Mining safety signals of PD-1/PD-L1 inhibitor-related adrenal insufficiency: a study based on the FAERS database

PurposeThis study evaluated the potential association between programmed cell death protein-1/ligand-1 (PD-1/PD-L1) inhibitors and adrenal insufficiency (AI) in the Food and Drug Administration Adverse Event Reporting System (FAERS) database to explore drug safety signals. MethodsThis study extracted real-world adverse event reports from the FAERS database spanning 2004 Q1 to 2024 Q4. Multiple disproportionality analysis methods were employed to evaluate the association between PD-1/PD-L1 inhibitors and AI, including the Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN) based on Information Component (IC), and Multi-item Gamma Poisson Shrinker (MGPS) methods. ResultsA total of 164,152 adverse events related to PD-1/PD-L1 inhibitors were identified in the FAERS database, among which 1,023 cases were associated with AI. The top three drugs with the highest signal strength, measured by IC₀₂₅, tislelizumab (IC₀₂₅ = 5.53), pembrolizumab (IC₀₂₅ = 4.01), and cemiplimab (IC₀₂₅ = 3.53). Time-to-onset analysis indicated that durvalumab and pembrolizumab were associated with the highest risk of AI during the initial treatment period (3-6 months), followed by a declining trend. Subgroup analysis showed a higher risk in patients over 65, males at significantly higher risk than females, and a stronger association of gastric cancer with AI risk signals than other cancers. Additionally, combination therapy with paclitaxel or lenvatinib mesylate was associated with an increased risk of AI onset.ConclusionsPD-1/PD-L1 inhibitors carry a potential risk of AI, and emphasis should be placed on early monitoring during clinical use to reduce the occurrence of adverse events.