P0975 Cost-effectiveness analysis of anti-TNF treatment from diagnosis for patients with moderate and severe Crohn’s disease: an analysis using data from the PROFILE trial
Authors: Noor N , Davies N , Tahir W , Bond S , Dowling F , Brezina B , Patel K , Lee J , Lyons P , McKinney E , Smith K , Buchanan V , Parkes M ,   PROFILE Study Group
Published: January 2025

Abstract

Background
The PROFILE trial in patients with newly-diagnosed Crohn’s disease demonstrated that “top-down” therapy, with combination infliximab and immunomodulator from diagnosis, provided superior efficacy and a better safety profile over a one-year follow-up period compared to an “accelerated step-up” approach. The current study aims to evaluate cost-effectiveness by assessing the healthcare cost and health outcomes associated with starting anti-TNF medication as soon as possible after diagnosis.

Methods
A de novo Markov model was developed to model the cost-effectiveness of using a “top-down” compared to “accelerated step-up” strategy in adults newly-diagnosed with moderate and severe Crohn’s disease. The model structure included three possible mutually exclusive health states (active disease, inactive disease and death). Use of infliximab and adalimumab from diagnosis was modelled with biosimilar costs based on average real-world UK contract drug costs ascertained from 20 PROFILE trial sites in 2024. Parameters were informed by individual patient data from PROFILE and data from the published literature. Key model outcomes included healthcare costs (drug acquisition, drug administration, surgery, hospitalisation, disease management) and health outcomes (quality-adjusted life years gained [QALYs]) measured over a 5-year time horizon.

Results
The base case cost-effectiveness analysis indicates that a “top-down” strategy dominates over an “accelerated step-up” approach. Initiating infliximab from the point of diagnosis yields greater clinical benefits, with an incremental gain of 0.17 QALYs per patient over a 5-year period, and is less costly, saving £1034 per patient over the same time frame. Similar clinical benefits were obtained when modelling use of adalimumab treatment from diagnosis, with even greater cost savings, totalling £9412 per patient over 5 years. Sensitivity analysis further supports robustness of the “top-down” approach, showing it to be the most cost-effective option in 97.6% of model simulations, based on a commonly applied UK decision-maker willingness-to-pay threshold of £30000 per QALY.

Conclusion
This health economic analysis demonstrates that “top-down” treatment with anti-TNF therapy from diagnosis results in lower healthcare resource use compared to an “accelerated step-up” strategy. The economic benefits align with improved clinical outcomes, as early, effective treatment better controls inflammation. Patients experience longer periods in remission, fewer disease-related flares, and enhanced quality of life. In newly-diagnosed patients with moderate and severe Crohn’s disease, “top-down” treatment with anti-TNF therapy is more efficacious, safer and cost-efficient than an “accelerated step-up” treatment strategy.

References
Noor NM et al. A biomarker-stratified comparison of top-down versus accelerated step-up treatment strategies for patients with newly diagnosed Crohn’s disease (PROFILE): a multicentre, open-label randomised controlled trial. Lancet Gastroenterol Hepatol. 2024 May;9(5):415-427.