title: Roflumilast in chronic obstructive pulmonary disease: evidence from large trials.
abstract: BACKGROUND
  Chronic inflammation plays a central role in chronic obstructive pulmonary disease (COPD). Suppression of the inflammatory response is a logical approach to the treatment of COPD. Corticosteroids are highly effective as an anti-inflammatory treatment, but patients with COPD are poorly responsive to these drugs. The phosphodiesterase (PDE)-4 isoenzyme is a major therapeutic target in COPD because its inhibition increases intracellular cAMP concentrations, which ultimately results in reduction of cellular inflammatory activity. At present roflumilast is the most advanced PDE-4 inhibitor undergoing clinical trials for COPD.
  
  
  METHODS
  In this paper, we describe the importance of roflumilast as an anti-inflammatory drug and critically review the results of four large trials with roflumilast in COPD (NCT00297102, NCT00297115, NCT00313209, NCT00424268).
  
  
  RESULTS
  An unbiased description of trials that have explored the therapeutic effects of roflumilast in COPD.
  
  
  CONCLUSIONS
  At the moment, roflumilast should only be considered as a second-line treatment, and the exact indication remains to be determined. Apparently, it should be reserved for patients who have frequent exacerbations despite treatment with inhaled bronchodilators. However, considering the high risk of adverse events induced by this drug, the published evidence seems to indicate limiting its use to the treatment of patients suffering from very severe COPD.
authors.affiliation: Unità di Farmacologia Clinica Respiratoria, Dipartimento di Medicina Interna, Università di Roma Tor Vergata, Via Montpellier 1, 00133 Rome, Italy. mario.cazzola@uniroma2.it
authors.forename: Mario
authors.initials: M
authors.lastname: Cazzola
authors.forename: Stefano
authors.initials: S
authors.lastname: Picciolo
authors.forename: Maria G
authors.initials: MG
authors.lastname: Matera
mesh_terms: D000280:Administration, Inhalation; D000284:Administration, Oral; D000631:Aminopyridines / Q000009:adverse effects* / Q000627:therapeutic use; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D001549:Benzamides / Q000009:adverse effects* / Q000627:therapeutic use; D001993:Bronchodilator Agents / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D003521:Cyclopropanes / Q000009:adverse effects / Q000627:therapeutic use; D004334:Drug Administration Schedule; D005541:Forced Expiratory Volume / Q000187:drug effects*; D006801:Humans; D008168:Lung; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy*; D011788:Quality of Life; D012720:Severity of Illness Index; D000074606:Smoking Prevention; D016896:Treatment Outcome
chemical_list: D000631:Aminopyridines; D000893:Anti-Inflammatory Agents; D001549:Benzamides; D001993:Bronchodilator Agents; D003521:Cyclopropanes; D010726:Phosphodiesterase Inhibitors; C424423:Roflumilast