Introduction

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 a conventional “accelerated step-up” management approach.

Aims & Methods

The current study aimed to evaluate cost-effectiveness by assessing the healthcare cost and health outcomes associated with starting anti-TNF medication (intravenous infliximab, subcutaneous infliximab, subcutaneous adalimumab) as soon as possible after diagnosis. 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 active Crohn’s disease (HBI score >7, elevated CRP and/or faecal calprotectin >200ug/g and endoscopic evidence of disease activity with simple endoscopic score of Crohn’s disease activity of >6 [>4 if ileal-only disease]). Parameters were informed by individual patient data from PROFILE and data from the published literature. Use of intravenous infliximab, or subcutaneous infliximab, or subcutaneous adalimumab from diagnosis were modelled with biosimilar costs based on average real-world UK contract drug costs ascertained from 18 PROFILE trial sites in 2024. Key model outcomes included healthcare costs (drug acquisition, drug administration, disease management, hospitalisation, surgery) and health outcomes (quality-adjusted life years gained [QALYs]) measured over a 5-year time horizon.

Results

The base case cost-effectiveness analysis indicated that a “top-down” strategy dominated over an “accelerated step-up” approach. Initiating intravenous infliximab from diagnosis yielded greater clinical benefits, with an incremental gain of 0.17 QALYs per patient over a 5-year period, and was less costly, saving £1,681 per patient over the same time frame. Similar clinical benefits were obtained when modelling use of SC infliximab and adalimumab. The greatest cost savings were with adalimumab, totalling £10,059 per patient over 5 years. Sensitivity analyses further supported the robustness of the results for “top-down” therapy, showing it to be the most cost-effective option in 98.7% of model simulations.

Conclusion

This health economic analysis demonstrates that early effective “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. These findings were demonstrated for intravenous infliximab, subcutaneous infliximab and subcutaneous adalimumab. In newly-diagnosed patients with active Crohn’s disease, “top-down” treatment with anti-TNF therapy is more efficacious, safer and cost-effective than “accelerated step-up” based treatment strategies.

References

Noor NM, Lee JC, Bond S 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.

Disclosure

NMN declares educational/travel grants and/or speaker fees from AbbVie, Bristol Myers Squibb, Celltrion, Dr Falk Pharma, Ferring, Galapagos, J&J, Lilly, Pfizer, Pharmacosmos, Takeda and Tillotts Pharma AG.

Introduction

Esophageal varices (EV) are a critical complication of portal hypertension in patients with cirrhosis, and early detection is essential to prevent potentially life-threatening hemorrhage. The Baveno VII consensus recommends performing endoscopy in patients with transient elastography (TE) values exceeding 20 kPa and platelet counts below 150,000/mm³. While endoscopy remains the gold standard for diagnosis, non-invasive tests are gaining importance as a promising alternative for predicting EV(1) .The objective of our study is to predict the grade of varices in cirrhotic patients using a score derived from both their biological blood test results and clinical parameters.

Aims & Methods

The objective of our study was to predict the grade of varices in cirrhotic patients using a score derived from their biological blood test results and clinical parameters. This retrospective study involved patients recruited from Hôtel-Dieu de France, with data collected a few months prior to their gastroscopy for esophageal varices detection.
We calculated the ALBI-PLT score based on the method described by Inoue-Yuri et al.(2). The modified ALBI-PLT (mALBI-PLT) score was derived from the mALBI grade, assigning 1 point for grades 1 or 2a, and 2 points for grades 2b or 3. It also incorporated platelet counts, awarding 1 point for counts greater than 150,000/μL and 2 points for counts of 150,000/μL or lower. In addition to the mALBI-PLT score, we considered various variables, including blood test results and established predictive scores such as Child-Pugh, MELD-Na, FIB-4, and APRI.

Results

This study analyzed 108 cirrhotic patients (mean age: 63.94 years, 64.8% men, 33.03% had hepatocellular carcinoma (HCC)) out of 115 recruited, excluding cases with missing data. Key predictors of varice grades included lymphocyte count (L, β = −0.43, p = 0.011) and sodium (Na^10, β = −3.22 × 10^−22, p = 0.005) as significant negative associations. Positive associations were observed for the modified ALBI-platelet score (β = 0.43, p < 0.001), HCC (β = 0.51, p = 0.005), and gastrointestinal (GI) bleeding (β = 0.48, p = 0.013).
A derived formula for predicting varice grades is: VariceGrade = 3.49 − 0.43×ln(L) + 0.43×mALBI-PLT score − 3.22×10^−22×Na^10 + 0.51×HCC + 0.48×GI Bleeding.
The model showed strong specificity (94.5%) for identifying varices when the score was ≥ 1 and high sensitivity (97.8%) for excluding grade 3 varices when the score was ≤ 2.

Conclusion

This study introduces a non-invasive scoring system to accurately stratify esophageal varices severity, optimizing clinical decision-making and endoscopic screening in cirrhotic patients.

References

(1) de Franchis R, Bosch J, Garcia-Tsao G, Reiberger T, Ripoll C, Baveno VII Faculty. Baveno VII—Renewing consensus in portal hypertension. J Hepatol. 2022;76:959–974. doi: 10.1016/j.jhep.2021.12.022.
(2) Inoue-Yuri M, Enomoto H, Wakabayashi I, Yuri Y, Aizawa N, Ikeda N, Takashima T, Fujiwara A, Yoshioka R, Kawata S, Yoshihara K, Ota S, Nakano R, Shiomi H, Nishimura T, Nishiguchi S, Iijima H. Modification of the ALBI-PLT Score for the Prediction of High-risk Varices. In Vivo. 2022 May-Jun;36(3):1360-1366. doi: 10.21873/invivo.12839. PMID: 35478164; PMCID: PMC9087093.