# Refined pharmacovigilance assessment of immune checkpoint inhibitors-related bullous pemphigoid: a multi-methodological approach utilizing FAERS database

## TL;DR

This study uses multiple methods to show that immune checkpoint inhibitors increase the risk of bullous pemphigoid, a skin condition, with some drugs causing it earlier than others.

## Contribution

A multi-methodological approach to assess and characterize the risk of bullous pemphigoid associated with immune checkpoint inhibitors using FAERS data.

## Key findings

- All eight immune checkpoint inhibitors showed a significant increased risk of bullous pemphigoid.
- CTLA-4 inhibitors like ipilimumab showed the most marked early risk of bullous pemphigoid onset.
- The median time to onset of bullous pemphigoid was 165.2 days after starting treatment.

## Abstract

To evaluate the potential risk of bullous pemphigoid (BP) in patients treated with immune checkpoint inhibitors (ICIs) and to characterize ICI-related BP (irBP) using the United States Food and Drug Administration Adverse Event Reporting System (FAERS) database.

The present study conducted a disproportionality analysis leveraging FAERS database, spanning the first quarter (Q1) of 2004–2025 Q1. To ensure robust signal detection, we employed a quadruple analytical approach incorporating: (1) reporting odds ratio (ROR), (2) proportional reporting ratio, (3) Bayesian confidence propagation neural network, and (4) multi-item gamma Poisson shrinker algorithms. These methodologies were systematically applied to assess the potential risk of BP in patients treated with ICIs. Furthermore, temporal characteristics of adverse event emergence were quantitatively assessed to delineate the time-to-onset patterns.

There are 850 irBP cases identified, comprising reports associated with the following agents: nivolumab (n = 530), pembrolizumab (n = 180), ipilimumab (n = 44), atezolizumab (n = 40), cemiplimab (n = 24), durvalumab (n = 19), tislelizumab (n = 10), and avelumab (n = 3). Affected patients were predominantly males (67.8%) and over 60 years of age (70.1%). All eight ICIs showed positive disproportionality signals, with ROR values ranked descendingly as: cemiplimab > nivolumab > tislelizumab > pembrolizumab > ipilimumab > durvalumab > atezolizumab > avelumab. The median time of irBP onset was 165.2 (IQR: 56–410) days.

The study establishes a significant link between ICIs and BP. All ICIs increase BP risk. CTLA-4 inhibitors exhibited the most marked early risk concentration, highlighting the importance of early dermatologic evaluation after initiating CTLA-4 blockade.