Journal Article

Roflumilast—an oral anti-inflammatory treatment for chronic obstructive pulmonary disease: a randomised controlled trial

Bredenbröker, Dirk, Witte, Stephan, Bateman, Eric D, Rabe, Klaus F, Bethke, Thomas D, O'Donnell, Denis

2005

Overview

Chronic obstructive pulmonary disease (COPD) is characterised by progressive airflow limitation associated with chronic inflammation. There are few treatment options for the disease. This study assessed the efficacy and safety of roflumilast, a phosphodiesterase-4 inhibitor, in patients with moderate to severe COPD. This phase III, multicentre, double-blind, randomised, placebo-controlled study was undertaken in an outpatient setting. 1411 patients with COPD were randomly assigned roflumilast 250 μg (n=576), roflumilast 500 μg (n=555), or placebo (n=280) given orally once daily for 24 weeks. Primary outcomes were postbronchodilator FEV 1 and health-related quality of life. Secondary outcomes included other lung function parameters and COPD exacerbations. Analyses were by intention to treat. 1157 (82%) patients completed the study; 32 (11%) withdrew from the placebo group, 100 (17%) from the roflumilast 250 μg group, and 124 (22%) from the roflumilast 500 μg group. Postbronchodilator FEV 1 at the end of treatment significantly improved with roflumilast 250 μg (by 74 mL [SD 18]) and roflumilast 500 μg (by 97 mL [18]) compared with placebo (p<0·0001). Improvement in health-related quality of life was greater with roflumilast 250 μg (−3·4 units [0·6]) and roflumilast 500 μg (−3·5 units [0·6]) than with placebo (−1·8 units [0·8]), although the differences between treatment groups were not significant. The mean numbers of exacerbations per patient were 1·13 (2·37), 1·03 (2·33), and 0·75 (1·89) with placebo, roflumilast 250 μg, and roflumilast 500 μg, respectively. Most adverse events were mild to moderate in intensity and resolved during the study. Roflumilast is a promising candidate for anti-inflammatory COPD treatment because it improved lung function and reduced exacerbations compared with placebo. Long-term studies are needed to fully assess the effect on health-related quality of life.

• Publisher: Elsevier Ltd,Lancet,Elsevier Limited
• Subject: Administration, Oral / Adult / Aged / Aged, 80 and over / Aminopyridines - administration & dosage / Anti-Inflammatory Agents - administration & dosage / Benzamides - administration & dosage / Biological and medical sciences / Chronic obstructive pulmonary disease / Chronic obstructive pulmonary disease, asthma / Clinical outcomes / Clinical trials / Cyclopropanes - administration & dosage / Disease / Female / Forced Expiratory Volume / General aspects / Humans / Lungs / Male / Maximal Midexpiratory Flow Rate / Medical sciences / Medical treatment / Middle Aged / Phosphodiesterase Inhibitors - administration & dosage / Pneumology / Pulmonary Disease, Chronic Obstructive - drug therapy / Pulmonary Disease, Chronic Obstructive - physiopathology / Quality of Life / Respiratory function / Vital Capacity