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.