Abstract
Background
Despite the therapeutic efficacy of Ustekinumab (UST) in Crohn's disease (CD), loss
of response (LOR) is observed over time. This study aims to evaluate the impact of
the UST pharmacokinetics (PK) at induction on clinical and endoscopic outcomes, as
well as to find predictive markers of UST response.
Methods
This retrospective study included 80 CD patients. Pharmacokinetics data (trough levels
(TLs)) combined with clinical and biological parameters were fed into tailored logistic
regression and tree-based ensemble techniques to predict clinical and endoscopic outcomes
at one year of follow-up.
Results
TLs at week 16 were significantly lower among patients with moderate to severe endoscopic
activity during the follow-up (p = 0.04). The best model to predict endoscopic outcome was obtained at week 16 by
Random Forest with an area under the receiver operating characteristic curve of 0.92 ± 0.08,
sensitivity 91% and specificity 75%, with key inputs such as lymphocyte and monocyte
counts at week 8, and UST TLs and CRP at week 16.
Conclusions
This real-world study confirms the relationship between early UST TLs and both clinical
and endoscopic outcomes. Models were developed for the task of predicting clinical
and endoscopic remission in CD patients treated with UST, highlighting the clinical
relevance of UST TLs at week 16.
Keywords
Abbreviations:
ATU (Antibodies to ustekinumab), CD (Crohn’s disease), CRP (C-reactive protein), IMM (Immunosuppressor), LOR (Loss of response), PK (Pharmacokinetics), RCT (Randomized control trial), ROC (Receiver operating characteristic curve), UST (Ustekinumab), TDM (Therapeutic drug monitoring), TL (Trough level)To read this article in full you will need to make a payment
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Article info
Publication history
Published online: August 14, 2022
Accepted:
July 19,
2022
Received:
April 19,
2022
Identification
Copyright
© 2022 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.
