Background Patients with chronic obstructive pulmonary disease (COPD) have few options for treatment. The effi cacy and safety of the phosphodiesterase-4 inhibitor rofl umilast have been investigated in studies of patients with moderate-to-severe COPD, but not in those concomitantly treated with longacting inhaled bronchodilators. The eff ect of rofl umilast on lung function in patients with COPD that is moderate to severe who are already being treated with salmeterol or tiotropium was investigated. Methods 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 rofl umilast 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 (FEV1). Analysis was by intention to treat. The studies are registered with ClinicalTrials.gov, number NCT00313209 for M2-127, and NCT00424268 for M2-128. Findings In the salmeterol plus rofl umilast trial, 466 patients were assigned to and treated with rofl umilast and 467 with placebo; in the tiotropium plus rofl umilast trial, 371 patients were assigned to and treated with rofl umilast and 372 with placebo. Compared with placebo, rofl umilast consistently improved mean prebronchodilator FEV1 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 FEV1 was noted in both groups. Furthermore, rofl umilast had benefi cial eff ects 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 rofl umilast groups. These adverse events were associated with increased patient withdrawal. Interpretation Rofl umilast improves lung function in patients with COPD treated with salmeterol or tiotropium, and could become an important treatment for these patients.
ROFLOMILAST IN MODERATE-TO-SEVERE CHRONIC OBSTRUCTIVE PULMONARY DISEASE TREATED WITH LONGACTING BRONCHODILATORS: TWO RANDOMISED CLINICAL TRIALS
PAGGIARO, PIER LUIGI
2009-01-01
Abstract
Background Patients with chronic obstructive pulmonary disease (COPD) have few options for treatment. The effi cacy and safety of the phosphodiesterase-4 inhibitor rofl umilast have been investigated in studies of patients with moderate-to-severe COPD, but not in those concomitantly treated with longacting inhaled bronchodilators. The eff ect of rofl umilast on lung function in patients with COPD that is moderate to severe who are already being treated with salmeterol or tiotropium was investigated. Methods 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 rofl umilast 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 (FEV1). Analysis was by intention to treat. The studies are registered with ClinicalTrials.gov, number NCT00313209 for M2-127, and NCT00424268 for M2-128. Findings In the salmeterol plus rofl umilast trial, 466 patients were assigned to and treated with rofl umilast and 467 with placebo; in the tiotropium plus rofl umilast trial, 371 patients were assigned to and treated with rofl umilast and 372 with placebo. Compared with placebo, rofl umilast consistently improved mean prebronchodilator FEV1 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 FEV1 was noted in both groups. Furthermore, rofl umilast had benefi cial eff ects 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 rofl umilast groups. These adverse events were associated with increased patient withdrawal. Interpretation Rofl umilast improves lung function in patients with COPD treated with salmeterol or tiotropium, and could become an important treatment for these patients.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
