Journal Article

Roflumilast in moderate-to-severe chronic obstructive pulmonary disease treated with longacting bronchodilators: two randomised clinical trials

Martinez, Fernando J, Calverley, Peter MA, Izquierdo-Alonso, José Luis, Brose, Manja, Fabbri, Leonardo M, Bundschuh, Daniela S, Rabe, Klaus F

2009

Overview

Patients with chronic obstructive pulmonary disease (COPD) have few options for treatment. The efficacy and safety of the phosphodiesterase-4 inhibitor roflumilast have been investigated in studies of patients with moderate-to-severe COPD, but not in those concomitantly treated with longacting inhaled bronchodilators. The effect of roflumilast on lung function in patients with COPD that is moderate to severe who are already being treated with salmeterol or tiotropium was investigated. In two double-blind, multicentre studies done in an outpatient setting, after a 4-week run-in, patients older than 40 years with moderate-to-severe COPD were randomly assigned to oral roflumilast 500 μg or placebo once a day for 24 weeks, in addition to salmeterol (M2-127 study) or tiotropium (M2-128 study). The primary endpoint was change in prebronchodilator forced expiratory volume in 1 s (FEV 1). Analysis was by intention to treat. The studies are registered with ClinicalTrials.gov, number NCT00313209 for M2-127, and NCT00424268 for M2-128. In the salmeterol plus roflumilast trial, 466 patients were assigned to and treated with roflumilast and 467 with placebo; in the tiotropium plus roflumilast trial, 371 patients were assigned to and treated with roflumilast and 372 with placebo. Compared with placebo, roflumilast consistently improved mean prebronchodilator FEV 1 by 49 mL (p<0·0001) in patients treated with salmeterol, and 80 mL (p<0·0001) in those treated with tiotropium. Similar improvement in postbronchodilator FEV 1 was noted in both groups. Furthermore, roflumilast had beneficial effects on other lung function measurements and on selected patient-reported outcomes in both groups. Nausea, diarrhoea, weight loss, and, to a lesser extent, headache were more frequent in patients in the roflumilast groups. These adverse events were associated with increased patient withdrawal. Roflumilast improves lung function in patients with COPD treated with salmeterol or tiotropium, and could become an important treatment for these patients. Nycomed.

• Publisher: Elsevier Ltd,Elsevier,Elsevier Limited
• Subject: Administration, Inhalation / Administration, Oral / Aged / Albuterol - analogs & derivatives / Albuterol - therapeutic use / Aminopyridines - therapeutic use / Analysis of Variance / Benzamides - therapeutic use / Biological and medical sciences / Bronchodilator Agents - therapeutic use / Bronchodilators / Chronic obstructive pulmonary disease / Clinical medicine / Clinical trials / Cyclopropanes - therapeutic use / Diarrhea / Double-Blind Method / Drug therapy / Drug Therapy, Combination / Female / Forced Expiratory Volume - drug effects / General aspects / Headache / Humans / Internal Medicine / Lung / Male / Medical sciences / Medical treatment / Middle Aged / Molecular structure / Motivation / Nausea / Phosphodiesterase 4 Inhibitors / Phosphodiesterase Inhibitors - therapeutic use / Pulmonary Disease, Chronic Obstructive - diagnosis / Pulmonary Disease, Chronic Obstructive - drug therapy / Pulmonary Disease, Chronic Obstructive - etiology / Regression Analysis / Respiratory function / salmeterol / Salmeterol Xinafoate / Scopolamine Derivatives - therapeutic use / Severity of Illness Index / Side effects / Smoking - epidemiology / Smoking cessation / Studies / Tiotropium Bromide / Treatment Outcome / Vital Capacity - drug effects