Effect of a Dose-Escalation Regimen for Improving Adherence to Roflumilast in Patients with Chronic Obstructive Pulmonary Disease

Background: The adverse effects of the phosphodiesterase-4 inhibitor roflumilast, appear to be more frequent in clinical practice than what was observed in chronic obstructive pulmonary disease (COPD) clinical trials. Thus, we designed this study to determine whether adverse effects could be reduced by starting roflumilast at half the dose, and then increasing a few weeks later to 500 g daily. Methods: We retrospectively investigated 85 patients with COPD who had taken either 500 g roflumilast, or a starting dose of 250 g and then increased to 500 g. We analyzed all adverse events and assessed differences between patients who continued taking the drug after dose escalation and those who had stopped. Results: Adverse events were reported by 22 of the 85 patients (25.9%). The most common adverse event was diarrhea (10.6%). Of the 52 patients who had increased from a starting dose of 250 g roflumilast to 500 g, 43 (82.7%) successfully maintained the 500 g roflumilast dose. No difference in factors likely to affect the risk of adverse effects, was detected between the dose-escalated and the discontinued groups. Of the 26 patients who started with the 500 g roflumilast regimen, seven (26.9%) discontinued because of adverse effects. There was no statistically significant difference in discontinuation rate between the dose-escalated and the control groups (p=0.22). Conclusion: Escalating the roflumilast dose may reduce treatment-related adverse effects and improve tolerance to the full dose. This study suggests that the dose-escalated regimen reduced the rate of discontinuation. However, longer-term and larger-scale studies are needed to support the full benefit of a dose escalation strategy.