P555 Ustekinumab tissue and serum levels in patients with Crohn’s disease are closely correlated though not consistently associated with objective response after induction.
Proietti, E.(1,2);Bayoumy, A.(1);Pauwels, R.(1);van der Woude, J.(1);Doukas, M.(3);Oudijk, L.(3);Peppelenbosch, M.(1);Grohmann, U.(2);Crombag, R.(4);de Vries, A.(1);Fuhler, G.(1);
(1)Erasmus Medical Center, Department of Gastroenterology and Hepatology, Rotterdam, The Netherlands;(2)University of Perugia, Department of Medicine and Surgery, Perugia, Italy;(3)Erasmus Medical Center, Department of Pathology, Rotterdam, The Netherlands;(4)Erasmus Medical Center, Department of Hospital Pharmacy, Rotterdam, The Netherlands;
Background
Ustekinumab (UST), which targets p40 of IL23/IL12, is an effective treatment for Crohn’s disease (CD). Therapeutic drug monitoring (TDM) may optimize UST posology. The aim of this study was to investigate UST and IL23 serum and tissue concentrations in relation to mucosal inflammation and treatment response.
Methods
A prospective cohort study was performed in adult CD patients who initiated UST at Erasmus MC, the Netherlands, between December 2016 and November 2018. Endoscopies were performed at baseline and week 16. UST and IL23 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 GHAS score ≤4.
Results
All 56 included patients were previously treated with anti-TNFα-inhibitors prior to UST. Upon treatment with UST, 17 (30%) showed clinical response, 16/53 (30%) biochemical response, and 20/56 (36%) endoscopic response. UST, but not IL23, concentration in biopsies was correlated to levels in corresponding sera (p < 0.0001). No correlation was found between UST serum and tissue levels with clinical or endoscopic response, or histological remission. However, patients achieving biochemical response showed significantly higher UST serum levels as compared to those without biochemical response (3.12 µg/ml vs 1.41 µg/ml, p = 0.01). Furthermore, tissue IL23/UST ratio correlated with histologic mucosal inflammation (p = 0.01).
Conclusion
This is the first study to demonstrate a correlation between serum and tissue UST levels. We showed that the tissue IL23/UST ratio correlated with mucosal inflammation. UST tissue concentrations did not correlate with treatment response, while UST serum concentrations were associated with biochemical response at week 16. The role of UST levels for TDM in IBD warrants further research.