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Adherence to cysteamine in nephropathic cystinosis: A unique electronic monitoring experience for a better understanding. A prospective cohort study: CrYSTobs

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Abstract

Introduction

In nephropathic cystinosis (NC), adherence to cysteamine remains challenging; poor adherence is worsening the disease progression with a decline of kidney function and increase of extrarenal morbidities. Our objective was to describe adherence to cysteamine in NC patients, using electronic monitoring systems.

Methods

Patients with confirmed NC, aged > 4 years and receiving oral cysteamine (short acting or delayed release formulation as standard of care) from 3 French reference centers, were included. Adherence to treatment was primarily assessed as the percentage of days with a good adherence score, adherence score rating from 0 (poor) to 2 (good). A descriptive analysis was performed after 1-year follow-up.

Results

Seventeen patients (10 girls, median age: 13.9 (5.4–33.0) years) were included. Median age at diagnosis was 17.0 (3.0–76.9) months and age at start of cysteamine was 21.0 (15.5–116.3) months. Median daily dose of cysteamine was 1.05 (0.55–1.63) g/m2/day. Over the year, the median percentage of days with a good adherence score was 80 (1–99)% decreasing to 68 (1–99)% in patients > 11 years old. The median of average number of hours covered by treatment in a day was 22.5 (6.1–23.9) versus 14.9 (9.2–20.5) hours for delayed release versus short acting cysteamine.

Conclusion

Our data are the first describing a rather good adherence to cysteamine, decreasing in adolescents and adults. We described a potential interest of the delayed release formulation. Our data highlight the need for a multidisciplinary approach including therapeutic education and individualized approaches in NC patients transitioning to adulthood.

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Abbreviations

ACD:

Acid citric citrate dextrose

AUC:

Area under the curve

BCA:

BiCinchoninic acid Assay

BSA:

Body surface area

CIC:

Clinical Investigation Center (Centre d’Investigation Clinique)

CKD:

Chronic kidney disease

CPP:

Comité de Protection des Personnes

CTNS:

Cystinosis gene

DR:

Delayed release

GFR:

Glomerular filtration rate

LC-MS/MS:

Liquid chromatography–tandem mass spectroscopy

MEMs:

Medication event monitoring system

NC:

Nephropathic cystinosis

ORKID:

Orphan Kidney Disease

SA:

Short acting

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Acknowledgements

We wish to thank the clinical investigation centers which participated in the recruitment and follow-up of the patients: CIC of Robert Debré (Dr Florentia Kaguelidou, Mr. François Luc,,Mrs. Christine Samy, Dr. Ying Wang and Mrs. Setareh Zarrabian), CIC of Montpellier (Mr Hugues Chevassus, Mrs. Mirna Khalil and Mrs. Cécile Rouge).

We also wish to thank the team in Lyon that participated actively in the preparation and conduct of the study:

  • Valentine Bréant and Bettina Colombet, hospital pharmacists;

  • Luc Anselmini, Florine Coeurdray, Aurélie Félizard, Delphine Grosjean, Flore Maillot, and Damien Thomas, lab technicians;

  • Nathalie Touil, neuropsychologist and Aurore Curie, neuropediatrician;

  • Christelle Bonifas and Jacques Fleury, ophthalmologists;

  • Béatrice Abel, Najet Belghali, Eleonore Brocard, Catherine Caire, Corine Di-Cara, and Mélanie Romier, study nurses;

  • And a very special thanks to the clinical research associates who greatly contributed to the quality of the data: Fanny Abad, Caroline Douchet, and Hanane Gheit.

We finally thank the patients’ organizations (Cystinose France, Vaincre les Maladies Lysosomales and Association pour l’Information et la Recherche sur les maladies Rénales Génétiques) and the patients who agreed to participate in this study and gave their time for this project.

Availability of data and material

Data can be shared following regulatory and confidentiality requirements to other researchers on request after thorough review of the objective.

Funding

This project was supported by a grant from the ministry of health through the “Programme Hospitalier de Recherche Clinique National” in 2009.

