S824 Cost-Effectiveness of Precision-Guided Dosing in Adult Crohn’s Disease Patients Initiating Infliximab Maintenance Therapy

Abstract

Introduction: Crohn’s disease (CD) patients that lose response to biologics experience reduced quality of life (QoL) and costly hospitalizations. Precision-guided dosing provides clinicians with a comprehensive pharmacokinetic (PK) profile that allows for the next biologic dose to be personalized. We analyzed the cost-effectiveness of infliximab (IFX) Precision-guided dosing relative to two IFX dose intensification strategies (DIS). Methods: We developed a hybrid (Markov and decision tree) model of CD patients who had a clinical response to IFX induction and entered IFX maintenance in “remission” or “mild symptoms” health states. The analysis took a US payer perspective, a time horizon of 2 years in the base case, and a cycle length of 4 weeks. There were 3 comparators for IFX dosing: Precision-guided dosing, dose intensification based on symptoms, inflammatory markers, and trough IFX concentration (DIS1), and IFX dose intensification based on symptoms alone (DIS2). Patients that failed IFX initiated ustekinumab (UST), followed by vedolizumab, and conventional therapy. Transition probabilities for IFX were estimated from real-world clinical PK data and interventional clinical trial (PMID: 34978325; 29317275) patient-level data. All other transition probabilities were derived from published randomized clinical trials and cost-effectiveness analyses. Utility values were sourced from previous health technology assessments. Direct costs included biologic acquisition and infusion, surgeries and procedures, conventional therapy, and lab testing. The primary outcomes were total discounted costs, total quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs). The robustness of results was assessed via one-way sensitivity and scenario analyses. Results: Total costs and QALYs at 2 years are presented in Table. The ICERs of Precision-guided dosing relative to DIS1 and DIS2 were 171,810 and 127,990, respectively. One-way sensitivity analyses (Figure) demonstrated that the cost-effectiveness of Precision-guided dosing was most sensitive to the time between IFX doses. Precision-guided dosing had the lowest proportion of patients requiring a new biologic through 2 years (0.5% vs 2.4% and 27.7% for DIS1 and DIS2, respectively). Conclusion: Precision-guided dosing provides substantial clinical and QoL benefits for adult CD patients by maintaining clinical remission and avoiding IFX failure; it is cost-effective relative to other DISs at a WTP of $175,000/QALY.Figure 1.: Precision-guided Dosing ICER Relative to DIS2 † Varied by ±10% * Varied by ±5% CD: Crohn's disease, DIS: dose intensification strategy, ICER: incremental cost-effectiveness ratio, IFX: infliximab, M-S: moderate-severe, PMPM: per member per month, Rem: remission Table 1. - Base Case Results (2-year Horizon Discounted) DIS Total QALYs Total Costs ICER Relative to Precision-guided Dosing ICER Relative to DIS1 ICER Relative to DIS2 Incremental NMB vs DIS1 (WTP $150,000/QALY) Incremental NMB vs DIS1 (WTP $50,000/QALY) Incremental NMB vs DIS2 (WTP $150,000/QALY) Incremental NMB vs DIS2 (WTP $50,000/QALY) Precision-guided Dosing* 1.572 $50,753 - 171,810 127,990 -$765 -$4,274 $1,816 -$6,436 DIS1† 1.537 $44,725 171,810 - 95,581 - - $2,581 -$2,162 DIS2 ‡ 1.489 $40,191 127,990 95,581 - -$2,581 $2,162 - - DIS: dose intensification strategy, ICER: incremental cost-effectiveness ratio, NMB: net monetary benefit, QALY: quality-adjusted life year, WTP: willingness to pay.*Model informed precision dosing with homogenous mobility shift assay (Prometheus Laboratories).†Dose intensification based on a combination of symptoms, inflammatory markers and proactive therapeutic drug monitoring. Corresponds to cohorts 1 and 2 of the TAILORIX clinical trial.‡Dose intensification reactive on symptoms only. Corresponds to cohort 3 of the TAILORIX clinical trial.