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. 2025 Mar 18;20(1):133.
doi: 10.1186/s13023-025-03658-8.

Development of the natural history component of an early economic model for primary sclerosing cholangitis

Christopher Bowlus  1 , Cynthia Levy  2 , Kris V Kowdley  3 , Nandita Kachru  4 , Sushanth Jeyakumar  5 , Yael Rodriguez-Guadarrama  5 , Nathaniel Smith  5 , Andrew Briggs  6 , Mark Sculpher  7 , Daniel Ollendorf  8
Affiliations

Development of the natural history component of an early economic model for primary sclerosing cholangitis

Christopher Bowlus et al. Orphanet J Rare Dis. .

Abstract

Background: Primary sclerosing cholangitis (PSC) is a rare, chronic cholestatic disease that can progress to cirrhosis and liver failure. The natural history of PSC is variable as liver enzymes and liver symptoms fluctuate over time. Several drugs for PSC are under investigation, but there are currently no economic models to evaluate the cost-effectiveness and value of new treatments. The objective of this study was to develop an early economic model for PSC and validate the natural history component.

Methods: A lifetime horizon Markov cohort model was developed to track the progression of adults with PSC with or without inflammatory bowel disease. Based on relevant literature and clinical expert advice, fibrosis staging was used to model disease progression. Evidence on disease progression, mortality, PSC-related complications, and secondary cancers was identified by literature searches and validated by interviews with clinical and cost-effectiveness modelling experts. Model outcomes were overall survival and transplant-free survival years, and the proportions of patients receiving liver transplants, 2nd liver transplants after recurrent PSC (rPSC), and developing rPSC after liver transplantation during their lifetime. Cumulative incidence of secondary cancers and quality-adjusted life-years (QALYs) were also tracked.

Results: Model outcomes are in line with estimates reported in literature recommended by clinical experts. Overall survival (95% uncertainty interval [UI]) was estimated to be 25.0 (23.2-26.3) years and transplant-free survival was estimated to be 22.0 (20.2-23.6) years. The estimated proportion (95% UI) of patients receiving first liver transplants was 14.5% (11.6-17.1%), while the proportion of patients developing rPSC and receiving 2nd liver transplants after rPSC was 24.2% (20.4-28.0%) and 21.6% (12.9-29.7%), respectively. The cumulative incidence (95% UI) of cholangiocarcinoma, colorectal cancer, and gallbladder cancer were estimated at 5.2% (2.1-10.0%), 3.6% (1.4-5.4%), and 3.3% (1.2-7.6%), respectively. Discounted lifetime QALYs per patient (95% UI) were estimated at 16.4 (15.6-17.1).

Conclusions: We have developed a model framework to simulate the progression of PSC with estimates of overall and transplant-free survival. This model, which calibrates well with existing estimates of disease progression, may be useful to evaluate the clinical and economic benefits of future treatments.

Keywords: Economic; Model; Natural history; Primary sclerosing cholangitis; Progression; Survival.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: CB has received grant funding and advisor fees from CymaBay Therapeutics, GSK, and Ipsen Bioscience; and has received grant funding from Boston Scientific, Calliditas Therapeutics, Cara Therapeutics, Chemomab, COUR Pharmaceuticals, Gilead Sciences, Hanmi Pharmaceuticals, Intercept Pharmaceuticals, Mirum Pharmaceuticals, Novo Nordisk, Pliant Therapeutics, and Viking Therapeutics; and has received advisor fees from Invea Therapeutics. CL has received grant funding and consultant fees from Calliditas Therapeutics, CymaBay Therapeutics, Gilead Sciences, GSK, Intercept Pharmaceuticals, Ipsen Bioscience, and Pliant Therapeutics; and has received grant funding from Cara Therapeutics, Escient Pharmaceuticals, GENFIT, HighTide Therapeutics, Mirum Pharmaceuticals, Novartis, and Zydus Lifesciences. KVK has received grant funding and consultant fees from CymaBay Therapeutics, GENFIT, Gilead Sciences, Intercept Pharmaceuticals, Madrigal Pharmaceuticals, Mirum Pharmaceuticals, NGM Biopharmaceuticals, Pfizer, and 89Bio; has received consultant fees from Enanta Pharmaceuticals, HighTide Therapeutics, and Inipharm; has received grant funding from Corcept Therapeutics, GSK, Hanmi Pharmaceutical, Novo Nordisk, Pliant Therapeutics, Terns Pharmaceuticals, and Viking Therapeutics; has received speaker bureau honoraria from AbbVie, Gilead Sciences, and Intercept Pharmaceuticals; and has stock options with Inipharm. NK is an employee of, and has stock options with, Gilead Sciences. SJ, YR, and NS are employees of Maple Health Group who conducted/executed the study on behalf of Gilead Sciences and were paid by Gilead Sciences for their services. AB and MS have received consultant fees from Gilead Sciences. DO has received consultant fees from Gilead Sciences and is employed at a research center that accepts sponsorship funding for its databases from life sciences companies, government agencies, and academic institutions.

Figures

Fig. 1
Fig. 1
Modeled progression of disease. IBD, inflammatory bowel disease; PSC, primary sclerosing cholangitis
Fig. 2
Fig. 2
Sensitivity analysis of overall survival. (A) Probabilistic sensitivity analysis and (B) one-way sensitivity analysis. CC, compensated cirrhosis; CCA, cholangiocarcinoma; CRC, colorectal cancer; DCC, decompensated cirrhosis; GBC, gallbladder cancer; HCC, hepatocellular carcinoma; IBD, inflammatory bowel disease; LT, liver transplant; PLT, post-liver transplant; PSC, primary sclerosing cholangitis; rPSC, reemergent PSC; TP, transition probability; UI, uncertainty interval
Fig. 3
Fig. 3
Sensitivity analysis of discounted quality-adjusted life years. (A) Probabilistic sensitivity analysis and (B) one-way sensitivity analysis. CC, compensated cirrhosis; CCA, cholangiocarcinoma; CRC, colorectal cancer; DCC, decompensated cirrhosis; GBC, gallbladder cancer; HCC, hepatocellular carcinoma; IBD, inflammatory bowel disease; LT, liver transplant; PLT, post-liver transplant; PSC, primary sclerosing cholangitis; rPSC, reemergent PSC; QALY, quality-adjusted life years; TP, transition probability; UI, uncertainty interval
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