Association of Biliary Disorders with Immune Checkpoint Inhibitors: A
pharmacovigilance study
Abstract
Background: Immune checkpoint inhibitors (ICIs), including anti-PD-1/L1
therapy and anti-CTLA-4 therapy, are associated with a unique spectrum
of immune-related adverse events (irAEs). The association and clinical
features of ICIs-related biliary disorders are not well characterized.
Methods: Data were extracted from the US Food and Drug Administration
Adverse Event Reporting System (FAERS) database. Bile duct and
gallbladder diseases were defined by the Medical Dictionary for
Regulatory Activities (MedDRA). We performed disproportionality analysis
using reporting odds ratios (ROR) and information component (IC). The
result was defined as a signal if the lower limit of the 95% confidence
interval for ROR is over 1 and the number of cases ≥5, or the lower
limit of 95% confidence interval for the IC (IC025)>0.
Results: 906 reports of ICI-related bile duct and gallbladder events
were identified. The mean age was 64.8±12.1 years and the AEs occurred
more in men (60.1% vs 39.9%). ICIs were associated with increased
reporting of bile duct diseases (ROR 3.35, 95%CI 3.07-3.66; IC0251.41),
especially cholangitis (ROR 5.52, 95% CI 4.94-6.17; IC0251.93); while
we didn’t identify signal of gallbladder disease (ROR 0.96, 95%CI
0.86-1.08; IC025 -0.22). PD-1/L1 inhibitors and combination regimen were
associated with a spectrum of distinct classes of bile duct disease
while anti-CTLA-4 therapy (ipilimumab) had no association with any bile
duct and gallbladder diseases. Conclusions: PD-1/L1 inhibitors showed
increased reporting of cholangiopathy, especially for cholangitis.
Physicians should be aware of this potential adverse event.