Journal Article

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

Franzén, Stefan, Kollhorst, Bianca, Schink, Tania, Svendsen, Kristian, Johansson, Gunnar, Sicignano, Nicholas, Arkhammar, Per, Hedlund, Cecilia, Fjällbrant, Harald, Al-Eid, Haydar, Schäfer, Wiebke, Hoti, Fabian, Qiao, Xu, Dareng, Eileen, Mushnikov, Vasili, Persson, Tore, Kumar, Atul, Salosensaari, Aaro, Garbe, Edeltraut, Carlholm, Marie, Lobier, Muriel

2024

Overview

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). 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). 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). 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.

• Publisher: Dove Medical Press Limited,Dove Medical Press Ltd,Dove Press,Dove,Dove Medical Press
• Subject: 5-year all-cause mortality / Adult / Aged / Aged, 80 and over / Agonists / Ambulatory care / Aminopyridines - adverse effects / Aminopyridines - therapeutic use / Benzamides - adverse effects / Benzamides - therapeutic use / Bronchitis / Bronchitis, Chronic - drug therapy / Bronchitis, Chronic - epidemiology / Bronchitis, Chronic - mortality / Chronic obstructive pulmonary disease / Clinical trials / Cohort analysis / Comorbidity / COPD / Cyclopropanes - adverse effects / Cyclopropanes - therapeutic use / Databases, Factual / Diseases / electronic healthcare database / Female / Germany / Humans / Inpatient care / Insurance coverage / Male / Medical research / Medicine, Experimental / Middle Aged / Mortality / Norway / Original Research / Patients / Pharmaceutical industry / Phosphodiesterase 4 Inhibitors - adverse effects / Phosphodiesterase 4 Inhibitors - therapeutic use / propensity score / Pulmonary Disease, Chronic Obstructive - diagnosis / Pulmonary Disease, Chronic Obstructive - drug therapy / Pulmonary Disease, Chronic Obstructive - mortality / Respiratory agents / Risk Assessment / Risk Factors / Roflumilast / Social security / Sweden / Sweden - epidemiology / Time Factors / Treatment Outcome / United Kingdom / United States - epidemiology