Bullous pemphigoid induced by dipeptidyl peptidase-4 (DPP-4) inhibitors: a pharmacovigilance-pharmacodynamic/pharmacokinetic assessment through an analysis of the vigibase®
Bullous pemphigoid induced by dipeptidyl peptidase-4 (DPP-4) inhibitors: a pharmacovigilance-pharmacodynamic/pharmacokinetic assessment through an analysis of the vigibase®
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DOI：
10.1080/14740338.2019.1668373
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发表时间：
2019-09-27
影响因子：
3.1
通讯作者：
Radice, Sonia
中科院分区：
文献类型：
--
作者：
Carnovale, Carla;Mazhar, Faizan;Radice, Sonia
目的：在VigiBase（R）中检查大疱性类天疱疮（BP）与二肽基肽酶-4抑制剂（DPP-4 i）的信号以及其药效学/药代动力学参数在BP发生中的潜在作用。方法：在VigiBase（R）中进行病例/非病例分析，以检查格列汀的BP信号[报告比值比（ROR）]。其次，作者进行了线性回归分析，以探索BP的DPP-4 i信号与其对不同靶酶（DPP-2、DPP-4、DPP-8和DPP-9）的亲和力及其分布容积（Vd）之间的相关性。结果：DPP-4 i具有显著的BP信号。合并DPP-4 i的ROR为179.48（95% CI：166.41-193.58）。最高ROR为teneliglitazone 975.04（801.70-1185.87），最低为沙格列汀18.9（11.5-30.9）。线性回归分析显示，BP信号与DPP-4的甘精胰岛素亲和力之间的线性相关性具有显著性趋势（斜率= 1.316 [-0.4385-3.21]，p = 0.067，R-2 = 0.40），但其他酶靶标和Vd均无显著性趋势。结论：研究结果表明，由于暴露于这些药物，在BP的发展中格列汀对DDP-4的选择性具有临床相关性。为了更好地理解这种相关性，需要进行未来的临床前和临床研究。
Objectives: To examine the signals of bullous pemphigoid (BP) with dipeptidyl peptidase-4 inhibitors (DPP-4i) in VigiBase (R) and the potential role of their pharmacodynamic/pharmacokinetic parameters in the occurrence of BP. Methods: Case/non-case analyses were performed in VigiBase (R) to examine the signal of BP [reporting odds ratio (ROR)] for gliptins. Secondly, the authors performed linear regression analyses to explore the association between DPP-4i signals for BP and their affinities toward different target enzymes (DPP-2, DPP-4, DPP-8, and DPP-9) and their volume of distribution (Vd). Results: A significant BP signal was found for DPP-4i. The ROR for pooled DPP-4i was 179.48 (95% CI: 166.41-193.58). The highest ROR was found for teneligliptin 975.04 (801.70-1185.87) and lowest for saxagliptin 18.9 (11.5-30.9). Linear regression analyses showed a considerable trend to significance for the linear correlation between the BP signal and gliptin affinity at DPP-4 (slope = 1.316 [-0.4385-3.21], p = 0.067, R-2 = 0.40) but not the other enzyme targets, nor for Vd. Conclusion: The findings suggest a clinical relevance of gliptins selectivity for DDP-4 in the development of BP as a result of exposure to these drugs. Future preclinical and clinical studies are needed for a better understanding of this correlation.