Bullous Pemphigoid and Dipeptidyl Peptidase 4 Inhibitors: A Disproportionality Analysis Based on the Japanese Adverse Drug Event Report Database.

Abstract

Bullous pemphigoid (BP) is a rare autoimmune blistering skin disease. Although previous case reports and two disproportionality analyses of European populations have suggested associations between dipeptideyl peptidase 4 (DPP-4) inhibitor use and BP (1–3), the involvement of race, antidiabetes drugs, sex, age, and other risk factors in BP induced by DPP-4 inhibitors has not yet been evaluated. We conducted disproportionality analysis using the Japanese Adverse Drug Event Report (JADER) database, which contains all pharmacovigilance data that have been spontaneously reported to the Pharmaceuticals and Medical Devices Agency (PMDA) since April 2004. As of June 2017, the database contained 454,027 reports of adverse drug reactions. For this study, data were downloaded from the PMDA website (http://www.pmda.go.jp). Potential signals of DPP-4 inhibitors or other drugs with BP were assessed with categories using the reporting odds ratio (ROR), which is an established parameter in pharmacovigilance research. An ROR was calculated using a two-by-two contingency table (4). We examined DPP-4 inhibitors (alogliptin, anagliptin, linagliptin, omarigliptin, saxagliptin, sitagliptin, trelagliptin, teneligliptin, and vildagliptin), other antihyperglycemia drug classes (sulfonylureas, biguanides, α-glucosidase inhibitors [α-GIs], glinides, glucagon-like peptide 1 receptor agonists [GLP-1 RAs], sodium–glucose cotransporter 2 inhibitors [SGLT2is], thiazolidines, and any kind of insulins), other drugs that are reported as causal reagents for …