The association of pancreatitis with antidiabetic drug use: gaining insight through the FDA pharmacovigilance database
The association of pancreatitis with antidiabetic drug use: gaining insight through the FDA pharmacovigilance database
复制标题
DOI：
10.1007/s00592-011-0340-7
复制
发表时间：
2013-08-01
影响因子：
3.8
通讯作者：
De Ponti, F.
中科院分区：
文献类型：
--
作者：
Raschi, E.;Piccinni, C.;De Ponti, F.
在糖尿病患者中，疾病本身、合并症和药物（包括作用于肠促胰岛素系统的新型药物）均与胰腺炎相关，且数据存在争议。我们调查了公开可用的FDA不良事件报告系统（FDA_AERS）数据库，以深入了解抗糖尿病药物与胰腺炎之间的可能关联。为此，对FDA_AERS数据库（2004-2009年期间）进行了病例/非病例回顾性分析。根据国际医学用语词典（MedDRA）术语，病例定义为胰腺炎报告。与降糖药相关的所有其他报告均视为非病例。计算报告比值比（ROR），以及相应的95%置信区间（CI）和Mantel-Haenszel校正的P值，作为一项指标，随后进行时间趋势分析。我们检索了86，938份与降糖药物相关的报告，对应于159，226种药物报告组合：2，625例病例和156，601例非病例。仅艾塞那肽（病例数，709; ROR，1.76; 95% CI，1.61-1.92; P（MH）< 0.001）和西格列汀（128; 1.86; 1.54-2.24; < 0.001）发现比例失调。对于艾塞那肽，在FDA警告后不久，2008年第一季度出现了显著的不良反应（ROR，1.24; 95% CI，1.10-1.40; P（MH）< 0.001）;对于西格列汀，在2008年第二季度出现了显著的不良反应（1.41; 1.05-1.90; 0.021）。该时间分析发现相关FDA警告对胰腺炎报告的显著影响（所谓的恶名偏倚），因此建议避免将药物警戒信号自动转换为警报。确切量化与抗糖尿病药物相关的胰腺炎风险值得通过基于特定疾病的登记进行评估。
In patients with diabetes, disease per se, co-morbidities and drugs, including novel agents acting on the incretin system, have all been associated with pancreatitis with controversial data. We investigated the publicly available FDA Adverse Event Reporting System (FDA_AERS) database to gain insight into the possible association between antidiabetic agents and pancreatitis. To this aim, a case/non-case method was retrospectively performed on the FDA_AERS database (2004-2009 period). Cases were defined as reports of pancreatitis according to the Medical Dictionary for Regulatory Activities (MedDRA) terminology. All other reports associated with antidiabetics were considered non-cases. The Reporting Odds Ratio (RORs), with corresponding 95% confidential interval (CI) and Mantel-Haenszel corrected P value, was calculated as a measure of disproportionality, with subsequent time-trend analysis. We retrieved 86,938 reports related to antidiabetics, corresponding to 159,226 drug-report combinations: 2,625 cases and 156,601 non-cases. Disproportionality was found only for exenatide (number of cases, 709; ROR, 1.76; 95% CI, 1.61-1.92; P (MH) < 0.001) and sitagliptin (128; 1.86; 1.54-2.24; < 0.001). For exenatide, significant disproportionality appeared in the first quarter of 2008 (ROR, 1.24; 95% CI, 1.10-1.40; P (MH) < 0.001), soon after the FDA alert; for sitagliptin in the second quarter of 2008 (1.41; 1.05-1.90; 0.021). This temporal analysis found a striking influence of relevant FDA warnings on reporting of pancreatitis (the so-called notoriety bias) and is, therefore, recommended to avoid transforming a pharmacovigilance signal of alert automatically into an alarm. The precise quantification of the risk of pancreatitis associated with antidiabetics deserves assessment through specific disease-based registries.