Clinical response correlates with 4-week postinjection ustekinumab concentrations in patients with moderate-to-severe psoriasis

Background Cost-effective use of biologicals is important. As drug concentrations have been linked to clinical outcomes, monitoring drug concentrations is a valuable tool to guide clinical decision-making. A concentration-response relationship for ustekinumab at trough is uncertain owing to the contradictory results reported. Objectives To investigate the relationship between 4-week postinjection ustekinumab concentrations and clinical response in patients with psoriasis. Methods Forty-nine patients with moderate-to-severe psoriasis treated with 45 mg or 90 mg ustekinumab every 12 weeks for >= 16 weeks were included. Ustekinumab serum concentrations and anti-ustekinumab antibodies were measured at week 4 after injection and disease severity was assessed by Psoriasis Area and Severity Index (PASI). Results At week 4 after injection, a significantly negative correlation was observed between ustekinumab concentrations and absolute PASI score up to 5 center dot 9 mu g mL(-1) (rho = -0 center dot 357, P = 0 center dot 032). Ustekinumab concentrations were higher in optimal responders (PASI <= 2) than in suboptimal responders (PASI > 2) (4 center dot 0 vs 2 center dot 8 mu g mL(-1), P = 0 center dot 036). The ustekinumab concentration threshold associated with optimal response was determined to be 3 center dot 6 mu g mL(-1) (area under the curve 0 center dot 71, sensitivity 86%, specificity 63%). Only one patient (2%) had anti-ustekinumab antibodies. Psoriatic arthritis was identified as an independent predictor of higher PASI scores and higher ustekinumab concentrations (P = 0 center dot 003 and P = 0 center dot 048, respectively). Conclusions A concentration-response relationship at week 4 after injection was observed for patients with psoriasis treated with ustekinumab. Monitoring 4-week postinjection ustekinumab concentrations could timely identify underexposed patients who might benefit from treatment optimization.