Quality of life is improved and kidney function preserved in patients with nephropathic cystinosis treated for 2 years with delayed-release cysteamine bitartrate

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 ½ 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 ½ 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.

Trial registration: ClinicalTrials.gov NCT01197378.

Conflict of interest statement

The other authors declare no conflicts of interest.

Copyright © 2014 The Authors. Published by Mosby, Inc. All rights reserved.

Figures

Figure 1

A, Mean WBC (cystine) remained below 1 nmol ½ cystine/mg protein during the entire study. The solid line denotes the optimal upper level of WBC (cystine) to be achieved during substrate reduction therapy with cysteamine. There was no significant change in the WBC (cystine) over the 24-month study. B, The total daily dose (mg/kg/day) of DR-CYS in the study population over the study was reduced significantly. The box plots below show the median (−), mean (♦), and the first and third quartiles denoted by the upper and lower ends of the box, respectively. The lower and upper whiskers denote the minimum and maximum, respectively, and the (○) represent the outliers. The mean dose was reduced from 43.5 to 40.1 mg/kg/d, P = .05, during the 24-month study.

Figure 2

WBC (cystine) vs plasma (cysteamine) for all study patients who had a WBC (cystine) ≤1 nmol/1/2 cystine/mg protein; 94.5% of measured plasma (cysteamine) values were >0.1 mg/dL when the WBC (cystine) was ≤1 nmol ½ cystine/mg protein.

Figure 3

A, Evolution of height (Z-score) over the 24-month study. There was no significant change in height Z-socre during the 24-month study. B, The eGFR of the study population over time. The box plots below show the median (−), mean (♦), and the first and third quartiles denoted by the upper and lower ends of the box, respectively. The lower and upper whiskers denote the minimum and maximum, respectively, and the (○) represent the outliers. The mean eGFR did not decline significantly during the course of the 24-month study.