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• W3203071511 abstract "ABSTRACT Background Several clinical trials of Staphylococcus aureus ( S. aureus )-targeted therapies for atopic dermatitis (AD) have demonstrated conflicting results regarding whether they improve AD severity scores. This study performs a model-based meta-analysis to investigate possible causes of these conflicting results and suggests how to improve the efficacies of S. aureus -targeted therapies. Methods We developed a mathematical model that describes systems-level AD pathogenesis involving interactions between S. aureus and Coagulase Negative Staphylococcus (CoNS). The model was calibrated to reproduce time course data of S. aureus levels, EASI scores, and EASI-75 in response to dupilumab, S. hominis A9 ( Sh A9) and flucloxacillin from published clinical trials. We simulated efficacies of hypothetical S. aureus -targeted therapies on virtual patients using the model. Results Our model simulation reproduced the clinically observed detrimental effects that application of Sh A9 and flucloxacillin had on AD severity and showed that these effects disappeared if the bactericidal activity against CoNS was removed. A hypothetical (modelled) eradication of S. aureus by 3.0 log 10 CFU/cm 2 , without killing CoNS, achieved comparable EASI-75 to dupilumab. This efficacy was potentiated if dupilumab was administered in conjunction with S. aureus eradication (EASI-75 at week 16; S. aureus eradication: 66.7%, dupilumab 61.6% and combination: 87.8%). The improved efficacy was also seen for virtual dupilumab poor responders. Conclusion Our model simulation suggests that killing CoNS worsens AD severity and that S. aureus -specific eradication without killing CoNS could be effective for AD patients, including dupilumab poor responders. This study will contribute to design promising S. aureus -targeted therapy." @default.
• W3203071511 created "2021-10-11" @default.
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• W3203071511 date "2021-10-07" @default.
• W3203071511 modified "2023-10-16" @default.
• W3203071511 title "Model-based meta-analysis to optimise S. aureus-targeted therapies for atopic dermatitis" @default.
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• W3203071511 doi "https://doi.org/10.1101/2021.10.04.21264531" @default.
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