Division of Gastroenterology, Hepatology and Nutrition, The Hospital for Sick Children and University of Toronto, Toronto, Canada.
Mirum Pharmaceuticals, Inc., Foster City, CA.
J Pediatr. 2023 Jan;252:68-75.e5. doi: 10.1016/j.jpeds.2022.09.001. Epub 2022 Sep 10.
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.
本研究旨在评估回肠胆酸转运蛋白抑制剂马拉利昔巴特（maralixibat）治疗应答对 Alagille 综合征患儿健康相关生活质量（HRQoL）的影响。
本分析使用了 ICONIC 试验的数据，这是一项针对中重度瘙痒的 Alagille 综合征患儿进行的为期 4 周的双盲、安慰剂对照、随机药物撤药期的 2 期研究。maralixibat 治疗应答的临床显著定义为瘙痒报告结局（观察者）评分从基线到第 48 周至少下降 1 分。HRQoL 通过 caregiver报告的儿童生活质量量表通用核心、家庭影响和多维疲劳量表评分进行评估。HRQoL 的最小临床重要差异范围为 4-5 分，具体取决于量表。
本分析纳入的 27 例患者中有 20 例（74%）在第 48 周达到了瘙痒报告结局（观察者）治疗应答。应答者的多维疲劳评分平均（SD）变化为+25.8（23.0），而非应答者为-3.1（19.8）（P=.03）。对于儿童生活质量量表通用核心和家庭影响评分，观察到更小且无统计学意义的平均变化。控制基线家庭影响评分后，与非应答者相比，应答者的家庭影响评分在 48 周内平均增加 16.9 分（P=.05）。对于儿童生活质量量表通用核心和多维疲劳评分，观察到更小且无统计学意义的点估计。
ICONIC 研究中第 48 周马拉利昔巴特治疗瘙痒的显著改善具有临床意义，并与 HRQoL 的改善相关。
ClinicalTrials.gov：NCT02160782。
