Journal
INFLAMMATORY BOWEL DISEASES
Volume 29, Issue 7, Pages 1038-1046Publisher
OXFORD UNIV PRESS INC
DOI: 10.1093/ibd/izac169
Keywords
therapeutic drug monitoring; Crohn's disease; ustekinumab; trough concentrations; IL-23
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This study is the first to demonstrate a correlation between serum and tissue UST levels. The tissue IL-23-to-UST ratio correlated with mucosal inflammation, and UST serum levels were more indicative of biochemical response.
Background Ustekinumab (UST), which targets p40/interleukin (IL)-23 and IL-12, is an effective treatment for Crohn's disease (CD). Therapeutic drug monitoring may optimize UST posology. The aim of this study was to investigate UST and IL-23 serum and tissue concentrations in relation to mucosal inflammation and treatment response at an early time point. Methods CD patients starting UST between December 2016 and November 2018 were prospectively enrolled. Endoscopies were performed at baseline and week 16. UST and IL-23 serum and tissue concentrations were measured at week 16. Clinical and biochemical response were defined as decline of >= 3 points in Harvey-Bradshaw Index and reduction of >= 50% in fecal calprotectin levels. Endoscopic response was defined as a >= 50% decline in Simple Endoscopic Score or a decline of >= 1 points in Rutgeerts score. Histological remission was defined as Global Histologic Disease Activity Score <= 4. Results Of 56 included patients, 17 (30%) of 56 showed clinical response, 16 (30%) of 53 showed biochemical response, and 20 (36%) of 56 showed endoscopic response. UST, but not IL-23, concentration in biopsies was correlated to levels in corresponding sera (P < .0001). No correlation was found between UST tissue levels and treatment response. Patients achieving biochemical response showed significantly higher UST serum levels (3.12 mu g/mL vs 1.41 mu g/mL; P = .01). Tissue IL-23-to-UST ratio correlated with mucosal inflammation (P = .01). Conclusions This is the first study to demonstrate a correlation between serum and tissue UST levels. While tissue IL-23-to-UST ratio correlated with mucosal inflammation, UST serum levels were more indicative for biochemical response. The role of UST levels for therapeutic drug monitoring in inflammatory bowel disease needs further research. Lay Summary Ustekinumab (UST) serum levels correlate with UST tissue levels in patients with Crohn's disease. Tissue interleukin-23-to-UST ratio correlates with histological inflammation (Global Histologic Disease Activity Score). Serum UST levels correlate with biochemical response (reduction of >= 50% in fecal calprotectin levels).
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