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| |  Roflumilast Reduces Exacerbation Risk, Improves Lung Function in Patients With COPD: Presented at ERS By Evelyn Harvey VIENNA, Austria -- September 15, 2009 -- The phosphodiesterase-4 inhibitor roflumilast can significantly improve lung function and prevent both moderate and severe exacerbations in patients with chronic obstructive pulmonary disease (COPD), according to results from replicate studies presented here at the 19th Annual Congress of the European Respiratory Society (ERS). The results were presented and discussed on September 13 by Peter Calverly, MD, School of Clinical Sciences, University of Liverpool, Liverpool, United Kingdom, and on September 14 by Fernando Martinez, MD, Department of Internal Medicine, University of Michigan Health System, Ann Arbor, Michigan. The double-blind, multicentre AURA and HERMES trials both compared oral daily roflumilast 500 mg (n = 1,537) to placebo (n = 1,554) for 1 year and were identical in design. Inclusion criteria for the trials were as follows: age 40 or older, clinically diagnosed COPD with postbronchodilator forced expiratory volume in 1 second (FEV1) of 50% or less of predicted value. Individuals with significant comorbidities were excluded. Patients were stratified according to smoking status and concomitant treatment with long-acting beta2 agonists or anticholinergics. Baseline characteristics were similar in the roflumilast and placebo groups across both trials. The use of inhaled corticosteroids (ICS) was not permitted during the trial; however, approximately 40% of subjects in each group were pretreated with ICS. A pooled analysis demonstrated that roflumilast increased prebronchodilator FEV1 by 48 mL compared with placebo (P < .0001). Significant improvements in postbronchodilator FEV1 were also observed. The rate of total exacerbations did not differ significantly, but moderate and/or severe exacerbations were reduced by 16.9% in the roflumilast groups compared to placebo (P < .0003). Patients’ perception of dyspnoea also improved in the roflumilast groups. The incidence of adverse events (AEs) was higher in the roflumilast treatment arms than in placebo groups, with 14.2% and 11.5% of respective patients discontinuing due to AEs. COPD and gastrointestinal AEs were the most frequently reported. No effects on the cardiovascular or central nervous systems were reported, nor were there any mortalities observed. A surprisingly consistent weight loss of 2.17 kg on average was observed in the roflumilast subjects, but not in the placebo group (P < .0001). This was only partially attributable to increased gastrointestinal AEs in the roflumilast groups. “The weight loss was most pronounced in subjects with a [body mass index] over 30,” commented Dr. Martinez. “In these cases, it may not even be considered an adverse event. Weight was regained after roflumilast treatment stopped.” The withdrawal of COPD patients from ICS was a potential confounding factor in the trial; however, the proportions of pretreated patients were similar between groups. The differential rate of dropout between the roflumilast and placebo groups was also noted. A biphasic dropout rate was, in fact, apparent, with a higher proportion of roflumilast subjects leaving the study within the first 12 weeks due to AEs, whereas placebo patients withdrew toward the end because of poorly controlled COPD. “Roflumilast could have a role in COPD therapy in addition to bronchodilators,” Professor Calverly concluded. The existence of distinct subgroups of COPD patients raises the possibility that roflumilast is suitable as a future targeted therapy, subject to further trials. Funding for these studies was provided by Nycomed. [Presentation title: Roflumilast Treatment Over One Year and as an Add on Therapy in COPD]
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