Figure 5.

Hypothetical Staphylococcus aureus‒targeted therapies achieved better EASI-75 after 16 weeks of treatment than dupilumab in our model simulation. (a) Antimicrobial effects of hypothetical S. aureus‒targeted therapies are represented by the level of S. aureus, the level of CoNS, and the inhibition level of agr expression after 16 weeks of treatment. Hypothetical S. aureus‒targeted therapies were represented in our model by varying the strengths of S. aureus killing, CoNS killing, and inhibition of agr expression. (b, c) Antimicrobial effects of hypothetical S. aureus‒targeted therapies evaluated by EASI-75 after 16 weeks of treatment (b) for all virtual patients and (c) for virtual dupilumab poor responders. Lower S. aureus levels, higher CoNS levels, and stronger inhibition of agr expression achieved a better EASI-75. The hypothetical S. aureus‒specific eradication (yellow arrows) achieved (b) comparable or (c) better EASI-75 than dupilumab (dotted line in b and 0% in c), and its EASI-75 was potentiated (triangle) by adding 90% inhibition of agr expression (blue arrows). Their combination application with dupilumab achieved better EASI-75 than an application of either alone. The effects of dupilumab were modeled by inhibiting IL-4/IL-13 by 99%. The simulation was conducted on 1,000 virtual patients or 1,000 virtual dupilumab poor responders (levels of S. aureus and CoNS and the inhibition level of agr expression: shown as the mean values, EASI-75 denotes the responder rates). agr, accessory gene regulatory; CFU, colony-forming unit; CoNS, coagulase-negative Staphylococcus; EASI, Eczema Area and Severity Index.