Concentrations of Ustekinumab During Induction Therapy Associate With Remission in Patients With Crohn’s Disease

Soufflet, N; Boschetti, Gilles; Roblin, Xavier; Cuercq, Charlotte; Williet, Nicolas; Charlois, Anne-Laure; Duclaux-Loras, Rémi; Danion, Pauline; Mialon, A.; Faure, Mathias; Paul, Stéphane; Flourié, Bernard; Nancey, Stéphane

doi:10.1016/j.cgh.2019.02.042

Cited by 42 publications

(37 citation statements)

References 8 publications

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“…A threshold of 2 mg/l for cUSTw8 was associated with higher rates of clinical response at a later time point in the course of the treatment. Our results are consistent with recent findings from Soufflet and colleagues [5], who analyzed cUSTw8 using an enzyme linked immunosorbent assay (ELISA) in a smaller patient sample with a similar approach, indicating cUSTw8 of 2 mg/l or higher to be associated with clinical response. Earlier studies reported concentrations of up to 4.5 mg/l in week 26 to be associated with endoscopic response and biomarker reduction [4,9].…”

Section: Discussionsupporting

confidence: 92%

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Ustekinumab serum concentrations are associated with clinical outcomes in Crohn’s disease – a regional multi-center pilot study

et al. 2020

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Background and aim The role of therapeutic drug monitoring (TDM) in ustekinumab (UST) therapy for Crohn’s disease (CD) has not been established, as only few studies have analyzed the relationship between UST serum concentrations and clinical outcome. In this pilot study, we retrospectively examined the potential of UST-concentrations (cUST) 8 weeks after induction (cUSTw8) to predict clinical response at week 16. Methods Serum samples and clinical data from patients (n = 72) with moderate to severely active CD who received intravenous induction with UST were retrospectively analyzed. cUST were quantitated using liquid chromatography-tandem mass spectrometry (LC-MSMS). A receiver-operating characteristic (ROC) curve and area under ROC curve (AUROC) was computed to analyze the predictive potential of cUSTw8 for clinical response at week 16 and to determine the minimal therapeutic UST trough concentration. Results Forty-four patients (61 %) achieved clinical response to UST therapy at week 16. cUSTw8 was moderately effective to predict clinical response with a minimal therapeutic cUSTw8 of 2.0 mg/l (AUC 0.72, p = 0.001). Conclusion Trough concentrations of UST 8 weeks after induction predict clinical response to therapy in week 16 with moderate sensitivity and specificity. TDM using LC-MSMS could prove beneficial in personalized UST therapy of patients with CD by identifying individuals with subtherapeutic concentrations who might benefit from dose escalation.

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Section: Discussionsupporting

confidence: 92%

“…For UST therapy, the value of TDM has not been firmly established yet, as only a few studies have examined UST concentrations (cUST) and their association with clinical outcomes [4,5].…”

Section: Introductionmentioning

confidence: 99%

Ustekinumab serum concentrations are associated with clinical outcomes in Crohn’s disease – a regional multi-center pilot study

et al. 2020

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“…Although minor discrepancies in outcome definitions preclude a direct comparison, the predictive value of ustekinumab concentrations measured up to week 2 was at least as good, if not better, than that of concentrations measured at weeks 4 and 8 in two previous studies. 8,10 The identified cut-off values at later time points in our study were in the range of those identified in previous studies, which further supports the validity of our results.…”

Section: Discussionsupporting

confidence: 91%

“…This study is the first with a prospective real-world design to explore the correlation between very early ustekinumab exposure (within 2 weeks of starting treatment) and endoscopic and biochemical outcomes. We confirmed the predictive value of week 4 and 8 drug concentrations identified in previous studies [8][9][10] for biochemical and endoscopic remission after 6 months of treatment.…”

Section: Discussionsupporting

confidence: 90%

“…[6][7][8] Recently, an association of ustekinumab concentrations at weeks 4 and later with treatment outcomes has been observed in trials and real-world cohorts. [8][9][10] However, the exposure-response relationship at even earlier time points, during the first 2 weeks of treatment, is unclear. Since future optimization protocols (e.g., STARDUST -NCT03107793) include early shortening of the dosing interval to 4 weeks, the identification of patients needing this dosing regimen at an earlier time point than currently studied, i.e., during the first 2 weeks after starting treatment, rather than at weeks 4 or 8, would be clinically informative.…”

Section: Introductionmentioning

confidence: 99%

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Peak Concentrations of Ustekinumab After Intravenous Induction Therapy Identify Patients With Crohn’s Disease Likely to Achieve Endoscopic and Biochemical Remission

Hanžel

Zdovc

Kurent

et al. 2021

Clinical Gastroenterology and Hepatology

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Ustekinumab Trough Concentrations Are Associated with Biochemical Outcomes in Patients with Crohn’s Disease

et al. 2023

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Objective It is unknown whether ustekinumab (UST) levels can predict clinical outcomes in Crohn’s disease (CD) patients. We assessed the exposure–response relationship of UST trough concentrations with biochemical outcomes at week 24 in a prospective, real-world setting. Methods We performed a prospective study in patients with CD starting UST in four academic centres in the Netherlands. All patients received a weight-adjusted intravenous (IV) UST induction dose, followed by one subcutaneous (SC) dose of 90 mg UST at 8 weeks. Maintenance therapy consisted of 90 mg subcutaneous UST every 8 or 12 weeks. Individual UST concentration time course during treatment were estimated using a population pharmacokinetic (PK) model. Quartile analysis and logistic regression were performed to analyse if UST concentrations at week 8 were associated with biochemical remission rates at week 24 (C-reactive protein (CRP) ≤ 5 mg/L and / or faecal calprotectin (FC) ≤ 250 mg/kg). Results In total, 124 patients with CD were included. Patients achieving biochemical remission at week 12 and 24 had significantly higher UST levels at week 8 compared to patients without biochemical remission (6.6 µg/mL versus 3.9 µg/mL, P < 0.01 and 6.3 µg/mL versus 3.9 µg/mL, P < 0.01, respectively). In quartile analysis, patients with UST levels in the highest quartile (≥ 6.3 µg/mL at week 8) had higher biochemical remission rates at week 12 and week 24. There was no association between UST levels at and corticosteroid-free clinical remission rates. Conclusion In this real-world cohort of patients with CD, UST levels in the highest quartile (≥ 6.3 µg/mL) at week 8 were associated with higher biochemical remission rates at week 24. Supplementary Information The online version contains supplementary material available at 10.1007/s10620-023-07822-7.

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Concentrations of Ustekinumab During Induction Therapy Associate With Remission in Patients With Crohn’s Disease

Cited by 42 publications

References 8 publications

Ustekinumab serum concentrations are associated with clinical outcomes in Crohn’s disease – a regional multi-center pilot study

Ustekinumab serum concentrations are associated with clinical outcomes in Crohn’s disease – a regional multi-center pilot study

Peak Concentrations of Ustekinumab After Intravenous Induction Therapy Identify Patients With Crohn’s Disease Likely to Achieve Endoscopic and Biochemical Remission

Ustekinumab Trough Concentrations Are Associated with Biochemical Outcomes in Patients with Crohn’s Disease

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