Natural history data may be helpful in assessing outcomes in ALGS
Using natural history data from prospective longitudinal databases may help determine the potential impact of investigational treatments on patients with Alagille Syndrome (ALGS), according to a study presented at The Liver Meeting 2021.
According to presenter, Benjamin Shneider, MD, prolonged treatment with placebo as a comparison is difficult in patients with cholestatic liver diseases. Shneider et al investigated whether determining outcomes in ALGS without investigational treatment was feasible by applying clinical trial-based selection criteria to a prospective longitudinal observational study.
Researchers used the eligibility criteria from a randomized trial of maralixibat in patients with ALGS (ITCH; CT02057692) on participants in the Longitudinal Study of Genetic Causes of Intrahepatic Cholestasis (LOGIC; NCT00571272). Frequency weighting was applied to the LOGIC cohort for analysis due to a higher number of participants < 2 years of age compared to the ITCH cohort.
There were 252 children with ALGS and their native liver enrolled in LOGIC, of which 59 were not enrolled in ITCH and met eligibility criteria with ≥1 follow up.
The weighted cohort was well-matched to the baseline ITCH cohort. Statistically and clinically significant reductions in pruritus were seen at 1- and 2-year follow-up.
At 1 year, there was a 59% reduction in clinician scratch scale and at 2 years, that increased to 73%. During this time there were no major changes in the use of anti-pruritic agents. After 2 years, 24% of the cohort had no scratching and 31% had mild scratching. Platelet count decreased significantly during the 2-year follow-up, while height, but not weight z-score, increased significantly during follow-up.
“This clinical data may be useful in contextualizing the findings of clinical trials,” the authors concluded.
Shneider B, et al. Utilization of Multi-Center Prospective Longitudinal Databases to Inform Clinical Trials in Rare Diseases- Examination of Cholestatic Liver Disease in Alagille syndrome (ALGS). Presented at: The Liver Meeting 2021.