Author information

Authors and Affiliations

  1. Hospices Civils de Lyon, EPICIME-CIC 1407 de Lyon, Inserm, Department of Clinical Epidemiology, CHU-Lyon, F-69677, Bron, France

    Segolene Gaillard, Behrouz Kassai, Patrice Nony, Eurielle Bodénan & Valérie Laudy

  2. Université de Lyon, F-69000, Lyon, Université Lyon 1; CNRS, UMR 5558, Laboratoire de Biométrie et Biologie Evolutive, F-69622, Villeurbanne, France

    Segolene Gaillard, Laurent Roche, Behrouz Kassai, Patrice Nony, Valérie Laudy, Fabien Subtil & Catherine Mercier

  3. Service de Néphrologie, Dialyse, Hypertension artérielle, Hôpital Edouard Herriot, Hospices Civils de Lyon, Université de Lyon, Lyon, France

    Sandrine Lemoine

  4. Hospices Civils de Lyon, Service de Biostatistique, F-69324, Lyon, France

    Laurent Roche, Fabien Subtil & Catherine Mercier

  5. APHP, Hôpital Robert Debré, Service de néphrologie pédiatrique, Paris, France

    Georges Deschênes

  6. CHU Montpellier, Service de néphrologie et endocrinologie pédiatrique, Montpellier, France

    Denis Morin

  7. Hospices Civils de Lyon, Service Biochimie et Biologie Moléculaire, UF Maladies Héréditaires du Métabolisme, F-69500, Bron, France

    Christine Vianey-Saban & Cécile Acquaviva-Bourdain

  8. Hospices Civils de Lyon, Service de Néphrologie Pédiatrique, et centre de référence maladies rénales et phosphocalciques rares- Néphrogones- Filière ORKiD -69500, Bron, France

    Bruno Ranchin, Justine Bacchetta, Pierre Cochat & Aurélia Bertholet-Thomas

  9. CHU Montpellier, Centre d’Investigation Clinique, Inserm CIC 1411, F-69500, Bron, Montpellier, France

    Cécile Rouges

  10. Centre d’Investigation Clinique - CIC 1426 Hôpital Robert Debre - Assistance Publique - Hopitaux de Paris (AP-HP), Paris, France

    Setareh Zarrabian

Authors
  1. Segolene Gaillard
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  2. Laurent Roche
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  3. Sandrine Lemoine
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  4. Georges Deschênes
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  5. Denis Morin
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  6. Christine Vianey-Saban
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  7. Cécile Acquaviva-Bourdain
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  8. Bruno Ranchin
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  9. Justine Bacchetta
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  10. Behrouz Kassai
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  11. Patrice Nony
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  12. Eurielle Bodénan
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  13. Valérie Laudy
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  14. Cécile Rouges
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  15. Setareh Zarrabian
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  16. Fabien Subtil
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  17. Catherine Mercier
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  18. Pierre Cochat
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  19. Aurélia Bertholet-Thomas
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Contributions

S Gaillard (article author, study project manager, protocol writing, methodology, interpretation of results); A Bertholet-Thomas (main project coordinator, protocol writing, patient recruitment); P Cochat (protocol writing, patient recruitment); L Roche, C Mercier, F Subtil (statistical plan and analysis); S Lemoine, G Deschênes, D Morin, B Ranchin, J Bacchetta (patient recruitment); C Vianey-Saban, C Acquaviva-Bourdain (cysteine and cysteamine assessments); Eurielle Bodénan, Valérie Laudy (Study coordination, Clinical research associates), Cécile Rouges, Setareh Zarrabian (local study coordinators); P Nony, B Kassai (methodology, interpretation of results). All authors read and approved the final manuscript.

Corresponding author

Correspondence to Segolene Gaillard.

Ethics declarations

Ethics approval and consents to participate

This study was approved by the French Ethic committee (CPP Sud Est II) on 8 September 2010. The study was conducted in accordance with the French legislation, the Good Clinical Practice and the Declaration of Helsinki. Consents or assents were obtained from all participants and/or their parents/legal guardians before any procedures started.

Consent for publication

Not applicable.

Competing interests

Investigators (and their teams) of CrYSTobs study were also investigators of Raptor studies which covered the development of Procysbi®. The clinical investigation center of Lyon coordinated the Raptor studies in France.

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Gaillard, S., Roche, L., Lemoine, S. et al. Adherence to cysteamine in nephropathic cystinosis: A unique electronic monitoring experience for a better understanding. A prospective cohort study: CrYSTobs. Pediatr Nephrol 36, 581–589 (2021). https://doi.org/10.1007/s00467-020-04722-0

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