Conducting a real-world study of Tumor Necrosis factor-alpha inhibitors-induced Systemic Lupus Erythematosus based on the FAERS database

Abstract This study characterized the risk and characteristics of tumor necrosis factor-α (TNF-α) inhibitors-induced systemic lupus erythematosus (SLE) in a mass medication population based on the FAERS database. Using the Standardized MedDRA Query (SMQ), adverse drug reaction (ADR) reports related...

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Main Authors: Mengjiao He, Jiale Yang, Simin Yan, Qing Shu, Peng Cheng Liu
Format: Article
Language:English
Published: Nature Portfolio 2025-02-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-90566-3
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author Mengjiao He
Jiale Yang
Simin Yan
Qing Shu
Peng Cheng Liu
author_facet Mengjiao He
Jiale Yang
Simin Yan
Qing Shu
Peng Cheng Liu
author_sort Mengjiao He
collection DOAJ
description Abstract This study characterized the risk and characteristics of tumor necrosis factor-α (TNF-α) inhibitors-induced systemic lupus erythematosus (SLE) in a mass medication population based on the FAERS database. Using the Standardized MedDRA Query (SMQ), adverse drug reaction (ADR) reports related to SLE of infliximab, adalimumab, etanercept, golimumab, and certolizumab pegol were collected from the FAERS database starting from the data retrieval quarter up to the fourth quarter of 2023. Signal detection was performed using the Reporting Odds Ratio (ROR) method and the Bayesian Confidence Interval Propagation Neural Network (BCPNN) method to comprehensively explore the risks. Subgroup analyses were conducted for different genders and age groups to provide a detailed insight into the risks. A total of 12,080 reports of TNF-α inhibitors-induced SLE have been collected, with over 90% of the reports showing serious outcomes, including life-threatening, death and others. Notably, deaths were prominently associated with certolizumab pegol and etanercept. Regarding time to onset, the median time to onset after drug use was over 7 months for infliximab, adalimumab, and etanercept, while for golimumab and certolizumab pegol, the median time to onset was around 2 months post-treatment. At the SMQ level, all five TNF-α inhibitors showed statistically significant signals in the overall population, with the strength of association ranked as infliximab > adalimumab > certolizumab pegol > golimumab > etanercept. In terms of PT level, apart from signals related to lupus-like syndrome, systemic lupus erythematosus, and systemic lupus erythematosus rash, notable findings include the higher signal intensity of SLE arthritis in the subgroup of male with adalimumab, lupus nephritis risk associated with etanercept in the children (0–14 years) subgroup, and rare and severe occurrences of pericarditis lupus and lupus pleurisy induced by infliximab. This study utilized large-scale real-world data to reveal varying degrees of SLE associated with five TNF-α inhibitors and characterized specific risk signals of concern across gender and age subgroups. This suggests that different TNF-α inhibitors should be continuously monitored for SLE-induced complications in clinical practice, and that appropriate drug management should be carried out for different patients. Further research is necessary to validate our findings.
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spelling doaj-art-53ff141fee2f4726830ec73bcdb285b22025-08-20T02:59:35ZengNature PortfolioScientific Reports2045-23222025-02-0115111410.1038/s41598-025-90566-3Conducting a real-world study of Tumor Necrosis factor-alpha inhibitors-induced Systemic Lupus Erythematosus based on the FAERS databaseMengjiao He0Jiale Yang1Simin Yan2Qing Shu3Peng Cheng Liu4School of International Pharmaceutical Business, China Pharmaceutical UniversitySchool of International Pharmaceutical Business, China Pharmaceutical UniversityDepartment of Pharmacy, Naijing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing UnversityDepartment of Pharmacy, Naijing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing UnversitySchool of International Pharmaceutical Business, China Pharmaceutical UniversityAbstract This study characterized the risk and characteristics of tumor necrosis factor-α (TNF-α) inhibitors-induced systemic lupus erythematosus (SLE) in a mass medication population based on the FAERS database. Using the Standardized MedDRA Query (SMQ), adverse drug reaction (ADR) reports related to SLE of infliximab, adalimumab, etanercept, golimumab, and certolizumab pegol were collected from the FAERS database starting from the data retrieval quarter up to the fourth quarter of 2023. Signal detection was performed using the Reporting Odds Ratio (ROR) method and the Bayesian Confidence Interval Propagation Neural Network (BCPNN) method to comprehensively explore the risks. Subgroup analyses were conducted for different genders and age groups to provide a detailed insight into the risks. A total of 12,080 reports of TNF-α inhibitors-induced SLE have been collected, with over 90% of the reports showing serious outcomes, including life-threatening, death and others. Notably, deaths were prominently associated with certolizumab pegol and etanercept. Regarding time to onset, the median time to onset after drug use was over 7 months for infliximab, adalimumab, and etanercept, while for golimumab and certolizumab pegol, the median time to onset was around 2 months post-treatment. At the SMQ level, all five TNF-α inhibitors showed statistically significant signals in the overall population, with the strength of association ranked as infliximab > adalimumab > certolizumab pegol > golimumab > etanercept. In terms of PT level, apart from signals related to lupus-like syndrome, systemic lupus erythematosus, and systemic lupus erythematosus rash, notable findings include the higher signal intensity of SLE arthritis in the subgroup of male with adalimumab, lupus nephritis risk associated with etanercept in the children (0–14 years) subgroup, and rare and severe occurrences of pericarditis lupus and lupus pleurisy induced by infliximab. This study utilized large-scale real-world data to reveal varying degrees of SLE associated with five TNF-α inhibitors and characterized specific risk signals of concern across gender and age subgroups. This suggests that different TNF-α inhibitors should be continuously monitored for SLE-induced complications in clinical practice, and that appropriate drug management should be carried out for different patients. Further research is necessary to validate our findings.https://doi.org/10.1038/s41598-025-90566-3Systemic lupus erythematosusFAERS databaseDisproportionality analysis;Pharmacovigilance
spellingShingle Mengjiao He
Jiale Yang
Simin Yan
Qing Shu
Peng Cheng Liu
Conducting a real-world study of Tumor Necrosis factor-alpha inhibitors-induced Systemic Lupus Erythematosus based on the FAERS database
Scientific Reports
Systemic lupus erythematosus
FAERS database
Disproportionality analysis;
Pharmacovigilance
title Conducting a real-world study of Tumor Necrosis factor-alpha inhibitors-induced Systemic Lupus Erythematosus based on the FAERS database
title_full Conducting a real-world study of Tumor Necrosis factor-alpha inhibitors-induced Systemic Lupus Erythematosus based on the FAERS database
title_fullStr Conducting a real-world study of Tumor Necrosis factor-alpha inhibitors-induced Systemic Lupus Erythematosus based on the FAERS database
title_full_unstemmed Conducting a real-world study of Tumor Necrosis factor-alpha inhibitors-induced Systemic Lupus Erythematosus based on the FAERS database
title_short Conducting a real-world study of Tumor Necrosis factor-alpha inhibitors-induced Systemic Lupus Erythematosus based on the FAERS database
title_sort conducting a real world study of tumor necrosis factor alpha inhibitors induced systemic lupus erythematosus based on the faers database
topic Systemic lupus erythematosus
FAERS database
Disproportionality analysis;
Pharmacovigilance
url https://doi.org/10.1038/s41598-025-90566-3
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