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 language | English |
|---|---|
| Pages (from-to) | 1099-1108 |
| Number of pages | 10 |
| Journal | Expert Opinion on Drug Safety |
| Volume | 18 |
| Issue number | 11 |
| DOIs | |
| Publication status | Published - Nov 1 2019 |
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Keywords
- bullous pemphigoid
- diabetes
- Dipeptidyl peptidase-4 inhibitors
- drug safety
- VigiBase
ASJC Scopus subject areas
- Pharmacology (medical)
Cite this
Bullous pemphigoid induced by dipeptidyl peptidase-4 (DPP-4) inhibitors : a pharmacovigilance-pharmacodynamic/pharmacokinetic assessment through an analysis of the vigibase®. / Carnovale, Carla; Mazhar, Faizan; Arzenton, Elena; Moretti, Ugo; Pozzi, Marco; Mosini, Giulia; Leoni, Olivia; Scatigna, Marco; Clementi, Emilio; Radice, Sonia.
In: Expert Opinion on Drug Safety, Vol. 18, No. 11, 01.11.2019, p. 1099-1108.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Bullous pemphigoid induced by dipeptidyl peptidase-4 (DPP-4) inhibitors
T2 - a pharmacovigilance-pharmacodynamic/pharmacokinetic assessment through an analysis of the vigibase®
AU - Carnovale, Carla
AU - Mazhar, Faizan
AU - Arzenton, Elena
AU - Moretti, Ugo
AU - Pozzi, Marco
AU - Mosini, Giulia
AU - Leoni, Olivia
AU - Scatigna, Marco
AU - Clementi, Emilio
AU - Radice, Sonia
PY - 2019/11/1
Y1 - 2019/11/1
N2 - 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.
AB - 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.
KW - bullous pemphigoid
KW - diabetes
KW - Dipeptidyl peptidase-4 inhibitors
KW - drug safety
KW - VigiBase
UR - http://www.scopus.com/inward/record.url?scp=85073183302&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85073183302&partnerID=8YFLogxK
U2 - 10.1080/14740338.2019.1668373
DO - 10.1080/14740338.2019.1668373
M3 - Article
C2 - 31519110
AN - SCOPUS:85073183302
VL - 18
SP - 1099
EP - 1108
JO - Expert Opinion on Drug Safety
JF - Expert Opinion on Drug Safety
SN - 1474-0338
IS - 11
ER -