Identifying potential drug triggers for bullous pemphigoid: a disproportionality analysis of the FDA adverse event reporting system and systematic review of case reports

Abstract

Objective: This study aimed to assess the potential risk of Bullous pemphigoid (BP) associated with antidiabetic agents, antimicrobials, diuretics, immune checkpoint inhibitors, and biological agents.

Research design and methods: A retrospective pharmacovigilance data analysis was conducted using the FDA Adverse Event Reporting System (FAERS) between Q1/2004 and Q3/2024. Disproportionality analyses, viz. Proportional Reporting Ratio (PRR), Reporting Odds Ratio (ROR), and Information Component (IC) were performed to identify signals of BP. Additionally, a literature review of case reports of BP was conducted in PubMed, Google Scholar, and Scopus.

Results: Disproportionality analysis identified 61 signals, and the following drugs exhibited the highest number of BP case associations: metformin (596 cases), vildagliptin (406 cases), nivolumab (376 cases), and furosemide (301 cases). Strong statistical correlation for signals was observed for vildagliptin [PRR = 295.8, LB (lower bound) ROR = 287.2, IC₀₂₅ = 7.5], dapsone [PRR = 20.7, LBROR = 14.4, IC₀₂₅ = 3.4], furosemide [PRR = 7.2, LBROR = 6.4, IC₀₂₅ = 2.6], and nivolumab [PRR = 31.5, LBROR = 28.5, IC₀₂₅ = 4.6]. These findings were supported by 106 identified case reports of BP.

Conclusion: This study suggests a strong statistical correlation between vildagliptin, dapsone, furosemide, nivolumab, and the development of BP.

Keywords: Antidiabetic agents; antimicrobial agents; biological agents; bullous pemphigoid; disproportionality analysis; diuretics; immune checkpoint inhibitors.