Drug-associated infections and infestations in older adults with tumor necrosis factor-alpha inhibitors: a real-world retrospective and pharmacovigilance study

ObjectiveOne of the adverse events of greatest concern in patients receiving biologic therapies is the risk of infection, as infections are among the primary causes of premature mortality in this population, especially in the elderly. Because of the absence of head-to-head studies and limited durati...

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Main Authors: Xihui Yu, Jiahong Zhong, Xuemei Zhuang, Zhuomiao Lin, Hongbo Fu, Yaofeng Zhang
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-04-01
Series:Frontiers in Pharmacology
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Online Access:https://www.frontiersin.org/articles/10.3389/fphar.2025.1533902/full
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author Xihui Yu
Jiahong Zhong
Xuemei Zhuang
Zhuomiao Lin
Hongbo Fu
Yaofeng Zhang
author_facet Xihui Yu
Jiahong Zhong
Xuemei Zhuang
Zhuomiao Lin
Hongbo Fu
Yaofeng Zhang
author_sort Xihui Yu
collection DOAJ
description ObjectiveOne of the adverse events of greatest concern in patients receiving biologic therapies is the risk of infection, as infections are among the primary causes of premature mortality in this population, especially in the elderly. Because of the absence of head-to-head studies and limited duration and sample size of randomized controlled trials in the older adults, we analyzed the risk of infection associated with tumor necrosis factor (TNF) inhibitors by real-world adverse event analysis, seeking to identify medications with a reduced risk of infection and offering medication options for sensitive patients.MethodsA retrospective pharmacovigilance investigation was undertaken utilizing the FDA Adverse Event Reporting System (FAERS) database from the first quarter of 2010 to the fourth quarter of 2023. Drug-associated infections and infestations associated with TNF-α inhibitors (adalimumab, infliximab, etanercept, golimumab, and certolizumab pegol) were evaluated using a disproportionality analysis. The Reporting Odds Ratio (ROR) and Bayesian Confidence Propagation Neural Network (BCPNN) were utilized to detect AE signals.ResultsA total case of 3,239,508 cases were included after removing duplicates. Among the protective signals, etanercept showed the lowest IC025 value in septic shock (IC025 = −3.23). Notably, golimumab showed the highest IC025 value in tuberculosis (IC025 = 2.44). The five TNF-α inhibitors have high signals in mycobacterial infectious disorders. In the stratification analysis, golimumab was associated with a highest risk of infections and infestations in ankylosing spondylitis patients (ROR = 3.07, 95%CI = 2.70–3.50; IC = 1.26, 95%CI = −0.42–2.92). Univariate and multivariate logistic regression analysis indicated that gender, weight and medicine may be influencing factors for the AEs of infections and infestations (p < 0.05).ConclusionThe research highlighted that the difference in the risk of infection in the elderly who used TNF-α inhibitors between various TNF-α inhibitors, adverse events and therapeutic indications, respectively. The use of TNF-α inhibitors increased the infection risk in older adults. Etanercept exhibited the lowest infection risk, whereas certolizumab pegol manifested the highest risk in infections and infestations. Doctors need to pay close attention to the appearance of mycobacterial infectious disorders in older adults treating with TNF-α inhibitors, which displayed the strongest signal.
