Bullous pemphigoid induced by dipeptidyl peptidase-4 (DPP-4) inhibitors: a pharmacovigilance-pharmacodynamic/pharmacokinetic assessment through an analysis of the vigibase®

Carla Carnovale, Faizan Mazhar, Elena Arzenton, Ugo Moretti, Marco Pozzi, Giulia Mosini, Olivia Leoni, Marco Scatigna, Emilio Clementi, Sonia Radice

Research output: Contribution to journalArticle

Abstract

Objectives: To examine the signals of bullous pemphigoid (BP) with dipeptidyl peptidase-4 inhibitors (DPP-4i) in VigiBase® and the potential role of their pharmacodynamic/pharmacokinetic parameters in the occurrence of BP. Methods: Case/non-case analyses were performed in VigiBase® 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, R2 = 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.

Original languageEnglish
Pages (from-to)1099-1108
Number of pages10
JournalExpert Opinion on Drug Safety
Volume18
Issue number11
DOIs
Publication statusPublished - Nov 1 2019

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Keywords

  • bullous pemphigoid
  • diabetes
  • Dipeptidyl peptidase-4 inhibitors
  • drug safety
  • VigiBase

ASJC Scopus subject areas

  • Pharmacology (medical)

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