Impact of Precision-Guided Dosing on Clinical Decision-Making and Health Care Utilization in Inflammatory Bowel Disease: A Retrospective Pretest/Posttest Real-World Study

Abstract

Background: Precision-guided dosing (PGD) is a personalized tool that optimizes clinical decision-making in the treatment of inflammatory bowel disease (IBD) with infliximab (IFX) and its biosimilars. PGD employs nonlinear mixed-effect models using patient-specific pharmacokinetic parameters to predict infliximab trough concentrations without the need to wait until the actual trough measurement. This approach calculates patient-specific clearance (CL) and provides tailored IFX dosing and administration intervals aimed at achieving target trough levels. Implementing PGD can enhance treatment outcomes in IBD patients and may potentially reduce healthcare expenditures.

Methods: We conducted a multicenter, retrospective study as a follow up to our previous clinical experience program (CEP). We aimed to evaluate the impact of PGD on clinical decision-making, patient outcomes, healthcare utilization, and expenditures. Treatment decisions included: IFX dose intensification, reduction, discontinuation, or continuation. Disease activity and healthcare resource utilization and costs in the 12 months pre- and post-test were compared. Disease activity was measured using the physician global assessment (PGA) as follows: remission (0), mild (1), moderate (2), and severe (3). Costs were calculated based on modeling pre-established literature data.

Results: Analysis of data from 82 patients across 7 states and Puerto Rico showed that PGD-driven therapeutic decision making led to IFX treatment intensification (27%) or discontinuation (7%) in patients with low forecasted trough IFX concentrations, high clearance, and presence of antidrug antibody. Conversely, IFX dosage was reduced (18%) or unchanged (48%) for patients with high IFX concentrations and low clearance. There was a significant association between forecasted trough IFX levels and treatment modifications (P < .001). High clearance (> 0.294 L/day) was significantly associated with therapy intensification (OR 6.22, 95% CI: 2.19-19.8; P < .001). Following PGD, disease activity improved significantly (observed mean difference in physician global assessment: 0.378, P = 0.008) and healthcare resource utilization decreased. Across the entire patient population, hospitalizations decreased from 30 events pretest to 5 events posttest (P < .001), leading to overall cost saving.

Conclusions: HCPs used the PGD test to guide treatment decisions. PGD-driven optimization of IFX therapy led to improved patient outcomes, lower healthcare utilization, and cost savings.

Keywords: dose optimization; healthcare costs; novel laboratory developed test; pharmacokinetics; precision medicine; precision-guided dosing; therapeutic drug monitoring.

Graphical Abstract

Figure 1.

Disease activity before (pre) and ~12 months after (post) PGD test.

Figure 2.

Percentage of patients with low forecasted trough IFX concentration < 5 µg/mL, accelerated clearance > 0.294 L/day, and detectable levels of anti-drug antibodies (> 3.1 U/mL) in the 4 patient groups (Reduction, Continuation, Intensification, and Discontinuation). The numbers above the bars represent percentages, while the number inside the bars indicate the number of patients in each group presenting with forecasted trough IFX concentration < 5 µg/mL, clearance > 0.294 L/day, and detectable levels of anti-drug antibodies (ATI > 3.1 U/mL)