Maralixibat Treatment Response in Alagille Syndrome is Associated with Improved Health-Related Quality of Life

• Published in: The Journal of pediatrics 2023-01, Vol.252, p.68-75.e5
• Main Authors: Kamath, Binita M., Goldstein, Andrea, Howard, Robin, Garner, Will, Vig, Pamela, Marden, Jessica R., Billmyer, Emma, Anderson, Annika, Kirson, Noam, Jacquemin, Emmanuel, Gonzales, Emmanuel
• Format: Article
• Language: English
• Subjects: Alagille Syndrome - drug therapy; Child; cholestasis; family impact; fatigue; Fatigue - drug therapy; Fatigue - etiology; HRQoL; Humans; ileal bile acid transporter; liver disease; pediatric; PedsQL; Pruritus - drug therapy; Pruritus - etiology; Quality of Life; rare disease; serum bile acids
• ISSN: 0022-3476; 1097-6833
• DOI: 10.1016/j.jpeds.2022.09.001

The objective of this study was 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. 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 Alagille syndrome with moderate-to-severe pruritus. Clinically meaningful treatment response to maralixibat was defined a priori as a ≥1-point reduction in the Itch-Reported Outcome (Observer) score, from baseline to week 48. HRQoL was assessed using the Pediatric Quality of Life Inventory Generic Core, Family Impact, and Multidimensional Fatigue scale scores, which were collected via the caregiver. The minimal clinically important difference for HRQoL ranged from 4 to 5 points, depending on the scale. Twenty of the 27 patients (74%) included in this analysis achieved an Itch-Reported Outcome (Observer) treatment response at week 48. The mean (SD) change in Multidimensional Fatigue score was +25.8 (23.0) for responders vs −3.1 (19.8) for nonresponders (P = .03). Smaller and non-statistically significant mean changes were observed for the Pediatric Quality of Life Inventory Generic Core and Family Impact scores. Controlling for baseline Family Impact score, responders’ Family Impact 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 Pediatric Quality of Life Inventory Generic Core and Multidimensional Fatigue scores. The significant improvements in pruritus seen with maralixibat at week 48 of the ICONIC study are clinically meaningful and are associated with improved HRQoL. ClinicalTrials.gov: NCT02160782.