초록
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 $500{\mu}g$ daily. Methods: We retrospectively investigated 85 patients with COPD who had taken either $500{\mu}g$ roflumilast, or a starting dose of $250{\mu}g$ and then increased to $500{\mu}g$. 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 $250{\mu}g$ roflumilast to $500{\mu}g$, 43 (82.7%) successfully maintained the $500{\mu}g$ 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 $500{\mu}g$ 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.