Association of Serum Ustekinumab Levels With Clinical Response in Psoriasis

Abstract

; for the British Association of Dermatologists Biologic and Immunomodulators Register (BADBIR) Study Group and the Psoriasis Stratification to Optimise Relevant Therapy (PSORT) Consortium 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 Յ1.5). 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.

Using Real‐World Data to Guide Ustekinumab Dosing Strategies for Psoriasis: A Prospective Pharmacokinetic‐Pharmacodynamic Study

“…and Zhou et al ., we maximized clinical relevance by including covariates already known to affect response to biologics across the BADBIR cohort. As reported elsewhere, we also confirm in our real‐world cohort that ustekinumab has relatively low immunogenicity in the setting of clinical practice, with only 3.3% of patients developing detectable ADA …”

“…As reported elsewhere, we also confirm in our real-world cohort that ustekinumab has relatively low immunogenicity in the setting of clinical practice, with only 3.3% of patients developing detectable ADA. 23 Our study had some limitations. As with any real-world cohort, a key issue is missing data.…”

“…Psoriasis represents an ideal disease model to investigate the utility of TDM, because treatment response is visually observed and easily quantifiable over time. Here, we use a large‐scale real‐world data set from the multicenter cohort study Biomarkers of Systemic Treatment Outcomes in Psoriasis (BSTOP), within the UK pharmacovigilance registry British Association of Dermatologists Biologics and Immunomodulators Registry (BADBIR).…”

Drug survival of adalimumab, ustekinumab and secukinumab in patients with psoriasis: a prospective cohort study from the British Association of Dermatologists Biologics and Immunomodulators Register (BADBIR)

“…Similarly to our previous work to develop a model using clinical baseline factors to predict serious infection in patients starting biologic therapies, clinical factors appear to be poorly predictive of drug discontinuation due to ineffectiveness. Work by the Psoriasis Stratification to Optimise Relevant Therapy (PSORT) consortium in the UK has identified that pharmacokinetic factors such as early drug levels are important for prediction of later treatment response for adalimumab and ustekinumab, and it may be that the determinants of biologic pharmacokinetics such as propensity to develop antidrug antibodies or other factors affecting distribution and bioavailability of biologic therapies are more predictive of drug ineffectiveness than are clinical covariates. In addition, there may be other unmeasured factors that might be predictive of biologic ineffectiveness, such as genomic and transcriptomic data, and drug adherence.…”

The Management of Erythrodermic Psoriasis Complicated by Cyclosporine

“…Other alternative therapies such as acitretin and methotrexate are less studied but are known to have a slower onset of action. Adalimumab and ustekinumab have also been useful in treating patients with moderate to severe plaque psoriasis [ 10 ].…”