Journal Article

OC45 Maralixibat improves growth in patients with alagille syndrome: a 4-year analysis

Kamath, B M, Baek, M, Nunes, T, Mogul, D B, Vig, P

2023

Overview

Maralixibat (MRX) is an ileal bile acid transporter inhibitor (IBATi) recently approved by the Food and Drug Administration for the treatment of cholestatic pruritus in patients with Alagille syndrome (ALGS) 1 year of age and older. Recent data suggest that MRX is associated with improved event-free survival in this population suggesting that the drug may potentially improve liver disease outcomes beyond pruritus control in ALGS. Patients with ALGS clearly have impaired growth and therefore we evaluated the impact of long-term MRX treatment on the nutritional status of these patients.Height and weight Z-scores were evaluated in patients who participated in 3 clinical trials of MRX and their long-term, open-label extensions for treatment of cholestatic pruritus in ALGS; only patients for whom we had height and weight data at baseline and week 204 follow-up were included. T-tests and Pearson correlation coefficients were used to evaluate the association between height with other parameters known to correlate with growth.Data were available for 34 patients with baseline mean (SD) age of 6.7 (3.8) years, height Z-score of -1.66 (1.17) and weight Z-score of -1.46 (0.95). Overall, mean height Z-score increased to -1.29 (1.03) at week 204 (change from baseline: 0.37; p=0.0004). The greatest catch-up height gain was observed among those within the lowest baseline quartile height Z-scores, increasing from -3.1 (0.71) at baseline to -2.38 (0.82) at week 204 (change from baseline: 0.72; p=0.018), and there was a significant correlation between change in height and baseline height (r=-0.48; p=0.004). Similarly, greater catch-up weight gain was observed with lower baseline weight Z-scores, with a significant correlation between change in weight and baseline weight (r=-0.39; p=0.02). The change in height Z-scores correlated with the change in weight Z-scores such that greater catch-up linear growth was observed in patients with greater catch-up weight gain (r=0.73; p<0.0001). There was no clear change in vitamin D levels or albumin throughout treatment. Among patients with sBA <200 µmol/L at week 48, height Z-score increased from -1.58 (1.23) at baseline to -1.16 (1.00) at week 204 (change from baseline: 0.42; p=0.001), whereas there was no significant change in height Z-score among patients with sBA ≥200 µmol/L.Catch-up height and weight are observed in patients with ALGS treated with MRX, and importantly patients with the greatest height disadvantage at baseline had the greatest catch-up in height. Increased catch-up height was also seen in patients that achieved lower sBA with MRX, suggesting an improvement in bile acid homeostasis may be a factor. Further analyses are needed comparing growth trajectories in MRX-treated patients to a natural history cohort of patients with ALGS to fully understand the attributability of MRX.

• Publisher: BMJ Publishing Group LTD
• Subject: Pruritus