P810 Association between Ustekinumab Trough Levels, Serum IL-22 and Oncostatin M Levels with Clinical and Biochemical Outcomes in Patients With Crohn’s Disease

Abstract Background Ustekinumab is an effective treatment for patients with Crohn’s disease (CD). Strategies to monitor response to therapy may improve clinical control of the disease and reduce economical costs. Therefore, we aimed to evaluate if trough levels (TL) of ustekinumab, serum IL22 and oncostatin M levels could be considered early markers of non-response assessing their correlation with clinical and biochemical outcomes in CD. Methods We consecutively recruited patients with CD treated with ustekinumab from October 2018 to September 2020. Clinical and biochemical data were collected at baseline, at weeks 12 and 24. TL were dosed at week 12 and week 24, IL22 levels and oncostatin M serum levels were dosed at baseline and at week 12. A primary analysis determined if TL, IL22 levels and Oncostatin M serum levels were associated with clinical response (reduction in Harvey Bradshaw Index score of at least 3 points), clinical remission (Harvey Bradshaw Index score <5) and biochemical remission (negative C-reactive protein (CRP) or fecal calprotectin levels (FC) <250 μg/g). A Shapiro-Wilk test was conducted to test for normality for all variables and a Mann Whitney test was used to evaluate correlation of TL, IL22 and Oncostatin M serum levels with HBI index variation and biochemical remission. Results Among 84 patients enrolled, 10 were excluded because they were lost to follow up or had incomplete data. At week 24, 59.4% of patients had a clinical response and 47.9% were in clinical remission. TL dosed at week 12 significantly correlated with clinical response at week 12 (p=0.047) and at week 24 (p=0.019) and with clinical remission at week 12 (p=0.02) and at week 24 (p=0.02). TL at week 12 also correlated with biochemical remission both at week 12 (CRP and FC normalization, p<0.001 and p=0.04, respectively) and at week 24 (CRP and FC normalization, both p=0.01). At week 24, patients with positive FC had higher median trough concentrations of ustekinumab than those with negative FC (p=0.01). Oncostatin M levels at baseline significantly correlated with FC levels at week 12 (p<0.001) and at week 24 (p=0.04), but did not correlate with clinical remission. IL22 levels at baseline were lower in patients in clinical and biochemical remission at week 24, although these trends did not reach statistical significance (p=0.43 and p=0.86). Conclusion Ustekinumab was an effective therapy in patients with CD. TL at week 12 were predictive of both clinical and biochemical remission at week 12 and 24. Oncostatin M levels at baseline significantly correlated with FC levels at week 12 and 24.