Supplementary materials: The burden of Alagille syndrome: uncovering the potential of emerging therapeutics – a comprehensive systematic literature review
These are peer-reviewed supplementary materials for the article 'Indirect treatment comparison of lanadelumab and a C1-esterase inhibitor in pediatric patients with hereditary angioedema' published in the Journal of Comparative Effectiveness Research.
- Appendix A: Review questions
- Appendix B: Search strategy
- Appendix C: Data extraction and quality assessment
- Appendix D: Selection criteria
- Table 1: Selection criteria to be used for Review Question 1 (RCTs).
- Table 2: Selection criteria to be used for Review Question 2 (non-RCTs).
- Table 3: Selection criteria to be used for Review Question 3 (cost-effectiveness studies).
- Table 4: Selection criteria to be used for Review Question 4 (HRQoL studies).
- Table 5: Selection criteria to be used for Review Question 5 (cost and resource use studies).
- Table 6: Selection criteria to be used for Review Question 6 (burden studies).
- Appendix E: Summary table of clinical studies and their outcomes
- Table 8: Summary of all clinical studies included in the literature review.
- Table 9: Endpoint results in clinical studies.
- Appendix F: PRISMA diagram
- Figure 1: PRISMA diagram
- References
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, fatsoluble 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.