Unraveling the Relationship Between Itching, Scratch Scales, and Biomarkers in Children With Alagille Syndrome

• Type of Material: Article
• Authors: Binita M. Kamath, University of Toronto; Cathie Spino, University of Michigan; Richard McLain, University of Michigan; John C. Magee, University of Michigan; Emily M. Fredericks, University of Michigan; Kenneth D. Setchell, Cincinnati Childrens Hospital Medical Center; Alexander Miethke, Cincinnati Childrens Hospital Medical Center; Jean P. Molleston, Indiana University; Cara L. Mack, University of Colorado; Robert H. Squires, UPMC Childrens Hospital Pittsburgh; Estella M. Alonso, Northwestern University; Karen F. Murray, University of Washington; Kathleen M. Loomes, University of Pennsylvania; M. Kyle Jensen, University of Utah; Saul Karpen, Emory University; Philip Rosenthal, University of California San Francisco; Danny Thomas, Childrens Hospital Los Angeles; Ronald J. Sokol, University of Colorado; Benjamin L. Shneider, Baylor College of Medicine
• Language: English
• Date: 2020-05-26
• Publisher: Wiley Periodicals, Inc.
• Publication Version: Final Published Version
• Copyright Statement: © 2020 The Authors.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1002/hep4.1522
• Title of Journal or Parent Work: Hepatology Communications
• Volume: 4
• Issue: 7
• Start Page: 1012
• End Page: 1018
• Grant/Funding Information: and the National Center for Advancing Translational Sciences (UL1 RR025014, UL1 TR000423, UL1 TR001857, UL1 TR001872, UL1 TR001878, UL1 TR002535, UL1TR00130, and UL1TR002378).; Financial Support: National Institute of Diabetes and Digestive and Kidney Diseases (DK 62436, DK 62445, DK 62453, DK 62456, DK 62466, DK 62470, DK 62481, DK 62497, DK 62500, DK 84536, DK 84538, DK 84575, DK103135, DK103140, and DK103149)
• Keywords: Bile; Reliability; Quality of life; Gastroenterology & Hepatology; Life Sciences & Biomedicine; PEDSQL(TM)-4.0; Atopic dermatitis; Science & Technology; Pruritus; Impact
• Research Categories: Health Sciences, Human Development; Health Sciences, Public Health; Health Sciences, Pathology

Abstract

Pruritus is a debilitating symptom for patients with Alagille syndrome (ALGS). In a previously reported trial of maralixibat, an investigational antipruritic agent, itching was assessed using a digital diary based on twice-daily caregiver observation of itching severity (Itch Reported Outcome, ItchRO[Observer]). The goal of this study was to characterize pruritus in participants with ALGS at baseline in this trial, as assessed by the ItchRO instrument and the physician-observed clinician scratch scale (CSS), relative to biomarkers putatively associated with pruritus and health-related quality of life assessment. Thirty-seven participants with ALGS (median age of 6 years; range 1-17 years) were enrolled. No association was identified between CSS and ItchRO(Obs) (r = 0.22, P = 0.2). Neither CSS nor ItchRO were associated with serum bile acids (r = -0.08, P = 0.6 for both) or autotaxin (r = 0.22, P = 0.2; r = 0.28, P = 0.12). There was no significant association between Pediatric Quality of Life Inventory total parent scores and CSS or ItchRO (r = -0.23, P = 0.2; r = -0.16, P = 0.36). There was a significant association between ItchRO and Multidimensional Fatigue Scale and Family Impact Module total scores (Pearson correlation coefficient -0.575, P = 0.0005; 0.504, P = 0.002). In exploratory analysis, selected questions relating to fatigue and sleep disturbance (n = 12) from Pediatric Quality of Life Inventory, Multidimensional Fatigue Scale, and Family Impact Module were correlated with pruritus scores; positive associations were identified. Conclusion: Itching scores did not correlate with each other, nor with putative serum biomarkers of pruritus, and further, did not correlate with quality of life. Hypothesis-generating analyses implicate sleep disturbance and fatigue as key associations with caregiver observations of itching. This is highly relevant to the selection of surrogate endpoints for clinical trials of pruritus therapies.