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

Autor: Straatmijer T; Department of Gastroenterology and Hepatology, Leiden University Medical Centre, Albinusdreef 2, 2333 ZA, Leiden, The Netherlands.; Division Gastroenterology-Hepatology, Maastricht University Medical Center+, Maastricht, The Netherlands., Biemans VBC; UMC Utrecht, Utrecht, The Netherlands., Moes DJAR; Department of Clinical Pharmacy and Toxicology, Leiden University Medical Centre, Leiden, The Netherlands., Hoentjen F; Division of Gastroenterology, University of Alberta, Edmonton, Canada.; Department of Gastroenterology, Radboud University Medical Centre, Nijmegen, The Netherlands., Ter Heine R; Department of Pharmacy, Radboud Institute for Heulth Sciences, Radboud University Medical Center, Nijmegen, The Netherlands., Maljaars PWJ; Department of Gastroenterology and Hepatology, Leiden University Medical Centre, Albinusdreef 2, 2333 ZA, Leiden, The Netherlands., Theeuwen R; Department of Gastroenterology and Hepatology, Leiden University Medical Centre, Albinusdreef 2, 2333 ZA, Leiden, The Netherlands., Pierik M; MUMC+, Maastricht, the Netherlands., Duijvestein M; Department of Gastroenterology, Radboud University Medical Centre, Nijmegen, The Netherlands., van der Meulen-de Jong AE; Department of Gastroenterology and Hepatology, Leiden University Medical Centre, Albinusdreef 2, 2333 ZA, Leiden, The Netherlands. ae.meulen@lumc.nl.; Department of Gastroenterology and Hepatology, Amsterdam Gastroenterology Endocrinology Metabolism (AGEM) Research Institute, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands. ae.meulen@lumc.nl.
Jazyk: angličtina
Zdroj: Digestive diseases and sciences [Dig Dis Sci] 2023 Jun; Vol. 68 (6), pp. 2647-2657. Date of Electronic Publication: 2023 Mar 15.
DOI: 10.1007/s10620-023-07822-7
Abstrakt: 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.
(© 2023. The Author(s).)
Databáze: MEDLINE
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