TY - JOUR
T1 - Treatment of chronic obstructive pulmonary disease with roflumilast, a new phosphodiesterase 4 inhibitor
AU - Gross, Nicholas J.
AU - Giembycz, Mark A.
AU - Rennard, Stephen I.
N1 - Funding Information:
Dr. Nicholas Gross has received honoraria from Nycomed and Forest, the manufacturers of roflumilast. He also received honoraria from Dey LP, AstraZeneca, GlaxoSmithKline, Boehringer-Ingelheim, Pfizer, Novartis, and Almirall. Dr. Mark Giembycz has received honoraria from Nycomed and Forest, the manufacturers of roflumilast. He also received honoraria and/or unrestricted educational grants from AstraZeneca, Gilead Sciences, GlaxoSmithKline, Otsuka, Proctor and Gamble, Sanofi-Aventis, Schering-Plough and the GSK (Canada)/Collaborative Innovation Research Fund. Dr. Stephen Rennard has received honoraria from Nycomed and Forest, the manufacturers of rof-lumilast. He has also received honoraria and grants from American Board of Internal Medicine, American College of Chest Physicians, Almirall, APT Pharma/Britnall, AstraZeneca, American Thoracic Society, Boehringer Ingelheim, California Allergy Society, Chiesi, COPDForum, Creative Educational Concept, France Foundation, Gerson, GlaxoSmithKline, Hoffmann LaRoche, Information TV, Novartis (Horsham), Oriel Therapeutics, Pearl Therapeutics, Pulmatrix, Schering Plough and UBC.
PY - 2010/4
Y1 - 2010/4
N2 - Recent advances in chronic obstructive pulmonary disease (COPD) treatment offer symptom relief, but disease modification remains an unmet goal of pharmacotherapy. Reducing the frequency and severity of COPD exacerbations may help slow disease progression and reduce the morbidity, mortality, and costs associated with these major events. Other desirable characteristics for a COPD treatment include a once-daily dosing schedule, an oral formulation, and a low frequency of systemic side effects. Phosphodiesterase 4 inhibitors have been in clinical development for some years and roflumilast is currently the most advanced of these agents. In this review, the preclinical evidence, clinical safety, and efficacy of roflumilast available in published reports are considered. The data reviewed here suggest that the clinical efficacy of roflumilast occurs through a mechanism unrelated to bronchodilation and may be due to the suppression of lung inflammation. Lung function improved with roflumilast treatment and in some studies, the reduction in exacerbations was substantial and statistically significant. Notably, this effect appeared to be greatest in the subgroup of patients with more severe disease and more severe exacerbations. The evaluation of roflumilast safety largely centers on gastrointestinal adverse events, with diarrhea, nausea, and weight loss occurring more frequently with the drug than placebo. If approved for general use, we expect roflumilast to find its role initially as a substitute for inhaled corticosteroids in the maintenance treatment of severe and very severe disease, particularly in patients who have frequent acute exacerbations, and perhaps as a supplementary drug when symptoms are not adequately controlled by current conventional COPD therapy. ©
AB - Recent advances in chronic obstructive pulmonary disease (COPD) treatment offer symptom relief, but disease modification remains an unmet goal of pharmacotherapy. Reducing the frequency and severity of COPD exacerbations may help slow disease progression and reduce the morbidity, mortality, and costs associated with these major events. Other desirable characteristics for a COPD treatment include a once-daily dosing schedule, an oral formulation, and a low frequency of systemic side effects. Phosphodiesterase 4 inhibitors have been in clinical development for some years and roflumilast is currently the most advanced of these agents. In this review, the preclinical evidence, clinical safety, and efficacy of roflumilast available in published reports are considered. The data reviewed here suggest that the clinical efficacy of roflumilast occurs through a mechanism unrelated to bronchodilation and may be due to the suppression of lung inflammation. Lung function improved with roflumilast treatment and in some studies, the reduction in exacerbations was substantial and statistically significant. Notably, this effect appeared to be greatest in the subgroup of patients with more severe disease and more severe exacerbations. The evaluation of roflumilast safety largely centers on gastrointestinal adverse events, with diarrhea, nausea, and weight loss occurring more frequently with the drug than placebo. If approved for general use, we expect roflumilast to find its role initially as a substitute for inhaled corticosteroids in the maintenance treatment of severe and very severe disease, particularly in patients who have frequent acute exacerbations, and perhaps as a supplementary drug when symptoms are not adequately controlled by current conventional COPD therapy. ©
KW - Chronic obstructive pulmonary disease
KW - Inflammation
KW - Phosphodiesterase 4
KW - Roflumilast
UR - http://www.scopus.com/inward/record.url?scp=77951287116&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77951287116&partnerID=8YFLogxK
U2 - 10.3109/15412551003758304
DO - 10.3109/15412551003758304
M3 - Review article
C2 - 20397815
AN - SCOPUS:77951287116
VL - 7
SP - 141
EP - 153
JO - COPD: Journal of Chronic Obstructive Pulmonary Disease
JF - COPD: Journal of Chronic Obstructive Pulmonary Disease
SN - 1541-2555
IS - 2
ER -