Abstract
Aim:
Alagille syndrome (ALGS) is a rare genetic disorder associated with cholestasis and subsequent severe pruritus, which significantly impacts patient quality of life (QoL). Odevixibat (ODX) and maralixibat (MRX) are ileal bile acid transporter inhibitors approved for the treatment of cholestatic pruritus in ALGS. In the absence of head-to-head data, this study aimed to compare the efficacy, safety, and health-related QoL (HRQoL) associated with ODX and MRX.
Materials & methods:
A population-adjusted unanchored indirect treatment comparison was conducted using patient-level data from the Phase III ASSERT/ASSERT-EXT studies (ODX) and published data from the Phase IIb ICONIC study (MRX). A regression-adjusted matching approach was applied to adjust for cross-trial differences in baseline characteristics and estimate treatment effects. Outcomes assessed at week 48 included pruritus, serum bile acid (sBA) levels, HRQoL (PedsQL) and safety.
Results:
In adjusted analyses, ODX demonstrated numerically greater improvements in pruritus and reductions in sBA than MRX. ODX was associated with significantly greater improvements in HRQoL, including overall PedsQL scores (mean difference: 14.64; 95% CI: 5.70–23.58). ODX was better tolerated, with significantly lower rates of gastrointestinal adverse events (odds ratio [OR]: 0.22; 95% CI: 0.06–0.87) and abdominal pain (OR: 0.06; 95% CI: 0–0.83), and numerically lower rates of other adverse events.
Conclusion:
In this first indirect treatment comparison of ileal bile acid transporter inhibitors in ALGS, ODX demonstrated a differentiated clinical profile versus MRX, with significant benefits in HRQoL and tolerability, and consistent trends favoring better efficacy. These results may support informed treatment decision-making for patients.