Risk factors for the discontinuation of roflumilast in patients with chronic obstructive pulmonary disease

Abstract

Introduction: Roflumilast is a phosphodiesterase-4 inhibitor, which can decrease exacerbation in patients with chronic obstructive pulmonary disease (COPD). However, adverse effects are a major barrier to medication use, and little is known regarding the risk factors for discontinuation of roflumilast in COPD patients.

Method: A search of the clinical databases identified all patients who were prescribed roflumilast between December 2012 and April 2015 in the four hospitals of The Catholic University of Korea, Korea. The study subjects were limited to patients who had taken 500 μg of roflumilast. We studied the factors associated with drug discontinuation and drug adverse events by univariate and multivariate analyses.

Results: Among 154 eligible patients, 54 (35.1%) discontinued their roflumilast prescription. Most patients were elderly, male, current or former smokers, and had moderate-to-severe airflow limitation. Low-body mass index (BMI) patients were more likely to undergo drug discontinuation (1-unit decrease in BMI: odds ratio [OR] =1.165, p=0.006; BMI <23 kg/m²: OR =2.960, p=0.004). Fifty-five patients (35.7%) had adverse events. Loss of appetite, diarrhea, nausea, headache, and weight loss were the most frequent adverse events. Low-BMI patients were more likely to experience adverse events (1-unit decrease in BMI: OR =1.151, p=0.010; BMI <23 kg/m²: OR =2.644, p=0.009).

Conclusions: The patient discontinuation and adverse events rates in this study were higher than in previous randomized controlled studies. Discontinuation of roflumilast in ethnic Koreans is more likely to occur in low-BMI patients. In a clinical setting, low-BMI patients can more easily discontinue roflumilast; clinicians should, therefore, provide greater care for these patients.

Keywords: adverse event; body mass index; chronic obstructive pulmonary disease; phosphodiesterase-4 inhibitor.

Figure 1

Process of patient recruitment. Note: A total of 270 patients receiving new-onset roflumilast prescriptions between 2012 and 2015 were selected, and 16 dose-unknown patients, 93 patients treated with 250 μg of roflumilast, and 7 BMI-unknown patients were excluded. Abbreviation: BMI, body mass index.

Figure 2

Rates of roflumilast discontinuation by BMI group. Notes: In the underweight and normal BMI groups, the rates of roflumilast discontinuation were 41.4% and 45.4%, respectively. On the other hand, in the overweight and obese BMI groups, the roflumilast discontinuation rates were 22.5% and 19.0%, respectively. Abbreviation: BMI, body mass index.

Figure 3

Rates of roflumilast adverse events by BMI group. Notes: In the underweight and normal BMI groups, the roflumilast adverse events rates were 41.4% and 45.3%, respectively. On the other hand, in the overweight and obese BMI groups, the roflumilast adverse events rates were 27.5% and 14.3%, respectively. Abbreviation: BMI, body mass index.