P542 Clinical decision support tool guided selective intensive induction strategy of ustekinumab in patients with Crohn’s disease: real-world evidence

Abstract

Abstract Background Clinical decision support tool (CDST) of ustekinumab (UST) can predict the possibility of drug response1. However, the potential benefits of initial intensification induction therapy (IIT) to improve clinical outcomes for different responders has not been explored2. We aimed to evaluate the effectiveness and safety of the strategy of initial IIT for Crohn’s disease patients who exhibit varying responses based on UST-CDST. Methods This is a multicenter retrospective study included active Crohn’s disease patients who were low, intermediate and high probability responders according to UST-CDST (Figure 1). IIT was defined as intensive induction by 2 or 3 initial doses of a weight-based intravenous UST. The patients treated with standard therapy (ST) were identified as controls. The primary endpoint was corticosteroid-free clinical remission (CFCR) at week 24. The secondary endpoint was clinical remission, clinical response, endoscopic remission, endoscopic response, and CRP normalization at week 24. Propensity-matched analyses were applied to ensure comparability. Results A total of 296 patients were included, with 69 patients receiving IIT and 227 patients receiving ST. At week 24, in low-intermediate probability responders, IIT group was associated with higher rates of CFCR (72.3% vs 43.0%, OR 3.47 [95%CI 2.15-5.68], clinical remission (77.3% vs 47.1%, OR 3.82 [95%CI 2.33-6.37]), clinical response (78.1% vs 60.1%, OR 2.37 [95%CI 1.43-3.97]), endoscopic remission (50.6% vs 22.4%, OR 3.55 [95%CI 1.65-7.92]) and endoscopic response (83.1% vs 44.1%, OR 6.23 [95%CI 2.75-15.26]). CRP normalization were comparable. In high probability responders, all end points did not demonstrate statistically significant differences (Table 1). The cut-off UST trough concentration for predicting corticosteroid-free clinical remission was determined to be 1.43µg/mL, with an area under the curve (AUC) of 0.612, a sensitivity of 55.0%, and a specificity of 70.0%. No serious adverse events occurred. Conclusion Initial dose intensification induction in low-intermediate responders based on UST-CDST was superior to the ST in both clinical and endoscopic remission at week 24, which provide a novel strategy for stratifying patients at baseline. 1. Park J, Chun J, Yoon H, Cheon JH. Feasibility of a Clinical Decision Support Tool for Ustekinumab to Predict Clinical Remission and Relapse in Patients With Crohn's Disease: A Multicenter Observational Study. Inflamm Bowel Dis. 2023;29(4):548-554. 2. Ren H, Kang J, Wang J, et al. Efficacy of Ustekinumab Optimization by 2 Initial Intravenous Doses in Adult Patients With Severe Crohn's Disease [published online ahead of print, 2023 Aug 24]. Inflamm Bowel Dis. 2023; izad184.