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 5·9 μg mL (−1) (ρ = –0·357, P = 0·032). Ustekinumab concentrations were higher in optimal responders (PASI ≤ 2) than in suboptimal responders (PASI > 2) (4·0 vs 2·8 μg mL (−1), P = 0·036). The ustekinumab concentration threshold associated with optimal response was determined to be 3·6 μg mL (−1) (area under the curve 0·71, 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 = 0·003 and P = 0·048, 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. What's already known about this topic? Monitoring drug concentrations is a valuable tool that can guide clinical decision‐making when drug concentrations are linked to clinical outcomes. The presence of a concentration–response relationship for ustekinumab at trough is still debated owing to the contradictory results reported. What does this study add? A concentration–response relationship at week 4 after injection for ustekinumab‐treated patients with psoriasis was demonstrated. Monitoring 4‐week postinjection ustekinumab concentrations could timely identify underexposed patients who might benefit from treatment optimization. Based on the findings of this study, a treatment algorithm for patients with a suboptimal response is proposed.