Association of Serum Ustekinumab Levels With Clinical Response in Psoriasis

Abstract

Importance: High-cost biologic therapies have transformed the management of immune-mediated inflammatory diseases. To optimize outcomes and reduce costs, dose adjustment informed by measurement of circulating drug levels has been shown to be effective in various settings. However, limited evidence exists for this approach with the interleukin 12 and interleukin 23 inhibitor ustekinumab.

Objective: To evaluate clinical utility of therapeutic drug monitoring for ustekinumab in patients with psoriasis.

Design, setting, and participants: A prospective observational cohort of 491 adults with psoriasis was recruited to the multicenter Biomarkers of Systemic Treatment Outcomes in Psoriasis study within the British Association of Dermatologists Biologic and Immunomodulators Register from June 2009 to December 2017; samples from some patients were taken between 2009 and 2011 as part of a pilot study with the same inclusion criteria.

Exposure: Serum ustekinumab level measured at any point during the dosing cycle using an enzyme-linked immunosorbent assay.

Main outcomes and measures: Disease activity measured using the Psoriasis Area and Severity Index (PASI) score. Treatment response outcomes were PASI75 (75% reduction in PASI score from baseline [primary outcome]), PASI90 (90% reduction of PASI score from baseline), and absolute PASI score of 1.5 or less.

Results: A total of 491 patients (171 women and 320 men; mean [SD] age, 45.7 [12.8] years) had 1 or more serum samples (total, 853 samples obtained 0-56 weeks from start of treatment) and 1 or more PASI scores within the first year of treatment. Antidrug antibodies were detected in only 17 of 490 patients (3.5%). Early measured drug levels (1-12 weeks after starting treatment) were associated with PASI75 response 6 months after starting treatment (odds ratio, 1.38; 95% CI, 1.11-1.71) when adjusted for baseline PASI score, age, and ustekinumab dose. However, this finding was not consistent across the other PASI outcomes (PASI90 and PASI score of ≤1.5).

Conclusions and relevance: This real-world study provides evidence that measurement of early serum ustekinumab levels could be useful to direct the treatment strategy for psoriasis. Adequate drug exposure early in the treatment cycle may be particularly important in determining clinical outcome.

Figure 1.. Flow Diagram of Patients Included in the Study

PASI indicates Psoriasis Area and Severity Index.

Figure 2.. Box Plots Comparing Early Measured Drug Levels by Achievement of 75% Reduction From Baseline in Psoriasis Area and Severity Index at 6 Months

A, Split by response only. The nonresponse group contains 46 samples and the response group contains 73 samples. B, Split by response and by ustekinumab dose. The nonresponse group receiving 45 mg of ustekinumab contains 18 samples, the response group receiving 45 mg of ustekinumab contains 50 samples, the nonresponse group receiving 90 mg of ustekinumab contains 28 samples, and the response group receiving 90 mg of ustekinumab contains 23 samples. In both panels, the middle line is the median, white circles are the means, ends of boxes are the lower and upper quartiles, dark blue circles are outliers (values ≥1.5 times the interquartile range from the lower and upper quartiles), and whiskers show the minimum and maximum values (unless there are outliers, in which case they are 1.5 times the interquartile range from the lower and upper quartiles).

Figure 3.. Probability of Achieving 75% Reduction From Baseline in Psoriasis Area and Severity Index Score at 6 Months Based on Early Measured Drug Level, Split by Ustekinumab Dose

Probability of response is split by ustekinumab dose. Solid lines plot the marginal predicted probability of response; the shaded areas indicate 95% CIs.