ESPN 54th Annual Meeting

ESPN 2022


 
Effects of transitioning from immediate release to extended release cysteamine therapy in Norwegian patients with nephropathic cystinosis
SONJA AMDAL AASE 1 MARIA RADTKE 2 CHRISTIAN SIVA 3 BJøRN EGIL VIKSE 4 DAMIEN BRACKMAN 5 HELGA GUDMUNDSDOTTIR 6 BRITA FORSBERG 7 ANNA BJERRE 8

1- STAVANGER UNIVERSITY HOSPITAL
2- ST:OLAVS UNIVERSITY HOSPITAL
3- VESTFOLD HOSPITAL
4- HAUGESUND HOSPITAL
5- HAUKELAND UNIVERSITY HOSPITAL
6- ULLEVåL UNIVERSITY HOSPITAL
7- CHIESI GLOBAL RARE DISEASES, NORDICS
8- OSLO UNIVERSITY HOSPITAL
 
Introduction:

Nephropathic cystinosis is a rare lysosomal storage disorder where accumulation of cystine, and formation of crystals, progressively damages various organs, including kidneys, retina, muscles and central nervous system. 
Cysteamine has been available since 1997 as immediate release (IR) formulation, Cystagon®, and since 2013 as extended release (ER) formulation, Procysbi®. The 10 Norwegian patients were all switched from IR- to ER-cysteamine in 2015-2016.
The aim of this long-term, retrospective study was to evaluate implementation of ER-cysteamine in patients already treated with IR-cysteamine. Primary efficacy endpoints were white blood cell (WBC) cystine levels and estimated glomerular filtration rate (eGFR) change per year.

Material and methods:

All 10 Norwegian paediatric- and adult patients participated in the study and data were obtained retrospectively from up to 6 years prior to the switch, until time of inclusion.

Results:

Mean level of WBC cystine remained stable between the IR- and ER treatment periods (1.19 versus 1.38 nmol hemicystine/mg protein) despite a dose reduction in most patients on ER-treatment.
Mean eGFR change per year was more pronounced during ER-treatment compared to during IR-treament (-4.41 versus -0.17 ml/min/1.73m2/year). However, single events, such as tubulointerstitial nephritis and kidney transplantation, could have influenced the results.
Z-height score developed positively from -1.062 before switch to -0.330 after switch.
Four of seven patients with halitosis, reported improvement of symptoms after switch, one reported unchanged symptoms and two reported worsened symptoms.
Most adverse drug reactions (ADRs) were of mild to moderate severity during both periods. However, one patient developed two serious ADRs during ER-treatment and was eventually switched back to IR-formulation.

Conclusions:

The results from this long-term retrospective study indicates that a switch from IR- to ER-cysteamine was feasible and safe under routine clinical practice. However, due to the low number of patients, and the retrospective collection of data, it is hard to draw any definitive conclusions.