Ustekinumab Tissue and Serum Levels in Patients with Crohn's Disease Are Closely Correlated though Not Consistently Associated with Objective Response after Induction

Abstract

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