P0801Optimising ustekinumab therapy in Inflammatory Bowel Disease: benefits of early pharmacokinetic model-guided reinduction.

Abstract Background Therapeutic drug monitoring of ustekinumab has gained relevance in the management of inflammatory bowel disease (IBD), particularly in patients with suboptimal or secondary loss of response. Intravenous reinduction is used to restore therapeutic efficacy, although evidence supporting pharmacokinetic (PK) model–guided optimisation remains limited. Comparing PK-guided reinduction with empiric reinduction may provide valuable insights to optimise treatment and advance therapeutic individualisation. Methods A retrospective, observational, single-centre study including patients with IBD treated with ustekinumab who required intravenous reinduction was conducted. Two cohorts were compared: one managed using a PK model (n = 12), in which drug levels were monitored closely from the start to guide maintenance dosing, and another undergoing standard reinduction without PK guidance (n = 30), in which no drug levels were measured. Follow-up lasted 12 months. The primary objective was to assess whether PK model–guided reinduction was associated with improved clinical and biochemical outcomes. Secondary objectives included evaluating loss of response, need for additional interventions (corticosteroids or surgery), treatment switching, and the accuracy of the model in estimating serum ustekinumab concentrations. Results Forty-two patients were included (50% female): 32 with Crohn’s disease and 9 with ulcerative colitis. Perianal involvement was less frequent in the PK-guided cohort (8% vs 27%). After 12 months, secondary loss of response leading to biologic switch occurred in 25% of PK-guided patients and 43% of the standard group; two patients in the latter required subsequent PK-guided reinduction. Additional interventions were uncommon (one hospitalisation and corticosteroid course per cohort; no surgeries). In the PK-guided group, a more pronounced and sustained reduction in faecal calprotectin and C-reactive protein was observed, accompanied by progressive increases in albumin and haemoglobin, indicating more stable inflammatory and nutritional control. Concordance between PK model–predicted and measured serum ustekinumab levels, assessed using Bland–Altman analysis, demonstrated satisfactory agreement, supporting the reliability and potential clinical utility of the pharmacokinetic approach. Conclusion Pharmacokinetic model–guided ustekinumab reinduction is associated with more sustained biochemical improvement and a lower trend towards loss of response compared with standard reinduction. These findings highlight the potential of PK-guided strategies to optimise treatment in IBD and provide real-world evidence supporting their clinical relevance, while acknowledging that confirmatory prospective studies are warranted. References: 1. Iniesta-Navalón C, Ríos-Saorín M, Rentero-Redondo L, Nicolás-de Prado I, Gómez-Espín R, Urbieta-Sanz E. Impact of ustekinumab exposure on clinical outcomes during induction in inflammatory bowel disease. Rev Esp Enferm Dig. 2024. 2. Saleh A, Stading R, Miroballi N, Glassner K, Abraham BP. Therapeutic drug monitoring in patients with inflammatory bowel disease on ustekinumab. Hematology. 2024;29(2):13264. 3. Petrov J, Fine S, Alzahrani R, Mohamed G, Al-Bawardy B. Ustekinumab drug levels and outcomes in inflammatory bowel disease. J Clin Med. 2025;14(2):529. 4. Battat R, Kopylov U, Bessissow T, et al. Ustekinumab trough concentrations are associated with biochemical outcomes in patients with Crohn’s disease. Clin Gastroenterol Hepatol. 2017;15(9):1427-1434. Conflict of interest: Ms. Molinillo Marín, Angélica: No conflict of interest Barroso Castro, Jaime: No conflict of interest Arosa Perez, Miriam: No conflict of interest San Felix Carrasco, Mirari: No conflict of interest Arias Fernández, Laura: No conflict of interest Casas Arrate, Javier: No conflict of interest Baza Martinez, Beatriz: No conflict of interest Perez Fernandez, Silvia: No conflict of interest Casado Morentin, Ignacio: No conflict of interest Gomez Irwin, Laura: No conflict of interest