Characterisation of systemic lupus erythematosus associated with immune checkpoint inhibitors: a pharmacovigilance study using FAERS database

利用FAERS数据库对免疫检查点抑制剂相关系统性红斑狼疮进行特征分析:一项药物警戒研究

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Abstract

OBJECTIVES: SLE associated with immune checkpoint inhibitors (ICIs) is rare, and a comprehensive profile of ICI-induced SLE remains poorly characterised. This study aimed to explore the potential association between ICIs and SLE and characterise clinical features. METHODS: We extracted adverse event reports of patients with cancer with SLE from the FAERS (US Food and Drug Administration Adverse Event Reporting System) database (Q1 2011-Q4 2024). A disproportionality analysis was conducted using the reporting OR (ROR) and the information component, with adjusted ROR calculated via logistic regression to control for confounders. RESULTS: 146 066 ICI-related adverse events cases from patients with cancer were identified. Among these, 209 (median (IQR) age 63 (55.3-71.7) years; 106 (51%) female) cases of SLEs were reported. Our analysis detected significant positive signals for SLE associated with ICIs overall, particularly for anti-programmed cell death protein 1 (PD-1) and anti-programmed death-ligand 1 therapy. Eight positive signals of SLEs were identified, predominantly cutaneous lupus and SLE. The risk of ICI-related SLEs was significantly higher in females than in males. However, age and chemotherapy were not significant risk factors for the incidence of ICI-related SLEs. The risk was higher with anti-PD-1 therapy compared with other ICI therapies. Patients with lung cancer, melanoma or breast cancer appeared to be at higher risk. Most patients experienced serious outcomes, with a mortality rate of 4.31% (nine cases). CONCLUSION: This first pharmacovigilance study identified a significant association between ICI use and SLEs, suggesting ICIs may constitute a novel class of drug-induced SLE triggers. Personalised long-term safety monitoring for ICIs is warranted for high-risk patients (eg, females, anti-PD-1 recipients).

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