ABSTRACT
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 µg/mL). Median wk6 ustekinumab level (n = 25) was 14.2 µg/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 µg/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 µg/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 µg/mL, P = 0.04. CONCLUSION: Wk6 ustekinumab levels are significantly associated with baseline Crohn's disease biomarkers and subsequent clinical and biochemical outcomes.
Subject(s)
Crohn Disease , Ustekinumab , C-Reactive Protein , Crohn Disease/chemically induced , Crohn Disease/diagnosis , Crohn Disease/drug therapy , Humans , Leukocyte L1 Antigen Complex , Remission Induction , Treatment Outcome , Ustekinumab/therapeutic useABSTRACT
Spread of the novel coronavirus SARS-CoV-2 has resulted in a global pandemic that is affecting the health and economy of all World Health Organization [WHO] regions. Clinical and translational research activities have been affected drastically by this global catastrophe. In this document we provide a suggested roadmap for resuming gastrointestinal translational research activities, emphasising physical distancing and use of personal protective equipment. We discuss modes of virus transmission in enclosed environments [including clinical workplaces and laboratories] and potential risks of exposure in the endoscopy environment for research staff. The proposed guidelines should be considered in conjunction with local institutional and government guidelines so that translational research can be resumed as safely as possible.