DOP103 Optimization of Ustekinumab Treatment Induction Using a Pharmacokinetic Model in Inflammatory Bowel Disease Patients

Abstract Background Therapeutic drug monitoring and pharmacokinetic modeling, implemented in the treatment of patients with inflammatory bowel disease (IBD), improve drug efficacy and reduce side effects. Recently, Ustekinumab (UST) levels associated with therapeutic targets have been established, principally during induction, highlighting the need for appropriate optimization of this phase to improve response to UST treatment. Objectives To evaluate the effectiveness of proactive dose optimization of UST using pharmacokinetic modeling during induction (target concentration at week 8) in the treatment of IBD with UST. Methods A prospective comparative study was conducted on IBD patients initiating UST treatment, divided into two groups: standard induction protocol (initial intravenous UST dose adjusted to weight) or optimized induction protocol (following the initial weight-adjusted intravenous UST dose, UST levels were measured at 4 weeks and, using a pharmacokinetic model—including weight, height, and serum albumin levels—induction dosing was adjusted). UST plasma concentration was measured by FIA at 4 weeks in the optimized group and at 8 weeks from treatment initiation in all patients. Data on IBD and the clinical status of patients at UST treatment initiation were reviewed. Results A total of 88 patients were included: 72 in the standard protocol group (male 52.8%; Crohn's disease 59.2%; prior biologic use 95.8%; fecal calprotectin >150 g/kg 61.5%) and 16 in the optimized group (male 56.3%; Crohn's disease 68.8%; prior biologic use 93.88%; fecal calprotectin >150 g/kg 68.8%), with no significant differences in baseline characteristics between groups. The mean UST concentration at the end of induction (8 weeks) was significantly higher in patients with optimization via pharmacokinetic model compared to the standard protocol (15.4 [10.4-20.3] µg/ml vs 9.2 [7.7-10.7] µg/ml; p>0.0018) (Fig. A). In the optimized group, 6 patients (37.5%) received additional intravenous UST doses (3 patients received 1 dose and 3 patients received 2 doses before week 8). The percentage of patients achieving a UST concentration ≥ 6.6 µg/ml (linked to biochemical remission at weeks 12 and 24) and ≥ 9 µg/ml (associated with treatment durability ≥ 12 months) was significantly higher in the optimized group compared to those on the standard protocol (Figs. B and C). Conclusion Optimized UST treatment, through proactive dose adjustment based on pharmacokinetic modeling, achieves a target UST concentration during induction that should ensure treatment efficacy.