Alispahic Imane Achir, Sørensen Rikke, Eklöf Josefin, Sivapalan Pradeesh, Løkke Anders, Seersholm Niels, Vestergaard Jakob Hedemark, Jensen Jens-Ulrik Stæhr
Department of Internal Medicine, Respiratory Medicine Section, Herlev and Gentofte Hospital, University Hospital of Copenhagen, 2900 Copenhagen, Denmark.
Department of Cardiology, Rigshospitalet, University Hospital of Copenhagen, University of Copenhagen, 2100 Copenhagen, Denmark.
J Clin Med. 2020 May 12;9(5):1442. doi: 10.3390/jcm9051442.
Roflumilast is given as an add-on to inhalation medication in patients with chronic obstructive pulmonary disease (COPD) and chronic bronchitis. Animal experiments have documented deleterious effects of roflumilast in bacterial infections, but trials have not reported the risk of bacterial infections in patients. The objective of this study is to determine, among outpatients with severe COPD in a two-year follow-up period, the risk of hospitalization-requiring pneumonia, severe acute exacerbation in COPD (AECOPD-hosp), and death. Patients with COPD using roflumilast (roflumilast users) were compared to a propensity score-matched COPD control group not using roflumilast (non-roflumilast users). Roflumilast users had an increased 2-year risk of hospitalization-requiring pneumonia (HR 1.5, 95% CI 1.3 to 1.8, value < 0.0001) compared to controls, and of AECOPD-Hosp (hazard ratio(HR) 1.6, 95%, confidence interval (CI) 1.5 to 1.8, value < 0.0001) and. When adding an active comparator (theophylline) as a matching variable, the signal was largely unchanged. In conclusion, roflumilast was associated with an increased number of hospitalizations for pneumonia and for AECOPD. Since trials have not reported risks of bacterial complications and data regarding severe exacerbations in roflumilast users are sparse and diverging, these data are concerning. Trials focused on the risk of pneumonia, AECOPD, and other bacterial infections in roflumilast users are needed urgently.
罗氟司特作为慢性阻塞性肺疾病（COPD）和慢性支气管炎患者吸入药物的附加治疗药物。动物实验已证明罗氟司特在细菌感染中有有害作用，但试验尚未报告患者发生细菌感染的风险。本研究的目的是在重度COPD门诊患者的两年随访期内，确定需要住院治疗的肺炎、COPD严重急性加重（AECOPD - hosp）和死亡的风险。将使用罗氟司特的COPD患者（罗氟司特使用者）与倾向评分匹配的未使用罗氟司特的COPD对照组（非罗氟司特使用者）进行比较。与对照组相比，罗氟司特使用者发生需要住院治疗的肺炎的2年风险增加（风险比[HR] 1.5，95%置信区间[CI] 1.3至1.8，P值<0.0001），发生AECOPD - Hosp的风险也增加（风险比[HR] 1.6，95%置信区间[CI] 1.5至1.8，P值<0.0001）。当添加活性对照药（茶碱）作为匹配变量时，该信号基本未变。总之，罗氟司特与肺炎和AECOPD的住院次数增加有关。由于试验未报告细菌并发症的风险，且关于罗氟司特使用者严重加重的数据稀少且存在分歧，这些数据令人担忧。迫切需要针对罗氟司特使用者的肺炎、AECOPD和其他细菌感染风险进行试验。
