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.

We developed a mathematical model that describes systems-level AD pathogenesis involving dynamic interactions between S. aureus and Coagulase Negative Staphylococcus (CoNS). Our model simulation reproduced the clinically observed detrimental effects of application of S. hominis A9 (ShA9) and flucloxacillin 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 log10 CFU/cm2, 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.

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.