Abstract

Objective: (s): To assess the impact of treatment response to the ileal bile acid transporter inhibitor maralixibat on health-related quality of life (HRQoL) in children with Alagille syndrome ( ALGS).

Study design: This analysis used data from the ICONIC trial, a Phase 2 study with a 4-week double-blind, placebo-controlled, randomized drug withdrawal period in children with ALGS with moderate-to-severe pruritus. Clinically meaningful treatment response to maralixibat was defined a priori as a ≥1-point reduction in Itch-Reported Outcome (Observer) (ItchRO[Obs]) score, from baseline to week 48. HRQoL was assessed using the Pediatric Quality of Life Inventory Generic Core (PedsQL), Family Impact (FI), and Multidimensional Fatigue (MF) scale scores, which were collected via caregiver. The minimal clinically important difference for HRQoL ranged from 4 to 5 points, depending on the scale.

Results: Twenty of the 27 patients (74%) included in this analysis achieved an ItchRO(Obs) treatment response at week 48. The mean (standard deviation) change in MF Score was +25.8 (23.0) for responders versus -3.1 (19.8) for non-responders (P = .03). Smaller and non-statistically significant mean changes were observed for the PedsQL and FI scores. Controlling for baseline FI Score, responders' FI scores increased an average of 16.9 points over 48 weeks compared with non-responders (P = .05). Smaller and non-statistically significant point estimates were observed for the PedsQL and MF scores.

Conclusion: (s): The significant improvements in pruritus seen with maralixibat at week 48 of the ICONIC study are clinically meaningful and are associated with improved HRQoL.