ustekinumab a human immunoglobulin g1 kappa igg1k monoclonal antibody that binds with high affinity to human interleukin 12 and interleukin 23 has demonstrated efficacy in patients with psoriasis the objective of this study was to perform exposure response modeling to increase the understanding of reduction in disease severity following treatment with ustekinumab in patients with moderate to severe psoriasis who participate in two phase iii studies phoenix 1 and phoenix 2 patients were randomly assigned to receive ustekinumab 45 mg or 90 mg n 1312 11 624 psoriasis area and severity index pasi scores or placebo n 665 3278 pasi scores disease severity was assessed using pasi scores a population mechanism based exposure response model of ustekinumab using nonmem was developed using serum ustekinumab concentrations and pasi scores the pharmacodynamic response effect was the reduction in pasi score the placebo effect although minor was also integrated into the model none of the covariate factors evaluated eg demographics baseline disease characteristics comorbidities significantly contributed to the between subject variability in the pharmacodynamic parameters the developed exposure response model can serve as a basis to support future alternative dosing regimens for ustekinumab in patients with moderate to severe plaque psoriasis a robust exposure response relationship has been confirmed for ustekinumab in psoriasis.