title: Benefits and harms of roflumilast in moderate to severe COPD.
abstract: BACKGROUND
  Roflumilast, a phosphodiesterase 4 inhibitor, has been approved for the prevention of chronic obstructive pulmonary disease (COPD) exacerbations. It is unclear which patients will have a favourable benefit-harm balance with roflumilast. Our aim was to quantitatively assess the benefits and harms of roflumilast (500 µg/day) compared with placebo.
  
  
  METHODS
  We used summary data released by the US Food and Drug Administration to estimate the treatment effects of roflumilast. Data from trials and observational studies were used to estimate the baseline risks for COPD exacerbations and gastrointestinal, neurological and psychiatric harms associated with roflumilast. Using simulation, we calculated the probability that roflumilast provides net benefit. We examined the impacts of different baseline risks for exacerbations and the severity of exacerbations, and varied weights (ie, relative importance) for outcomes and treated death as a competing risk in the analyses.
  
  
  RESULTS
  The probability that roflumilast provides net benefit approximates 0% across different age categories of men and women with varying baseline risks for exacerbations. Using different weights for outcomes did not change the probability that roflumilast provides a net benefit. Only in the sensitivity analysis restricted to the prevention of severe exacerbations was there a probability of >50% that roflumilast provides a net benefit if the baseline risk of having at least one severe exacerbation per year exceeds 22%.
  
  
  CONCLUSIONS
  Our results suggest that roflumilast only provides a net benefit to patients at a high risk of severe exacerbations. Guideline developers should consider different recommendations for patients with COPD at different baseline risks for exacerbations.
authors.affiliation: Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, USA.
authors.forename: Tsung
authors.initials: T
authors.lastname: Yu
authors.affiliation: Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, USA.
authors.forename: Kevin
authors.initials: K
authors.lastname: Fain
authors.affiliation: Division of Geriatric Medicine and Gerontology, Johns Hopkins School of Medicine, Baltimore, USA.
authors.forename: Cynthia M
authors.initials: CM
authors.lastname: Boyd
authors.affiliation: Division of General Internal Medicine, Johns Hopkins School of Medicine, Baltimore, USA.
authors.forename: Sonal
authors.initials: S
authors.lastname: Singh
authors.affiliation: Division of Geriatric Medicine and Gerontology, Johns Hopkins School of Medicine, Baltimore, USA Division of Geriatric Medicine and Gerontology, Michigan State University, Grand Rapids, USA.
authors.forename: Carlos O
authors.initials: CO
authors.lastname: Weiss
authors.affiliation: Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, USA.
authors.forename: Tianjing
authors.initials: T
authors.lastname: Li
authors.affiliation: Division of Geriatric Medicine and Gerontology, Johns Hopkins School of Medicine, Baltimore, USA.
authors.forename: Ravi
authors.initials: R
authors.lastname: Varadhan
authors.affiliation: Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, USA Institute of Social and Preventive Medicine, University of Zurich, Zurich, Switzerland.
authors.forename: Milo A
authors.initials: MA
authors.lastname: Puhan
mesh_terms: D000368:Aged; D000631:Aminopyridines / Q000009:adverse effects / Q000627:therapeutic use*; D001549:Benzamides / Q000009:adverse effects / Q000627:therapeutic use*; D003521:Cyclopropanes / Q000009:adverse effects / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D058988:Phosphodiesterase 4 Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D010919:Placebos; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000503:physiopathology; D018570:Risk Assessment
chemical_list: D000631:Aminopyridines; D001549:Benzamides; D003521:Cyclopropanes; D058988:Phosphodiesterase 4 Inhibitors; D010919:Placebos; C424423:Roflumilast