Quality of Life is Improved and Kidney Function Preserved in Patients with Nephropathic Cystinosis Treated for 2 Years with Delayed-Release Cysteamine Bitartrate

• Type of Material: Article
• Authors: Craig B. Langman, Northwestern University; Larry Greenbaum, Emory University; Paul Grimm, Stanford University; Minnie Sarwal, Stanford University; Patrick Niaudet, Hôpital Necker Enfants Malades; Georges Deschenes, Hôpital Robert Debré; Elisabeth A. M. Cornelissen, Radboud University Nijmegen; Denis Morin, CHU Montpellier; Pierre Cochat, CHU Lyon; Ewa Elenberg, Baylor College of Medicine; Christian Hanna, Northwestern University; Segolene Gaillard, INSERM; Mary Jo Bagger, Raptor Pharmaceutical Inc.; Patrice Rioux, Raptor Pharmaceutical Inc.
• Language: English
• Date: 2014-09-01
• Publisher: Elsevier: 12 months
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: Copyright © 2014 Elsevier Inc. All rights reserved.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.jpeds.2014.05.013
• Title of Journal or Parent Work: Journal of Pediatrics
• ISSN: 0022-3476
• Volume: 165
• Issue: 3
• Start Page: 528
• End Page: +
• Grant/Funding Information: M.B. and P.R. are employees of Raptor Pharmaceuticals Inc.; Raptor Pharmaceuticals also supported the patients’ travel during the study.; Supported by Raptor Pharmaceuticals Inc.; and National Center for Advancing Translational Sciences of the National Institutes of Health (UL1TR000150, UL1TR000454, and UL1 TR000093).
• Keywords: ADULTS; Science & Technology; Pediatrics; THERAPY; Life Sciences & Biomedicine
• Research Categories: Health Sciences, Medicine and Surgery

Abstract

Objectives: To determine the long-term effects of delayed-release cysteamine bitartrate (DR-CYS) based on our previous work that established the short-term noninferiority of DR-CYS every 12 hours compared with immediate-release cysteamine bitartrate every 6 hours. Study design: We conducted a prospective, controlled, open label, single-arm study of DR-CYS for 2 years in 40 patients to assess efficacy in depletion of cystine in peripheral white blood cells, to assess the dose required to maintain white blood cell content of cystine <1 nmol cystine/mg protein, to measure quality of life using the Pediatric Quality of Life Inventory, change in estimated glomerular filtration rate, and change in height Z-score. Results: Through 24 months of study, the mean white blood cell content of cystine was always <1 nmol cystine/mg protein, and the dose of DR-CYS decreased from 43.5-40.1 mg/kg/d (P =.05), and the significant improvement in social function, school function, and in total function scores on the Pediatric Quality of Life Inventory remained. The estimated glomerular filtration rate was maintained and growth velocity was maintained at 24 months compared with the baseline height Z-score. Conclusions: The use of a DR-CYS administered every 12 hours to patients with cystinosis is of great benefit to their quality of life and to important biomarkers of disease control, when studied in a prospective, controlled fashion. We suggest that DR-CYS should be considered for substrate depletion in patients with cystinosis.