Carla Carnovale1, Faizan Mazhar1, Elena Arzenton2, Ugo Moretti2, Marco Pozzi3, Giulia Mosini1, Olivia Leoni4, Marco Scatigna5, Emilio Clementi1,3, Sonia Radice1. 1. Unit of Clinical Pharmacology Department of Biomedical and Clinical Sciences L. Sacco, "Luigi Sacco" University Hospital, Università di Milano , Milan , Italy. 2. Department of Diagnostics and Public Health, Section of Pharmacology, University of Verona , Verona , Italy. 3. Scientific Institute, IRCCS Eugenio Medea , Bosisio Parini , Lecco , Italy. 4. Regional Pharmacovigilance Center of Lombardy , Milan , Italy. 5. Specialisation School of Clinical Pharmacology and Toxicology, Università degli Studi di Milano , Milan , Italy.
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.
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.
Entities:
Keywords:
Dipeptidyl peptidase-4 inhibitors; VigiBase; bullous pemphigoid; diabetes; drug safety
Authors: Carla Carnovale; Vera Battini; Michele Gringeri; Marina Volonté; Maria Chiara Uboldi; Andrea Chiarenza; Giovanni Passalacqua Journal: World Allergy Organ J Date: 2022-07-02 Impact factor: 5.516