Ustekinumab induction concentrations are associated with clinical and biochemical outcomes at week 12 of treatment in Crohn's disease

Background We investigated relationships between induction ustekinumab levels and clinical and biochemical outcomes in Crohn's disease. Methods Following standard IV induction, ustekinumab levels were measured at week 2 (wk2) and week 6 (wk6). Ustekinumab levels were compared in patients receiving 260, 390 and 520 mg at induction. Crohn's disease activity index (CDAI), serum albumin, C-reactive protein (CRP) and fecal calprotectin (FCP) were measured at baseline and week 12 (wk12). Associations between ustekinumab levels and these parameters were assessed. Ustekinumab levels were compared between patients requiring dose intensification within one year of induction and those remaining on standard dosing. Results Of 23 wk2 ustekinumab levels, 22(95.7%) were above the upper limit of quantification of the assay (25 mu g/mL). Median wk6 ustekinumab level (n = 25) was 14.2 mu g/mL [interquartile range (IQR), 9.6-20.1]. Median wk6 ustekinumab levels in patients receiving 260, 390 and 520 mg were 8.6, 16.3 and 25.0 mu g/mL, respectively, P = 0.01. There were significant correlations between baseline albumin and wk6 ustekinumab levels; r = 0.644 [95% confidence interval (CI), 0.304-0.839], P < 0.001, and between baseline FCP and wk6 ustekinumab levels; r = -0.678 (95% CI, -0.873 to -0.296), P < 00.01. Median wk12 CDAI (n = 18), CRP (n = 22) and FCP (n = 13) were 78 (IQR, 52.5-152), 1.75 mg/L (IQR, 0.93-7.03) and 746 mu g/g (IQR, 259-2100), respectively. There were significant correlations between wk6 ustekinumab levels and wk12 CDAI; r = -0.513 (95% CI, -0.796 to -0.046), P = 0.03; and between wk6 ustekinumab levels and wk12 CRP; r = -0.578 (95% CI, -0.808 to -0.194), P < 0.01. Wk6 ustekinumab levels were lower in patients undergoing subsequent dose intensification; 12.5 vs. 19.6 mu g/mL, P = 0.04. Conclusion Wk6 ustekinumab levels are significantly associated with baseline Crohn's disease biomarkers and subsequent clinical and biochemical outcomes. Copyright (C) 2021 Wolters Kluwer Health, Inc. All rights reserved.