TY - JOUR
T1 - Ustekinumab Trough Concentrations Are Associated with Biochemical Outcomes in Patients with Crohn's Disease
AU - Straatmijer, T.
AU - Biemans, V.B.C.
AU - Moes, D.J.A.R.
AU - Hoentjen, F.
AU - ter Heine, R.
AU - Maljaars, P.W.J.
AU - Theeuwen, R.
AU - Pierik, M.
AU - Duijvestein, M.
AU - van der Meulen-de Jong, A.E.E.
AU - Dutch Initiative on Crohn's and Colitis (ICC)
N1 - Funding Information:
Nothing to declare.
Publisher Copyright:
© 2023, The Author(s).
PY - 2023/6
Y1 - 2023/6
N2 - ObjectiveIt 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.MethodsWe 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).ResultsIn 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 mu g/mL versus 3.9 mu g/mL, P < 0.01 and 6.3 mu g/mL versus 3.9 mu g/mL, P < 0.01, respectively). In quartile analysis, patients with UST levels in the highest quartile (>= 6.3 mu g/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.ConclusionIn this real-world cohort of patients with CD, UST levels in the highest quartile (>= 6.3 mu g/mL) at week 8 were associated with higher biochemical remission rates at week 24.
AB - ObjectiveIt 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.MethodsWe 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).ResultsIn 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 mu g/mL versus 3.9 mu g/mL, P < 0.01 and 6.3 mu g/mL versus 3.9 mu g/mL, P < 0.01, respectively). In quartile analysis, patients with UST levels in the highest quartile (>= 6.3 mu g/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.ConclusionIn this real-world cohort of patients with CD, UST levels in the highest quartile (>= 6.3 mu g/mL) at week 8 were associated with higher biochemical remission rates at week 24.
KW - Ustekinumab
KW - Pharmacokinetics
KW - Crohn's disease
KW - Inflammatory bowel disease
KW - SUBCUTANEOUS USTEKINUMAB
KW - THERAPY
KW - SERUM
U2 - 10.1007/s10620-023-07822-7
DO - 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 -