• Henrik Watz, Nitin Bagul, Klaus F Rabe, Stephen Rennard, Vijay Kt Alagappan, Jonas Román, Axel Facius, and Peter Ma Calverley.
• Pulmonary Research Institute at LungenClinic Grosshansdorf, Airway Research Center North, German Center for Lung Research, Grosshansdorf, Germany.
• Int J Chron Obstruct Pulmon Dis. 2018 Jan 1; 13: 813-822.

BackgroundThe 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.MethodsIn 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.ResultsPatients 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.ConclusionA 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.

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