Department of Pharmacology, Faculty of Medicine, National Autonomous University of Mexico, Mexico City, Mexico.
Centre for Drug Safety (CESME), Faculty of Medicine, Valladolid University, Valladolid, Spain.
Int J Clin Pharm. 2020 Apr;42(2):713-720. doi: 10.1007/s11096-020-01003-6. Epub 2020 Mar 5.
Background Bullous pemphigoid has been associated to dipeptidase-4 inhibitors. Objectives Addressing the potential Bullous pemphigoid-dipeptidase-4 inhibitors association based on pharmacovigilance data currently available in Spain in order to obtain a composite disproportionality estimator from all the data generated by the case-non case studies conducted to this date. Setting The Spanish Pharmacovigilance System for Human Use Drugs database. Method Case-non case study based on the Spanish Pharmacovigilance System for Human Use Drugs notifications submitted between 2007 and 2018 (n = 169,280), using the Medical Dictionary for Regulatory Activities term (Preferred Term) 'pemphigoid' for sitagliptin, vildagliptin, saxagliptin, linagliptin, and alogliptin (n = 1952). As negative control, we used acetaminophen, while furosemide was the positive control. A pooled reported odds ratio analysis in the French, Japanese, and Spanish national pharmacovigilance databases was performed. On The Spanish Pharmacovigilance System for Human Use Drugs, we conducted a bullous pemphigoid-metformin association analysis within the period 1982-2018. Main outcome measure Adverse reaction cases in pharmacovigilance databases and the disproportionality through the reporting odds ratio. Results Within The Spanish Pharmacovigilance System for Human Use Drugs, we found 45 cases of bullous pemphigoid in dipeptidase-4 inhibitors patients. Median age was 77 years (range 72-82). The median latency period was 7 months (range 0.23-86). The Bullous pemphigoid-dipeptidase-4 inhibitors association was established with a reporting odd ratio = 70.0 (95% confidence intervals 49.1-10.1). In the combined analysis of the three aforementioned pharmacovigilance databases, the pooled reporting odd ratio was 81.0 (95% confidence intervals 69.5-94.4). Conclusion The composite estimator for the three national pharmacovigilance databases yields clear evidence of a Bullous pemphigoid-dipeptidase-4 inhibitors association, which was statistically significant for both the pharmacological class as a whole and each of the dipeptidase-4 inhibitors agents under investigation. Metformin's role in the incidence of bullous pemphigoid appeared casual rather than causal. No differences between Caucasian and Asian populations were noted.
大疱性类天疱疮与二肽基肽酶-4 抑制剂有关。目的：根据目前在西班牙可用的药物警戒数据，探讨大疱性类天疱疮与二肽基肽酶-4 抑制剂之间的潜在关联，以便从迄今为止进行的病例对照研究中生成所有数据的综合比例不平衡估计值。设置：西班牙人用药物药物警戒系统。方法：基于西班牙人用药物药物警戒系统在 2007 年至 2018 年期间提交的通知（n=169280）进行病例对照研究，使用监管活动医学词典术语（首选术语）“大疱性类天疱疮”来表示西他列汀、维格列汀、沙格列汀、利格列汀和阿格列汀（n=1952）。作为阴性对照，我们使用对乙酰氨基酚，而呋塞米为阳性对照。在法国、日本和西班牙国家药物警戒数据库中进行了 pooled reported odds ratio 分析。在西班牙人用药物药物警戒系统中，我们在 1982 年至 2018 年期间对二肽基肽酶-4 抑制剂患者中的大疱性类天疱疮-二甲双胍关联进行了分析。主要观察指标：药物警戒数据库中的不良反应病例和通过报告比值比进行的比例不平衡。结果：在西班牙人用药物药物警戒系统中，我们发现 45 例大疱性类天疱疮患者使用二肽基肽酶-4 抑制剂。中位年龄为 77 岁（范围 72-82）。中位潜伏期为 7 个月（范围 0.23-86）。大疱性类天疱疮与二肽基肽酶-4 抑制剂之间的关联采用报告比值比=70.0（95%置信区间 49.1-10.1）建立。在上述三个药物警戒数据库的联合分析中，pooled reported odds ratio 为 81.0（95%置信区间 69.5-94.4）。结论：三个国家药物警戒数据库的综合估计值提供了大疱性类天疱疮与二肽基肽酶-4 抑制剂之间关联的明确证据，该关联在整个药物类别以及正在研究的每个二肽基肽酶-4 抑制剂药物方面均具有统计学意义。二甲双胍在大疱性类天疱疮发病中的作用似乎是偶然的，而不是因果关系。未观察到白种人和亚洲人群之间的差异。
