Alagille Syndrome

Funded multicenter natural history studies are valuable in Alagille syndrome

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Long-term conventional randomized clinical trials are hard to conduct in rare diseases leading to issues related to evidenced-based drug development. Use of real-world data to assess new therapies is a growing trend in this area.

To determine the use of funded multicenter prospective longitudinal databases to inform evolving clinical trials of intestinal bile acid transport inhibitors in Alagille syndrome (ALGS), researchers applied inclusion and exclusion criteria from a published trial of maralixibat (ITCH) to a prospective longitudinal cohort of children with cholestasis (LOGIC NCT00571272).

From the 252 participants with ALGS who had their native liver in LOGIC, 59 met adapted inclusion and exclusion criteria of ITCH.

A cohort was yielded using frequency weighting to match the age distribution of ITCH. The cohort (Alagille Syndrome Natural History [ALGS NH]) was similar to the baseline status of participants in ITCH.

There was a significant reduction in pruritus in the weighted ALGS NH cohort during the 2-year prospective follow-up. Total bilirubin, albumin, and alanine aminotransferase levels remained unchanged during the same 2-year period. Platelet count however dropped significantly.

At 2 years, weighted survival with native liver was 91% in the ALGS NH.

“These investigations provide valuable real-world data that can serve as contextual comparators to current clinical trials, especially those without control populations, and highlight the value and importance of funded multicenter, prospective, natural history studies,” the authors concluded.


Shneider BL, Kamath BM, Magee JC, et al; Childhood Liver Disease Research Network (ChiLDReN). Use of funded multicenter prospective longitudinal databases to inform clinical trials in rare diseases-Examination of cholestatic liver disease in Alagille syndrome. Hepatol Commun. 2022;doi: 10.1002/hep4.1970. Epub ahead of print. PMID: 35506349.


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