Incidence of Adverse Effects and Discontinuation Rate between Patients Receiving 250 Micrograms and 500 Micrograms of Roflumilast: A Comparative Study

Abstract

Background: Roflumilast is the only approved oral phosphodiesterase-4 inhibitor for the treatment of severe chronic obstructive pulmonary disease (COPD) in patients with chronic bronchitis and a history of frequent exacerbations. The purpose of this study was to examine the incidence of adverse effects associated with roflumilast treatment in a real-world setting. Further, we compared the incidence of adverse effects and the discontinuation rate among patients receiving different doses.

Methods: We identified all outpatients diagnosed with COPD at Seoul St. Mary's Hospital between May 2011 and September 2016 and retrospectively reviewed their medical records. Roflumilast was prescribed to patients in doses of 500 μg and 250 μg.

Results: A total of 269 COPD patients were prescribed roflumilast in our hospital during the study period. Among them, 178 patients were treated with 500 μg and 91 patients were treated with 250 μg. The incidence of adverse effects was 38.2% in the 500 μg group and 25.3% in the 250 μg group (p=0.034). The discontinuation rate of roflumilast was 41.6% (n=74) in the 500 μg group and 23.1% (n=21) in the 250 μg group (p=0.003). When adjusted by age, sex, smoking status, and lung function, 500 μg dose was significantly associated with the discontinuation of roflumilast (odds ratio, 2.87; p<0.001).

Conclusion: There was a lower incidence of adverse effects and discontinuation among patients treated with 250 μg compared with 500 μg dose. Further studies regarding the optimal dose of roflumilast are required.

Keywords: Adverse Effects; Pulmonary Disease, Chronic Obstructive; Roflumilast; Safety.

Figure 1. Flow diagram of the study. BDR: bronchodilator responsiveness; FEV₁: forced expiratory volume in 1 second; FVC: forced vital capacity.

Figure 2. Comparison of 500 µg roflumilast and 250 µg roflumilast treatment. (A) Comparison of the side effects of roflumilast. The incidence of adverse effects was significantly higher in patients in the 500 µg treatment group (p=0.034). (B) Comparison of the discontinuation of roflumilast. The discontinuation rate was significantly higher in patients in the 500 µg treatment group (p=0.003). (C) Comparison of the severe exacerbation of roflumilast. There was no significant difference in severe exacerbation rate (p=0.635).

Figure 3. Proportion of patients who continued with roflumilast. (A) Survival curve for the continuation of roflumilast. (B) Survival curve for the continuation of roflumilast after adjustment by age, sex, smoking status, and lung function.