Usefulness and correlation with clinical response of serum ustekinumab levels measured at 6 weeks versus 12 weeks

Toro-Montecinos, M.; Ballescá, F.; Ferrándiz, Carlos; Teniente-Serra, Aina; Martı́nez-Cáceres, Eva; Carrascosa, José Manuel

doi:10.1080/09546634.2018.1468065

Cited by 13 publications

(14 citation statements)

References 11 publications

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“…Moreover, 4‐week postinjection ustekinumab concentrations were considerably higher in optimal responders than in suboptimal responders and 3·6 μg mL −1 was determined to be the ustekinumab concentration threshold associated with optimal response. In accordance with the findings of Toro‐Montecinos et al ., these results reveal the presence of a concentration–response relationship for ustekinumab at 4 weeks postinjection and demonstrate the usefulness of monitoring ustekinumab concentrations …”

Section: Discussionsupporting

confidence: 56%

“…To this day, owing to the contradictory results reported, no consensus has been reached regarding the presence of a concentration–response relationship for ustekinumab and the usefulness of monitoring ustekinumab concentrations. Two independent research groups did not observe a correlation between ustekinumab concentrations at trough and clinical response . In contrast, two other studies could distinguish responders from nonresponders based on the ustekinumab trough concentration; one Spanish group made a similar observation at 6 weeks postinjection .…”

Section: Discussionmentioning

confidence: 89%

“…Two independent research groups did not observe a correlation between ustekinumab concentrations at trough and clinical response . In contrast, two other studies could distinguish responders from nonresponders based on the ustekinumab trough concentration; one Spanish group made a similar observation at 6 weeks postinjection . For therapeutic drug monitoring of ustekinumab to be effective and implemented into clinical practice, physicians should know at which time point to measure ustekinumab concentrations and how to interpret the results.…”

Section: Discussionmentioning

confidence: 98%

“…Multiple studies have shown a correlation between serum trough – the drug concentration just before the next drug administration – and clinical response in adalimumab‐treated patients with psoriasis . However, for ustekinumab, the presence of a concentration–response relationship at trough is still debated owing to the contradictory results that have been reported . The mean ± SD steady‐state trough serum ustekinumab concentration is stated to be 0·69 ± 0·69 μg mL −1 and 0·74 ± 0·78 μg mL −1 for patients with psoriasis receiving 45 and 90 mg, respectively .…”

mentioning

confidence: 99%

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

et al. 2019

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Summary 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.

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Section: Discussionsupporting

confidence: 56%

Section: Discussionmentioning

confidence: 89%

Section: Discussionmentioning

confidence: 98%

mentioning

confidence: 99%

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

et al. 2019

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“…Initially developed for psoriasis (where it remains first‐line), it is now also licensed for use in psoriatic arthritis and inflammatory bowel disease . Studies investigating the relationship between ustekinumab exposure and outcome are few, generally limited to descriptive or empirical analyses, and report mixed results . Understanding exposure‐response is complicated by the fact that some patients’ disease may not respond to IL‐23‐Th17 therapies, and furthermore, some may receive subtherapeutic drug exposure due to PK variability.…”

mentioning

confidence: 99%

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

Pan

Dand

Lonsdale

et al. 2020

Clinical Translational Sci

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Variation in response to biologic therapy for inflammatory diseases, such as psoriasis, is partly driven by variation in drug exposure. Real‐world psoriasis data were used to develop a pharmacokinetic/pharmacodynamic (PK/PD) model for the first‐line therapeutic antibody ustekinumab. The impact of differing dosing strategies on response was explored. Data were collected from a UK prospective multicenter observational cohort (491 patients on ustekinumab monotherapy, drug levels, and anti‐drug antibody measurements on 797 serum samples, 1,590 measurements of Psoriasis Area Severity Index (PASI)). Ustekinumab PKs were described with a linear one‐compartment model. A maximum effect (Emax) model inhibited progression of psoriatic skin lesions in the turnover PD mechanism describing PASI evolution while on treatment. A mixture model on half‐maximal effective concentration identified a potential nonresponder group, with simulations suggesting that, in future, the model could be incorporated into a Bayesian therapeutic drug monitoring “dashboard” to individualize dosing and improve treatment outcomes.

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Association of Serum Ustekinumab Levels With Clinical Response in Psoriasis

et al. 2019

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; 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.

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Usefulness and correlation with clinical response of serum ustekinumab levels measured at 6 weeks versus 12 weeks

Abstract: Assessment of ustekinumab serum levels at week 6 could provide useful information in routine clinical practice.

Cited by 13 publications

References 11 publications

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

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

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

Association of Serum Ustekinumab Levels With Clinical Response in Psoriasis

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