Use of a 4-week up-titration regimen of roflumilast in patients with severe COPD

Henrik Watz, Nitin Bagul, Klaus F. Rabe, Stephen Rennard, Vijay K.T. Alagappan, Jonas Román, Axel Facius, Peter M.A. Calverley

Research output: Contribution to journalArticlepeer-review

21 Scopus citations


Background: The oral selective phosphodiesterase-4 inhibitor roflumilast (ROF) reduces exacerbations in patients with severe COPD. Adverse events (AEs) can cause early ROF discontinuation. Alternative dosing strategies may help patients continue their therapy. Methods: In this multicenter, double-blind trial, 1,321 patients with severe COPD were randomized 1:1:1 to 4 weeks’ treatment with ROF 250 µg once daily (OD), 500 µg every other day (EOD), or 500 µg OD, each followed by ROF 500 µg OD for 8 weeks, plus standard therapy. The primary end point was the percentage of patients prematurely discontinuing study treatment. Results: Patients in the 250 µg OD/500 µg OD group had significantly fewer treatment discontinuations (odds ratio [OR] 0.66 [95% CI 0.47–0.93], p=0.017) and lower rates of AEs of interest such as diarrhea, nausea, headache, decreased appetite, insomnia and abdominal pain (OR 0.63 [95% CI 0.47–0.83], p=0.001) compared with those in the 500 µg OD group. Although rates of discontinuation and AEs of interest were numerically lower with ROF 500 µg EOD/500 µg OD, the difference was not significant (OR 0.76, p=0.114, and OR 0.78, p=0.091, respectively) compared with ROF 500 µg OD. Conclusion: A dose of ROF 250 µg OD for 4 weeks before escalation to the approved maintenance dose of 500 µg OD resulted in reduced treatment discontinuation and improved tolerability.

Original languageEnglish (US)
Pages (from-to)813-822
Number of pages10
JournalInternational Journal of COPD
StatePublished - Mar 6 2018


  • Adverse event
  • COPD
  • Discontinuation
  • Roflumilast

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Health Policy
  • Public Health, Environmental and Occupational Health


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