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.

The renal Fanconi syndrome in cystinosis: pathogenic insights and therapeutic perspectives

“…162). Although this new formulation needs to be taken only every 12 h, thus improving the quality-of-life of affected patients 163,164 , the impact on the disease is expected to be similar, in delaying but not arresting the complications. Topical cysteamine hydrochloride eye drops are highly effective in reducing the density of corneal crystals and alleviating the associated symptoms 7,165 .…”

Orphan drug policies and use in pediatric nephrology

“…This preparation requires administration every 6 h and has considerable gastrointestinal side effects [31]. A delayed-release preparation (Procysbi) given every 12 h within enteric-coated spheres reduced the side effects and improved quality of life, and thereby compliance to administration regimens [32]. Procysbi's annual price tag per patient is approximately $250,000 compared to $10,000/ year for Cystagon.…”

Protein misfolding diseases: Prospects of pharmacological treatment

“…A curcumin derivative, BCM95, along with an autophagy inducer, hydroxypropyl‐β‐cyclodextrin, may also be effective in the treatment of saposin C deficiency via the improvement of lysosome function . Finally, autophagy inducers have been proven of potential use via the treatment of cystinosis with cysteamine …”

“…111 Finally, autophagy inducers have been proven of potential use via the treatment of cystinosis with cysteamine. 112 In total, around 40 PCs have been described as effective in the treatment of different IEMs, most of them for LSDs, 12,45 but of these only few are used clinically or are under pharmaceutical development (Table 1).…”