Clinical Consequences of Antibody Formation, Serum Concentrations, and HLA-Cw6 Status in Psoriasis Patients on Ustekinumab

Abstract

Background: Ustekinumab for the treatment of psoriasis is currently administered in a standard dosing regimen. However, some patients tend to benefit from alternative dosing regimens, a step toward personalized medicine.

Methods: To investigate the role of ustekinumab serum concentrations, anti-ustekinumab antibodies [AUA] and HLA-Cw6 status as tools for optimizing ustekinumab treatment, a multicenter prospective cohort study was conducted at an academic hospital with affiliated nonacademic hospitals in Belgium (cohort 1) and 2 academic hospitals in the Netherlands (cohort 2 and 3). Patients with plaque-type psoriasis were eligible if treated with ustekinumab for ≥16 weeks. Serum samples and Psoriasis Area and Severity Index scores were obtained at baseline, week 16, 28, 40, 52, and/or ≥64 of ustekinumab treatment.

Results: A total of 137 patients with 229 observations for serum concentrations and AUA and 61 observations for HLA-Cw6 status were included. Presence of AUA (prevalence of 8.7%) was significantly associated with a diminished clinical response (P = 0.032). The median ustekinumab trough concentration was 0.3 mcg/mL (<0.02-3.80). No differences in serum concentrations were observed between moderate to good responders and nonresponders (P = 0.948). Serum trough concentrations were not affected by methotrexate comedication. Prevalence of HLA-Cw6 positivity was 41% with no statistically significant difference in clinical response between HLA-Cw6-positive and HLA-Cw6-negative patients (P = 0.164).

Conclusions: The presence of AUA was associated with treatment failure in this patient population; measurement of AUA may therefore be a candidate marker for personalized pharmacotherapy. The clinical utility of ustekinumab serum trough concentrations or HLA-Cw6 status determination remains less clear. Further exploration on the potential of measuring ustekinumab serum concentrations and other biomarkers in predicting therapy outcomes should be encouraged.

FIGURE 1.

Box-and-whisker plot showing ustekinumab trough concentrations across response groups. No statistically significant difference in serum trough concentrations was found between nonresponders, moderate responders, and good responders (P = 0.948). The limits of the boxes represent the interquartile (IQ) range. The line in the boxes is the median. The whiskers extend from the upper and lower edge of the box to the highest and lowest values, which are no greater than 1.5 times the IQ range. The circles and asterisks indicate outliers (values between 1.5 and 3 times the IQ range) and extreme outliers (values more than 3 times the IQ range), respectively.

FIGURE 2.

Clinical response according to AUA status. A good response was significantly more frequent achieved in AUA-negative patients compared with AUA-positive patients (44.1% versus 22.2%, P = 0.032).

FIGURE 3.

Clinical response according to HLA-Cw6 status. There was no statistically significant difference in response between HLA-Cw6–positive and HLA-Cw6–negative patients (P = 0.164).