Effectiveness and Safety of COPD Maintenance Therapy with Tiotropium/Olodaterol versus LABA/ICS in a US Claims Database

Jennifer K Quint, Jukka Montonen, Daina B Esposito, Xintong He, Leslie Koerner, Laura Wallace, Alberto de la Hoz, Marc Miravitlles, Jennifer K Quint, Jukka Montonen, Daina B Esposito, Xintong He, Leslie Koerner, Laura Wallace, Alberto de la Hoz, Marc Miravitlles

Abstract

Introduction: In patients with chronic obstructive pulmonary disease (COPD), treatment with long-acting muscarinic antagonist (LAMA)/long-acting β2-agonist (LABA) combination therapy significantly improves lung function versus LABA/inhaled corticosteroid (ICS). To investigate whether LAMA/LABA could provide better clinical outcomes than LABA/ICS, this non-interventional database study assessed the risk of COPD exacerbations, pneumonia, and escalation to triple therapy in patients with COPD initiating maintenance therapy with tiotropium/olodaterol versus any LABA/ICS combination.

Methods: Administrative healthcare claims and laboratory results data from the US HealthCore Integrated Research Databasesm were evaluated for patients with COPD initiating tiotropium/olodaterol versus LABA/ICS treatment (January 2013-March 2019). Patients were aged at least 40 years with a diagnosis of COPD (but not asthma) at cohort entry. A Cox proportional hazard regression model was used (as-treated analysis) to assess risk of COPD exacerbation, community-acquired pneumonia, and escalation to triple therapy, both individually and as a combined risk of any one of these events. Potential imbalance of confounding factors between cohorts was handled using fine stratification, reweighting, and trimming by exposure propensity score (high-dimensional); subgroup analyses were conducted on the basis of blood eosinophil levels and exacerbation history.

Results: The total population consisted of 61,985 patients (tiotropium/olodaterol n = 2684; LABA/ICS n = 59,301); after reweighting, the total was 42,953 patients (tiotropium/olodaterol n = 2600; LABA/ICS n = 40,353; mean age 65 years; female 54.5%). Patients treated with tiotropium/olodaterol versus LABA/ICS experienced a reduction in the risk of COPD exacerbations (adjusted hazard ratio 0.76 [95% confidence interval 0.68, 0.85]), pneumonia (0.74 [0.57, 0.97]), escalation to triple therapy (0.22 [0.19, 0.26]), and any one of these events (0.45 [0.41, 0.49]); the combined risk was similar irrespective of baseline eosinophils and exacerbation history.

Conclusions: In patients with COPD, tiotropium/olodaterol was associated with a lower risk of COPD exacerbations, pneumonia, and escalation to triple therapy versus LABA/ICS, both individually and in combination; the combined risk was reduced irrespective of baseline eosinophils or exacerbation history.

Trial registration: ClinicalTrials.gov identifier, NCT04138758 (registered 23 October 2019).

Keywords: Chronic obstructive pulmonary disease; Corticosteroids; Database; Olodaterol; Tiotropium.

Figures

Fig. 1
Fig. 1
Formation of the study cohort. Percentage values show the proportion of individuals lost from the study cohort at each step compared with those with at least one COPD diagnosis (n = 237,328 [100%]). COPD chronic obstructive pulmonary disease, ICS inhaled corticosteroids, LABA long-acting β2-agonist, LAMA long-acting muscarinic antagonist, Olo olodaterol, Tio tiotropium
Fig. 2
Fig. 2
Risk of exacerbation, pneumonia, escalation to triple therapy, or a combination of these events (exacerbation, or pneumonia, or escalation to triple therapy) in patients receiving tiotropium/olodaterol versus LABA/ICS. Hazard ratios were derived using Cox proportional hazard models. The Cox proportional hazard model was further adjusted for patient characteristics found to be imbalanced after application of the propensity score, where imbalance was defined as standardized differences greater than 10%. aHR adjusted hazard ratio, CI confidence interval, COPD chronic obstructive pulmonary disease, ICS inhaled corticosteroids, LABA long-acting β2-agonist, Olo olodaterol, Tio tiotropium
Fig. 3
Fig. 3
Subgroup analyses for the risk of exacerbations in patients receiving tiotropium/olodaterol versus LABA/ICS. Hazard ratios were derived using Cox proportional hazard models. The Cox proportional hazard model was further adjusted for patient characteristics found to be imbalanced after application of the propensity score, where imbalance was defined as standardized differences greater than 10%. aHR adjusted hazard ratio, CI confidence interval, ICS inhaled corticosteroids, LABA long-acting β2-agonist, Olo olodaterol, Tio tiotropium
Fig. 4
Fig. 4
Subgroup analyses for the risk of exacerbation or pneumonia or escalation to triple therapy in patients receiving tiotropium/olodaterol versus LABA/ICS. Hazard ratios were derived using Cox proportional hazard models. The Cox proportional hazard model was further adjusted for patient characteristics found to be imbalanced after application of the propensity score, where imbalance was defined as standardized differences greater than 10%. aHR adjusted hazard ratio, CI confidence interval, ICS inhaled corticosteroids, LABA long-acting β2-agonist, Olo olodaterol, Tio tiotropium

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