Association between immune-mediated cystitis and PD-1,PD-L1,CTLA-4,and LAG-3 immune checkpoint inhibitors: A pharmacovigilance study from the FAERS database

Abstract

Background:

Immune checkpoint inhibitors (ICIs) have transformed oncology but predispose patients to immune-related adverse events. Immune-mediated cystitis represents a rare yet clinically significant urological complication requiring enhanced surveillance. This studies characterizes the pharmacovigilance profile of immune-mediated cystitis across ICI classes using real-world post-market surveillance data.

Patients and methods:

This disproportionality analysis utilized the FDA Adverse Event Reporting System (FAERS) database, encompassing reports from Q4 2003 through Q3 2025. Fourteen ICIs were evaluated across four mechanistic classes: PD-1 (n = 7), PD-L1 (n = 4), CTLA-4 (n = 2), and LAG-3 (n = 1) inhibitors.

Results:

Among 14,104,743 adverse event reports, 69 cases of immune-mediated cystitis were identified. PD-1 inhibitors demonstrated the strongest signals: pembrolizumab (ROR 241.59; 95% CI 149.40–390.68; n = 28), nivolumab (ROR 118.56; 95% CI 68.56–205.02; n = 17), toripalimab (ROR 454.65; n = 2), and tislelizumab (ROR 266.31; n = 3). Ipilimumab exhibited robust disproportionality (ROR 297.28; 95% CI 167.73–526.89; n = 15). PD-L1 inhibitors showed minimal signals with isolated cases.

Conclusion:

Immune-mediated cystitis demonstrates strongest association with PD-1 and CTLA-4 inhibitors, warranting enhanced clinical surveillance, prompt recognition, and evidence-based management protocols.