The burden of Alagille syndrome: uncovering the potential of emerging therapeutics – a comprehensive systematic literature review
Publication: Journal of Comparative Effectiveness Research
Abstract
Aim: Alagille syndrome (ALGS) is a rare, cholestatic multiorgan disease associated with bile duct paucity, leading to cholestasis. Clinical symptoms of cholestasis include debilitating pruritus, xanthomas, fat-soluble vitamin deficiencies, growth failure, renal disease and impaired health-related quality of life (HRQoL). The main objective was to review the current literature on the epidemiological, clinical, psychosocial and economic burden of ALGS in view of the development of ileal bile acid transporter (IBAT) inhibitors. Methods: Electronic literature databases were searched in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist. Results: 330 publications were screened, 119 were relevant: 11 randomized controlled trials (RCTs), 21 non-RCTs, 10 HRQoL studies, two studies assessing cost/resource use and 77 epidemiological studies across several databases through 31 July 2024. Studies confirm that patients with ALGS experience cardiac anomalies, impaired growth, renal disease, poor HRQoL, fat-soluble vitamin deficiencies and debilitating pruritus; until the approval of IBAT inhibitors for the treatment of cholestatic pruritus in patients with ALGS, supportive management was the standard of care. Conclusion: This review confirms the substantial clinical, economic and HRQoL burden associated with ALGS and consolidates current treatment evidence. Data from recent trials in ALGS demonstrate the potential impact of IBAT inhibitors to transform lives by improving cholestatic pruritus symptoms, HRQoL and native liver survival.
Plain language summary: understanding the impact of Alagille syndrome and the promise of new treatments
What is this article about?
This article is about Alagille syndrome (ALGS), a rare disease that affects multiple organs and leads to bile duct problems, causing symptoms like severe itching, poor growth, kidney disease, vitamin deficiencies and low quality of life. The main goal of the review was to examine the impact of ALGS on patients' health and well-being and consider how a new treatment class, called ileal bile acid transporter (IBAT) inhibitors, could help.
What were the results?
The researchers reviewed 330 publications, which were narrowed down to 119 relevant studies. These included clinical trials, quality of life studies and cost/resource studies. The findings confirm that people with ALGS experience a range of serious issues, including heart problems, poor growth, kidney disease and debilitating itching. Before the approval of IBAT inhibitors, treatment mainly focused on managing symptoms.
What do the results of the study mean?
The review concludes that ALGS causes significant health, economic and quality of life challenges for patients. However, recent research shows that IBAT inhibitors could dramatically improve symptoms like itching, overall quality of life and liver health in these patients, offering hope for better management of the disease.
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Received: 30 September 2024
Accepted: 17 December 2024
Published online: 14 January 2025
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The burden of Alagille syndrome: uncovering the potential of emerging therapeutics – a comprehensive systematic literature review. (2025) Journal of Comparative Effectiveness Research. DOI: 10.57264/cer-2024-0188
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