Table 1_A real-world disproportionality analysis of roflumilast using the US food and drug administration adverse event reporting system data.xlsx

IntroductionRoflumilast, a selective phosphodiesterase-4 inhibitor, is prescribed to reduce exacerbations in severe COPD, but its real-world safety profile remains insufficiently characterized.
MethodsWe conducted a retrospective pharmacovigilance study using the FDA Adverse Event Reporting System (FAERS). Reports from 2004 to 2025Q1 listing roflumilast as the primary suspect were extracted, deduplicated, and analyzed. Disproportionality analysis employed four algorithms—Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-item Gamma Poisson Shrinker (MGPS). Safety signals were defined by established thresholds. Time-to-onset and Weibull modeling were applied to assess temporal patterns.
ResultsA total of 3,140 reports were identified, primarily involving older COPD patients. The median time-to-onset was 4 days (IQR 0–34), with 72% occurring within 30 days. Thirty Preferred Terms met signal criteria. Frequent signals included diarrhoea, weight decreased, nausea, dyspnoea, insomnia, and headache. Psychiatric events such as depression and suicidal ideation were notable. The strongest disproportionality was observed for gastroduodenal ulcer (ROR 47.1) and COPD (ROR 25.7). System Organ Class enrichment was most evident in gastrointestinal, psychiatric, and respiratory disorders.
Discussion/ConclusionThis real-world analysis confirms roflumilast’s established adverse effects (gastrointestinal upset, weight loss, insomnia) and highlights concerning psychiatric signals. Most events occurred early, underscoring the need for close monitoring during treatment initiation. The use of multiple disproportionality methods enhances signal detection robustness and supports ongoing pharmacovigilance in clinical practice.

引言
罗氟司特（roflumilast）是一种选择性磷酸二酯酶4抑制剂（selective phosphodiesterase-4 inhibitor），临床用于降低重度慢性阻塞性肺疾病（Chronic Obstructive Pulmonary Disease, COPD）患者的急性加重风险，但目前其真实世界安全性特征仍未得到充分阐明。

方法
本研究采用美国食品药品监督管理局不良事件报告系统（FDA Adverse Event Reporting System, FAERS）开展一项回顾性药物警戒研究。提取并去重了2004年至2025年第一季度中以罗氟司特为主要可疑药物的不良事件报告，并进行分析。采用四种算法开展不均衡性分析：报告比值比（Reporting Odds Ratio, ROR）、比例报告比（Proportional Reporting Ratio, PRR）、贝叶斯置信传播神经网络（Bayesian Confidence Propagation Neural Network, BCPNN）以及多项目伽马泊松收缩器（Multi-item Gamma Poisson Shrinker, MGPS）。安全性信号以既定阈值进行界定。采用发病时间分析与威布尔（Weibull）模型评估不良事件的时间分布特征。

结果
共纳入3140份不良事件报告，研究对象以老年慢性阻塞性肺疾病患者为主。不良事件中位发病时间为4天（四分位间距0~34天），其中72%的事件发生在用药后30天内。共有30项首选术语（Preferred Terms）符合安全性信号判定标准。高频信号包括腹泻、体重下降、恶心、呼吸困难、失眠及头痛。值得关注的精神系统不良事件包括抑郁与自杀意念。胃肠十二指肠溃疡（ROR=47.1）与慢性阻塞性肺疾病（ROR=25.7）的不均衡性最为显著。系统器官分类（System Organ Class, SOC）富集现象在消化系统、精神系统及呼吸系统疾病中最为明显。

讨论与结论
本项真实世界研究证实了罗氟司特已知的不良反应（胃肠道不适、体重减轻、失眠），同时揭示了需关注的精神系统安全性信号。多数不良事件发生于用药早期，提示在治疗起始阶段需加强密切监测。采用多种不均衡性分析方法可提升信号检测的稳健性，可为临床实践中的持续药物警戒工作提供支撑。