The Effect on Total Mortality of Adding Inhaled Corticosteroids to Long-Acting Bronchodilators for COPD: A Real Practice Analysis in Italy

Abstract

Purpose. Chronic therapy with long-acting bronchodilators (LB) is recommended to treat moderate-to-severe COPD. Although the benefits of adding inhaled corticosteroid (ICS) to LB are still unclear, patients who experience repeated exacerbations are suggested to add ICS to their LB treatment. The objective of this study is to analyze whether adding ICS to LB therapy reduces mortality. Methods. We identified a cohort of patients discharged from hospital with COPD diagnosis between 2006 and 2009. The first prescription for LB or ICS following discharge was defined as the index prescription. Only new users were included (no use of any study drug in the 6 months before treatment). A 4-day time window was used to classify patients into “LB alone” or “LB plus ICS” initiators. We used propensity score to balance the study groups. Sensitivity analyses were performed in patients with recent out-of-hospital exacerbations. Results. Among the 18615 adults enrolled, 12207 initiated “LB plus ICS” therapy and 6408 “LB alone.” Crude mortality rates were 110 and 143 cases per 1000 person-years in the “LB plus ICS” and “LB alone” groups, respectively. The adjusted hazard ratio (HR) was 0.83 (95% CI: 0.72–0.97; p-value: 0.024). When analyzing patients with recent out-of-hospital exacerbations, the benefit of the combination therapy was more pronounced, HR = 0.63 (95% CI: 0.44–0.90; p-value: 0.012). Discussion. Our findings showed a beneficial effect on mortality of adding inhaled corticosteroids to long-acting bronchodilators. The advantage was much more pronounced in patients with frequent exacerbations.

Keywords:

• chronic obstructive pulmonary disease
• inhaled corticosteroid
• long-acting bronchodilators
• repeated exacerbations
• total mortality

Acknowledgments

The authors thank Professor Sebastian Schneeweiss in the Division of Pharmacoepidemiology, Brigham and Women's Hospital, Boston, for the precious advice and helpful discussions.

Funding

This work was partially funded by the Italian Agency of Medicines; research project code: FARM8ZBT93.

Declaration of interest statement

The authors declare that they have no conflicts of interest.

Mirko Di Martino contributed to the concept and design of the study, the analysis of data, the interpretation of results, and the writing of the article.

Silvia Cascini, Ursula Kirchmayer, Luigi Pinnarelli, Elisabetta Patorno and Danilo Fusco contributed to the design of the study, the interpretation of results, and the writing of the article.

Valeria Belleudi, Lisa Bauleo and Claudio Voci contributed to the design of the study, the acquisition of data from the health information systems, the statistical analysis, the interpretation of results, and the writing of the article.

Nera Agabiti, Riccardo Pistelli and Marina Davoli contributed to the concept of the study, the interpretation of results, the writing of the article, and the critical revision of the paper for important intellectual content, and they have given their final approval of the version submitted for publication.

All authors agree to be accountable for all aspects of the work and ensure that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

The OUTPUL study group

Nera Agabiti (1), Mirko Di Martino (1), Ursula Kirchmayer (1), Lisa Bauleo (1), Silvia Cascini (1), Valeria Belleudi (1), Luigi Pinnarelli (1), Danilo Fusco (1), Marina Davoli (1), Carlo A Perucci (2), Nicola Magrini (3), Giulio Formoso (3), Anna Maria Marata (3), Riccardo Pistelli (4), Vittoria Colamesta (4), Carlo Zocchetti (5), Claudio Voci (6).

1. 1. Department of Epidemiology, Lazio Regional Health Service, Roma, Italy.

2. 2. Senior Epidemiologist Consultant, Roma, Italy.

3. 3. Emilia-Romagna Regional Health and Social Care Agency, Bologna, Italy.

4. 4. Department of Respiratory Physiology, Catholic University, Roma, Italy.

5. 5. Regional Health Authority, Lombardia Region, Milano, Italy.

6. 6. Management Control Unit, Modena University Hospital, Modena, Italy.