(A-256) Identifying Potential Drug Triggers for Bullous Pemphigoid: A Disproportionality Analysis of the FDA Adverse Event Reporting System and Review of Case Reports

Background: Bullous pemphigoid (BP) is an autoimmune subepithelial disease characterized by the generation of pruritus followed by urticarial plaques and finally bullae on the skin and mucosa.

Objectives: The aim of the study is to investigate the potential association between drugs and the development of bullous pemphigoid (BP).

Methods: A retrospective case study was conducted using spontaneous reports of drug-induced bullous pemphigus from the FDA Adverse Event Reporting System (FAERS) database between Q1/ 2004 to Q3/2024. Then, in agreement with the MedDRA terminology, reports of AE were identified by the preferred term (PT) “Pemphigoid” (PT code: 10034277). A disproportionality analysis was performed by calculating the Proportional Reporting Ratio (PRR), Reporting Odds Ratio (ROR), and the Information Component (IC) to identify signals of drug-induced bullous pemphigus. Additionally, a review of literature search was conducted in PubMed and Scopus to review case reports of drug-induced bullous pemphigoid.

Results: The total number of reported pemphigoid cases was 3608. Males accounted for 53% (1310 cases) and patients over 65 years accounted for 62.5% (1544 cases). Using disproportionality analysis, 61 signals were identified for drug-induced bullous pemphigoid (BP). The most frequently reported causative drug was metformin (596 cases), vildagliptin (406 cases), nivolumab (376 cases), furosemide (301 cases), linagliptin (220 cases), sitagliptin (189 cases), pembrolizumab (157 cases), and hydrochlorothiazide (142 cases). Vildagliptin [PRR = 295.8 (χ2 = 105875.8), LB ROR = 287.2, IC025 = 7.5], Dapsone [PRR = 20.7 (χ2 = 522.3), LB ROR = 14.4, IC025 = 3.4], Furosemide diuretics [PRR = 7.2 (χ2 = 1466.0), LB ROR = 6.4, IC025 = 2.6], and nivolumab [PRR =31.5 (χ2 = 9952.9), LB ROR = 28.5, IC025 = 4.6] were the strong signals identified for drug-induced bullous pemphigoid among antidiabetics, antimicrobials, diuretics, immune checkpoint inhibitors, and biological agents. A systematic literature review of PubMed and Scopus databases identified 106 published case reports of drug-induced bullous pemphigoid, which provides further evidence supporting a potential association between bullous pemphigoid and various drug classes, such as antidiabetics, antimicrobials, diuretics, immune checkpoint inhibitors, and biological agents.

Conclusions: This study highlights the growing body of evidence linking various medications, such as metformin, vildagliptin, nivolumab, furosemide, linagliptin, sitagliptin, pembrolizumab, hydrochlorothiazide and many other medications from the various drug classes, such as antidiabetics, antimicrobials, diuretics, immune checkpoint inhibitors, and biological agents to the development of bullous pemphigoid.