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spelling doaj-art-d6564ef045d7412d8541e4531dca36352025-08-20T03:53:39ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122025-04-011610.3389/fphar.2025.15339021533902Drug-associated infections and infestations in older adults with tumor necrosis factor-alpha inhibitors: a real-world retrospective and pharmacovigilance studyXihui Yu0Jiahong Zhong1Xuemei Zhuang2Zhuomiao Lin3Hongbo Fu4Yaofeng Zhang5Department of Pharmacy, The Second Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, ChinaDepartment of Clinical Pharmacy, Meizhou People’s Hospital (Huangtang Hospital), Meizhou, Guangdong, ChinaDepartment of Pharmacy, Qingdao Central Hospital, University of Health and Rehabilitation Sciences, Qingdao, Shandong, ChinaDepartment of Clinical Pharmacy, Meizhou People’s Hospital (Huangtang Hospital), Meizhou, Guangdong, ChinaDepartment of Pharmacy, The Second Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, ChinaDepartment of Pharmacy, The Second Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, ChinaObjectiveOne of the adverse events of greatest concern in patients receiving biologic therapies is the risk of infection, as infections are among the primary causes of premature mortality in this population, especially in the elderly. Because of the absence of head-to-head studies and limited duration and sample size of randomized controlled trials in the older adults, we analyzed the risk of infection associated with tumor necrosis factor (TNF) inhibitors by real-world adverse event analysis, seeking to identify medications with a reduced risk of infection and offering medication options for sensitive patients.MethodsA retrospective pharmacovigilance investigation was undertaken utilizing the FDA Adverse Event Reporting System (FAERS) database from the first quarter of 2010 to the fourth quarter of 2023. Drug-associated infections and infestations associated with TNF-α inhibitors (adalimumab, infliximab, etanercept, golimumab, and certolizumab pegol) were evaluated using a disproportionality analysis. The Reporting Odds Ratio (ROR) and Bayesian Confidence Propagation Neural Network (BCPNN) were utilized to detect AE signals.ResultsA total case of 3,239,508 cases were included after removing duplicates. Among the protective signals, etanercept showed the lowest IC025 value in septic shock (IC025 = −3.23). Notably, golimumab showed the highest IC025 value in tuberculosis (IC025 = 2.44). The five TNF-α inhibitors have high signals in mycobacterial infectious disorders. In the stratification analysis, golimumab was associated with a highest risk of infections and infestations in ankylosing spondylitis patients (ROR = 3.07, 95%CI = 2.70–3.50; IC = 1.26, 95%CI = −0.42–2.92). Univariate and multivariate logistic regression analysis indicated that gender, weight and medicine may be influencing factors for the AEs of infections and infestations (p < 0.05).ConclusionThe research highlighted that the difference in the risk of infection in the elderly who used TNF-α inhibitors between various TNF-α inhibitors, adverse events and therapeutic indications, respectively. The use of TNF-α inhibitors increased the infection risk in older adults. Etanercept exhibited the lowest infection risk, whereas certolizumab pegol manifested the highest risk in infections and infestations. Doctors need to pay close attention to the appearance of mycobacterial infectious disorders in older adults treating with TNF-α inhibitors, which displayed the strongest signal.https://www.frontiersin.org/articles/10.3389/fphar.2025.1533902/fullTNF-α inhibitorimmune-mediated inflammatory diseasesFAERSolder adultsinfectioninfestation
spellingShingle Xihui Yu
Jiahong Zhong
Xuemei Zhuang
Zhuomiao Lin
Hongbo Fu
Yaofeng Zhang
Drug-associated infections and infestations in older adults with tumor necrosis factor-alpha inhibitors: a real-world retrospective and pharmacovigilance study
Frontiers in Pharmacology
TNF-α inhibitor
immune-mediated inflammatory diseases
FAERS
older adults
infection
infestation
title Drug-associated infections and infestations in older adults with tumor necrosis factor-alpha inhibitors: a real-world retrospective and pharmacovigilance study
title_full Drug-associated infections and infestations in older adults with tumor necrosis factor-alpha inhibitors: a real-world retrospective and pharmacovigilance study
title_fullStr Drug-associated infections and infestations in older adults with tumor necrosis factor-alpha inhibitors: a real-world retrospective and pharmacovigilance study
title_full_unstemmed Drug-associated infections and infestations in older adults with tumor necrosis factor-alpha inhibitors: a real-world retrospective and pharmacovigilance study
title_short Drug-associated infections and infestations in older adults with tumor necrosis factor-alpha inhibitors: a real-world retrospective and pharmacovigilance study
title_sort drug associated infections and infestations in older adults with tumor necrosis factor alpha inhibitors a real world retrospective and pharmacovigilance study
topic TNF-α inhibitor
immune-mediated inflammatory diseases
FAERS
older adults
infection
infestation
url https://www.frontiersin.org/articles/10.3389/fphar.2025.1533902/full
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