Impact of ustekinumab exposure on clinical outcomes during induction in inflammatory bowel disease

Abstract

BACKGROUND: understanding the relationship between ustekinumab (UST) exposure and clinical outcomes in inflammatory bowel disease (IBD) induction is crucial. However, evidence remains limited, highlighting the need to comprehend UST's pharmacokinetic variability for tailored treatments. AIMS: this study aimed to investigate the association between UST exposure during the induction phase and clinical outcomes and identifying factors associated with UST exposure during this period. METHODS: a retrospective observational study was conducted on a cohort of consecutive IBD patients. The primary endpoint was to assess the association between UST exposure at week 8 and both clinical and biochemical remission at week 26, as well as the absence of disease flare-ups during the initial six months of treatment. The secondary endpoint was to investigate the relationship between baseline characteristics and UST exposure at week 8. RESULTS: a total of 56 IBD patients were included. Variables associated with adequate UST exposure included baseline fecal calprotectin < 500 µg/g (OR: 7.72 [95 % CI: 1.75-34.03]) and female sex (OR: 4.56 [95 % CI: 1.12-18.60]). A cut-off UST trough levels of 8.3 ?g/ml yielded an area under the curve (AUC) of 0.74 (95 % CI: 0.58-0.90, p = 0.021) to predict normal fecal calprotectin levels, and 8.6 µg/ml resulted in an AUC of 0.724 (95 % CI: 0.558-0.863) to predict clinical remission. CONCLUSIONS: this study demonstrates a significant association between UST concentrations and clinical and biochemical remission in IBD patients. Results suggest that standard induction doses may not be sufficient for all patients, highlighting the importance of treatment individualization to optimize outcomes.