TY - JOUR
T1 - Ustekinumab Trough Concentrations Are Associated with Biochemical Outcomes in Patients with Crohn’s Disease
AU - Straatmijer, Tessa
AU - Biemans, Vince B. C.
AU - Moes, Dirk Jan A. R.
AU - Hoentjen, Frank
AU - ter Heine, Rob
AU - Maljaars, P. W. Jeroen
AU - Theeuwen, Rosaline
AU - Pierik, Marieke
AU - Duijvestein, Marjolijn
AU - the Dutch Initiative on Crohn’s and Colitis (ICC)
AU - van der Meulen-de Jong, Andrea E.
N1 - Funding Information: Nothing to declare. Publisher Copyright: © 2023, The Author(s).
PY - 2023/6
Y1 - 2023/6
N2 - 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.
AB - 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.
KW - Crohn’s disease
KW - Inflammatory bowel disease
KW - Pharmacokinetics
KW - Ustekinumab
UR - http://www.scopus.com/inward/record.url?scp=85150179170&partnerID=8YFLogxK
U2 - https://doi.org/10.1007/s10620-023-07822-7
DO - https://doi.org/10.1007/s10620-023-07822-7
M3 - Article
C2 - 36920666
SN - 0163-2116
VL - 68
SP - 2647
EP - 2657
JO - Digestive Diseases and Sciences
JF - Digestive Diseases and Sciences
IS - 6
ER -