triple therapy. In the intention-to-treat analysis, the multivariate adjusted HR for moderate, severe, and any exacerbations were 1.02 (95%CI 0.89-1.16), 0.92 (95%CI 0.76-1.12), and 1.08 (95%CI 0.91-1.28), respectively. The propensity score adjustment produced similar results. In the subcohort of patients with previous exacerbations, triple therapy was significantly associated with reduced risk of moderate exacerbations, compared to double therapy (HR 0.68, 95%CI 0.48-0.98 in intention-to-treat approach). In conclusion, the addition of tiotropium to LABA/ICS did not reduce COPD exacerbations compared to LABA/ICS alone. A protective role for moderate exacerbations was found in patients at risk of frequent exacerbations. Given the impact of exacerbations on health status and prognosis, it is crucial to target COPD patients for optimal treatment.

Keywords: chronic obstructive pulmonary disease; comparative effectiveness; exacerbation; inhaled therapy; tiotropium.

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Figures

Figure 1
Figure 1
Study designs: (1) intention‐to‐treat and (2) as‐treated approaches. LABA, Long acting beta 2 agonists; ICS, Inhaled corticosteroids.
Figure 2
Figure 2
Predictive model for any exacerbation calculated with the intention‐to‐treat approach.
See this image and copyright information in PMC

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