PRECISION-GUIDED DOSING OF INFLIXIMAB IN IBD: INSIGHTS FROM THE BAYESIAN ESTIMATE SUSTAINING TROUGH (BEST) STUDY

Abstract BACKGROUND Sustaining therapeutic exposure aligned with disease control is essential for the long-term success of infliximab (IFX) in inflammatory bowel disease (IBD). The Bayesian Estimate Sustaining Trough (BEST) study evaluated the clinical utility of a precision-guided dosing (PGD) tool and pharmacokinetic (PK) metrics, specifically IFX concentration and clearance (CL), to inform individualized dosing strategies. METHODS Patients with IBD receiving maintenance IFX therapy were prospectively enrolled from November 2023 to January 2025 across three North American centers, representing two academic medical centers and one community-based gastroenterology practice. The PGD tool (PredictrPK IFX Maintenance test) measured current IFX and anti-drug antibody levels, estimated trough concentrations, calculated IFX CL (L/day), and proposed dosing regimens to achieve target exposure. Serum samples were processed by an accredited clinical pharmacokinetics laboratory (Prometheus Laboratories, San Diego, CA). Outcomes included changes in IFX dosing and PRO2-based clinical remission, assessed at each treatment cycle. Statistical analyses included Kruskal-Wallis, Fisher test, and logistic regression. RESULTS Ninety-seven patients were enrolled (Table 1), with 296 specimens analyzed (93% proactively). Most patients were in clinical remission (82%), with 90% of cycles showing trough IFX concentrations ≥10 μg/mL and a low incidence of immunization (3%). Following PGD reporting, IFX therapy was reduced (17 cycles, 82% in remission), continued (238 cycles, 84% in remission), intensified (37 cycles, 70% in remission), or discontinued (4 cycles, 25% in remission). Dose intensification was associated with significantly lower concentrations, while dose continuation and reduction correlated with lower CL (Table 2). Clinical remission was associated with lower CL (median 0.244 L/day [IQR: 0.180-0.308 L/day] vs. 0.279 [IQR: 0.231-0.327 L/day], p = 0.005), with no significant difference in trough concentrations. Patients with CL < 0.248 L/day were 2.7 times more likely to be in remission (95% CI: 1.4–5.2, p < 0.01), with a similar trend for those with concentrations >20 μg/mL (OR = 2.1, p = 0.08). CONCLUSION PGD demonstrated clinical utility in informing individualized IFX therapy for IBD, with dosing decisions aligned to pharmacokinetic profiles and clinical outcomes. CL was a strong predictor of clinical remission, reinforcing its role as a key parameter in therapeutic monitoring. PGD guided adjustments, whether intensification, continuation, or reduction, were associated with distinct PK patterns and remission rates, supporting its value in treatment optimization. Importantly, elevated CL identified a subgroup of patients with adequate drug exposure but suboptimal disease control, likely reflecting persistent inflammatory burden.