Study details

RaDiCo-MPS - Mucopolysaccharidosis patients in France in the era of specific therapeutics

RaDiCo-MPS

Ongoing study

The primary objective of the MPS cohort is to characterize the epidemiology and natural history of mucopolysaccharidoses (MPS) by compiling a retrospective and prospective collection of detailed phenotypic data from French patients affected by these conditions.
Secondary objectives include conducting an in-depth assessment of the overall benefit of current treatments—including their impact on quality of life—and establishing genotype-phenotype correlations for each type of MPS.
Finally, the exploratory objective is to contribute to the identification of new, relevant biomarkers for future clinical trials, by establishing a list of biomarkers useful for therapeutic management and the improvement of patient monitoring.

The RaDiCo-MPS cohort is a national, multicenter, non-interventional, observational, longitudinal, descriptive, retrospective, and prospective study sponsored by Inserm and coordinated by the RaDiCo platform. It involves pediatric and adult patients with mucopolysaccharidosis (MPS) who are followed in the French network of Reference and Competence Centers for Lysosomal and Inherited Metabolic Diseases (G2M network), consisting of 8 Reference Centers and 3 Competence Centers. The enrollment period is set at 9 years, extended through June 2027, and each enrolled patient will be followed for 5 years, bringing the total duration of the study to 16 years and 6 months, with follow-up scheduled through June 2032.
MPS are rare lysosomal storage disorders caused by the accumulation of glycosaminoglycans in lysosomes, leading to progressive multiorgan involvement. Seven clinical subtypes have been identified (MPS I through IV, VI, VII, and IX), in addition to multiple sulfatase deficiency. Their overall incidence is estimated to be between 1 in 25,000 and 1 in 30,000 births. These are chronic, progressive diseases involving skeletal, visceral, ENT, cardiac, respiratory, and sometimes neurocognitive involvement, with severity varying greatly depending on the subtype. The advent of specific treatments (enzyme replacement therapy, hematopoietic stem cell transplantation) has altered the prognosis, although their overall benefit on quality of life and their cost-effectiveness have not yet been fully evaluated.
The study population includes prevalent patients—those diagnosed since 1973 and still under follow-up in France—and incident patients diagnosed during the study. Approximately 950 patients were diagnosed between 1973 and 2013, half of whom are believed to still be alive; a total of approximately 500 patients are expected to be included in the cohort. The diagnosis is based on a significant enzyme deficiency associated with abnormal urinary excretion of glycosaminoglycans, supplemented by mutation analysis. There are no exclusion criteria. Data from deceased patients may be collected, unless the patient or their legal representatives expressly objected during the patient’s lifetime.
Patients are identified and recruited through the G2M network, as well as with the assistance of French laboratories specializing in the diagnosis of metabolic diseases and patient organizations. The study does not alter the usual course of care and does not require any additional tests; however, it does involve the collection of additional biological samples (plasma and urine) at enrollment and then annually while on treatment.
The cohort combines retrospective data—drawn from medical records and existing databases—with prospective data collected via the RaDiCo-MPS eCRF during routine follow-up visits, which occur one to four times a year depending on the patient’s age and disease progression. The data collected include clinical characteristics (growth, signs, complications by system, psychomotor and cognitive development), radiological, electrophysiological, biochemical (urinary GAGs, enzyme activities, specific antibodies), and molecular data, as well as questionnaires on quality of life and global impression of change (CGI-I, PGI-I), and medical-social questionnaires.
The analyses will be primarily descriptive, illustrated by appropriate graphical representations, including calculations of means and standard deviations or percentages and confidence intervals, by visit and over the entire duration of the study, according to MPS subgroups. Comparative tests (ANOVA, chi-square, Fisher’s exact test) and Kaplan-Meier survival curves with the log-rank test will be used. Explanatory multivariate analyses (PCA, CDA, logistic regression) will be used to examine associations between treatments and patient outcomes, between phenotype and genotype, and between candidate biomarkers and therapeutic response. The health economic evaluation of healthcare costs will be the subject of a subsequent protocol amendment.
The RaDiCo-MPS cohort thus constitutes a structured database of clinical, biological, genetic, and quality-of-life data collected over the long term from a nationally coordinated network of expert centers, enabling a better characterization of the natural history and management of mucopolysaccharidoses in France.

Rare Diseases MPS Genetics Lysosomal disease Quality of Life Cohort

Anaesthesiology Andrology and urology Cardiology and vascular medicine Dentistry Dermatology Gastroenterology Hematology Hepatology Medical genetics Neurology Ophthalmology Orthopaedics and traumatology Otolaryngology Paediatrics Physical and Rehabilitation Medicine Psychiatry Public, environmental and occupational health Pulmonary medicine Radiology and nuclear medicine Rheumatology Transplantation

Mucopolysaccharidosis

Socio-demographic and economic determinants Socio-demographic and economic determinants: Employment Socio-demographic and economic determinants: Education level Socio-demographic and economic determinants: Family situation Socio-demographic and economic determinants: Age Biological determinants Biological determinants: Genetic predisposition Biological determinants: Sex

Yes

France

Oui

Comité de Pilotage : Bénédicte HERON, Samia PICHARD, Anais BRASSIER, François FEILLET, Elise SACAZE
Comité Scientifique : Bénédicte HERON, Anais BRASSIER, Catherine CAILLAUD, Samia PICHARD, Elise SACAZE, Anne-Sophie GUEMANN, François FEILLET, Elise JEANNESSON, Magali GORCE, Delphine GENEVAZ, Equipe Projet RaDiCo + Sonia GUEGUEN

Oui

Filière G2M

Individus

Etude observationnelle

Cohorte

Autre

Non

Le critère d’évaluation principal est l’évolution à long terme des caractéristiques cliniques, biologiques et paracliniques des patients atteints de mucopolysaccharidose (MPS), notamment de type IVA traités par élosulfase alfa. Cette évolution sera évaluée à partir de données cliniques (croissance, signes, symptômes, complications, développement psychomoteur, fonctions cognitives et handicap), radiologiques, électrophysiologiques, biochimiques et moléculaires. Les données seront recueillies lors de l’inclusion, puis annuellement au cours du suivi, et complétées rétrospectivement pour certaines données à partir des dossiers médicaux pour les patients déjà diagnostiqués.

Les critères d’évaluation secondaires visent à évaluer l’évolution à long terme des patients atteints de mucopolysaccharidose (MPS) de type IVA ayant interrompu le traitement par élosulfase alfa ou n’ayant jamais reçu ce traitement. Elles comprennent la description de la prise en charge et de l’évolution de la maladie avant et en l’absence de traitement spécifique, ainsi que sous traitement, à partir de données médicales et fonctionnelles, d’échelles et de questionnaires adaptés, de mesures de la qualité de vie, de l’impression globale d’amélioration rapportée par les cliniciens (CGI-I) et les patients (PGI-I), ainsi que de l’espérance de vie. L’étude vise également à identifier les mutations génétiques et à établir les relations génotype-phénotype pour chaque type de MPS.