Background: Frequent development of adverse events and consequent low adherence are major barriers in the wide use of roflumilast. Asian patients may be more susceptible to adverse events due to low BMI. In this study, we aimed to determine if a dose-escalation strategy is useful to improve the drug adherence rate.
Methods: This was a randomized, prospective, open-label, single-blind study to compare the adherence rate to roflumilast according to a dose-escalation or conventional dose strategy in patients with COPD in South Korea. Patients were randomized into two groups (1:1), either roflumilast 500 μg once daily for 12 weeks or roflumilast 250 μg once daily for 4 weeks, and then 500 μg for 12 weeks. The primary outcome was the percentage of patients prematurely discontinuing roflumilast due to adverse events.
Results: A total of 55 patients were randomly assigned to either a conventional-dose group (n=28) or a dose-escalation group (n=27). Discontinuation rates of roflumilast due to adverse events were 46.4% for the conventional-dose group and 59.3% for the dose-escalation group. The median time to discontinuation was not different between groups (58 days for the conventional-dose group, 56 days for the dose-escalation group, p=0.629). In a multivariate analysis, older age was a significant risk factor for drug discontinuation.
Conclusion: High discontinuation rates of roflumilast were observed in both groups regardless of the dose-escalation strategy. The frequent discontinuation suggests that the dose-escalation strategy may not be useful in Asian patients.
Clinical trial: This study is registered at www.ClinicalTrials.gov with identifier number NCT02018432.
Keywords: COPD; adherence; roflumilast.