Abstract
Background/Objectives: Bullous pemphigoid (BP) is an autoimmune blistering skin disease. The association between dipeptidyl peptidase 4 inhibitors (DPP-4 inhibitors) and bullous pemphigoid (BP) has been studied in many countries; however, controversy has arisen from analyzing the related risk factors. The objectives of this study are to assess whether the association between DPP-4 inhibitors and bullous pemphigoid in EudraVigilance is statistically significant and to identify the presence of risk factors found in previous studies in a case/exposure group. Our results will be compared with those obtained from the Food and Drug Administration Adverse Event Reporting System database (FAERS). Methods: A case/control retrospective observational study was performed using data from the European database EudraVigilance. All reports from 2007 to 2024 (a total of 11,451,738 reports) were gathered and filtered by exposure to DPP-4 inhibitors and development of BP or lack thereof. Association was measured using reporting odds ratios with a 95% confidence interval, and Fisher's exact test was used to obtain p-values, assuming an alpha error of 0.05. Results: The results indicate an association between the consumption of DPP-4 inhibitors and the development of BP (with an odds ratio of 153.5; 95% confidence interval 144.1-163.5; ROR = (a/c)/(b/d); a: 1345 reports of BP associated with DPP-4i; c: 3870 reports of BP associated with other different drugs; b: 25,857 reports of other ADRs and DPP-4i; and d: 11,420,666 reports of ADRs associated with other drugs). The predominant factors in the case/exposure group were male gender (58.6%), age between 65 and 85 years (43.3%), medical history of type 2 diabetes mellitus (30.4%) and consumption of vildagliptin (44.2%). Similar results were found in a prior analysis of the FAERS database (2006-2020). Conclusions: This study provides evidence of the association between the consumption of gliptins and the development of BP. Disproportionality measures were estimated to be higher in the exposure group than in the positive controls. As such, BP could appear after several months of exposure, and dermatological monitoring is crucial.