Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Observational Study
. 2024 Aug 21:19:1879-1892.
doi: 10.2147/COPD.S465517. eCollection 2024.

Long-Term Safety of Roflumilast in Patients with Chronic Obstructive Pulmonary Disease, a Multinational Observational Database Cohort Study

Edeltraut Garbe  1 , Fabian Hoti  2 , Tania Schink  1 , Kristian Svendsen  3 , Haydar Al-Eid  4 , Per Arkhammar  5 , Marie Carlholm  6 , Harald Fjällbrant  6 , Stefan Franzén  7   8 , Cecilia Hedlund  9 , Bianca Kollhorst  10 , Atul Kumar  11 , Muriel Lobier  2 , Vasili Mushnikov  2 , Tore Persson  9 , Xu Qiao  2 , Aaro Salosensaari  12 , Wiebke Schäfer  1 , Nicholas M Sicignano  13 , Gunnar Johansson  14 , Eileen O Dareng  15
Affiliations
Observational Study

Long-Term Safety of Roflumilast in Patients with Chronic Obstructive Pulmonary Disease, a Multinational Observational Database Cohort Study

Edeltraut Garbe et al. Int J Chron Obstruct Pulmon Dis. .

Abstract

Purpose: This study evaluated the long-term safety of roflumilast in patients with chronic obstructive pulmonary disease or chronic bronchitis using electronic healthcare databases from Germany, Norway, Sweden, and the United States (US).

Patients and methods: The study population consisted of patients aged ≥40 years who had been exposed to roflumilast and a matched cohort unexposed to roflumilast. The matching was based on sex, age, calendar year of cohort entry date (2010-2011, 2012, or 2013), and a propensity score that included variables such as demographics, markers of chronic obstructive pulmonary disease (COPD) severity and morbidity, and comorbidities. In comparison to the unexposed matched cohort (never use), three exposure definitions were used for the exposed matched cohort: ever use, use status (current, recent, past use), and cumulative duration of use. The main outcome was 5-year all-cause mortality. Cox regression models were used to estimate crude and adjusted hazard ratios (HRs) and 95% confidence intervals (CI).

Results: 112,541 unexposed and 23,239 exposed patients across countries were included. Some variables remained unbalanced after matching, indicating higher COPD disease severity among the exposed patients. Adjusted HRs of 5-year all-cause mortality for "ever use" of roflumilast, compared to "never use", were 1.12 (95% CI, 1.08-1.17) in Germany, 1.00 (95% CI, 0.92-1.08) in Norway, 0.98 (95% CI, 0.92-1.04) in Sweden, and 1.16 (95% CI, 1.12-1.20) in the US. Compared to never users, there was a decrease in 5-year mortality risk observed among "current users" in Germany (HR: 0.93, 95% CI: 0.88-0.98), Norway (HR: 0.77, 95% CI: 0.67-0.87), and Sweden (HR: 0.80, 95% CI: 0.73-0.88).

Conclusion: There was no observed increase in 5-year mortality risk with the use of roflumilast in Sweden or Norway. A small increase in 5-year mortality risk was observed in Germany and the US in the ever versus never comparison, likely due to residual confounding by indication.

Keywords: 5-year all-cause mortality; COPD; electronic healthcare database; propensity score; roflumilast.

PubMed Disclaimer

Conflict of interest statement

Edeltraut Garbe has been chairwoman of the Department of Clinical Epidemiology at the Leibniz Institute for Prevention Research and Epidemiology – BIPS and in this function occasionally performed studies for pharmaceutical industries. The pharmaceutical companies included Byk-Gulden, Nycomed, Bayer, Celgene, GlaxoSmithKline, Mundipharma, Novartis, Sanofi-Aventis, Sanofi Pasteur MSD, and STADA. She has been a consultant to Bayer-Schering, Nycomed, GlaxoSmithKline, Schwabe, Teva, and Novartis, as well as to AstraZeneca (including this study). Per Arkhammar, Marie Carlholm, Eileen O Dareng, Harald Fjällbrant, and Stefan Franzén are employees and shareholders of AstraZeneca. Atul Kumar is an employee of AstraZeneca. Tore Persson is an AstraZeneca contractor and shareholder. Cecilia Hedlund is an AstraZeneca contractor. Gunnar Johansson has served on advisory boards arranged by AstraZeneca, Novartis, and Teva. Bianca Kollhorst, Wiebke Schäfer, and Tania Schink are working at an independent, non-profit research institute, the Leibniz Institute for Prevention Research and Epidemiology – BIPS. Unrelated to this study, BIPS occasionally conducts studies financed by the pharmaceutical industry. These are post-authorization safety studies (PASS) requested by health authorities and performed in line with the ENCePP Code of Conduct. Fabian Hoti, Muriel Lobier, Aaro Salosensaari, Xu Qiao, and Vasili Mushnikov are employed by IQVIA, a contract research organization that conducts studies financed by the pharmaceutical industry. Nicholas Sicignano and Kristian Svendsen confirm that there are no known conflicts of interest associated with this publication and there has been no significant financial support for this work that could have influenced its outcome. The authors report no other conflicts of interest in this work.

References

    1. Soriano JB. Prevalence and attributable health burden of chronic respiratory diseases, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet Respir Med. 2020;8(6):585–596. doi:10.1016/s2213-2600(20)30105-3 - DOI - PMC - PubMed
    1. Safiri S, Carson-Chahhoud K, Noori M, et al. Burden of chronic obstructive pulmonary disease and its attributable risk factors in 204 countries and territories, 1990-2019: results from the Global Burden of Disease Study 2019. BMJ. 378:e069679. doi:10.1136/bmj-2021-069679 - DOI - PMC - PubMed
    1. Park SC, Kim DW, Park EC, et al. Mortality of patients with chronic obstructive pulmonary disease: a nationwide populationbased cohort study. Korean J Intern Med. 2019;34(6):1272–1278. doi:10.3904/kjim.2017.428 - DOI - PMC - PubMed
    1. Mathers CD, Loncar D. Projections of global mortality and burden of disease from 2002 to 2030. PLoS Med. 2006;3(11):e442. doi:10.1371/journal.pmed.0030442 - DOI - PMC - PubMed
    1. Mejza F, Gnatiuc L, Buist AS, et al. Prevalence and burden of chronic bronchitis symptoms: results from the BOLD study. Eur Respir J. 2017;50(5). doi:10.1183/13993003.00621-2017 - DOI - PMC - PubMed

Publication types

MeSH terms