Postauthorization safety study of betaine anhydrous
Por:
Mütze U, Gleich F, Garbade SF, Plisson C, Aldámiz-Echevarría L, Arrieta F, Ballhausen D, Zielonka M, Ramadža DP, Baumgartner MR, Cano A, Jiménez MCG, Dionisi-Vici C, Ješina P, Blom HJ, Couce ML, Meavilla-Olivas SM, Mention K, Mochel F, Morris AAM, Mundy H, Redonnet-Vernhet I, Santra S, Schiff M, Servais A, Vitoria I, Huemer M, Kožich V and Kölker S
Publicada:
1 jul 2022
Ahead of Print:
1 abr 2022
Resumen:
Patient registries for rare diseases enable systematic data collection and can also be used to facilitate postauthorization safety studies (PASS) for orphan drugs. This study evaluates the PASS for betaine anhydrous (Cystadane), conducted as public private partnership (PPP) between the European network and registry for homocystinurias and methylation defects and the marketing authorization holder (MAH). Data were prospectively collected, 2013-2016, in a noninterventional, international, multicenter, registry study. Putative adverse and severe adverse events were reported to the MAH's pharmacovigilance. In total, 130 individuals with vitamin B-6 nonresponsive (N = 54) and partially responsive (N = 7) cystathionine beta-synthase (CBS) deficiency, as well as 5,10-methylenetetrahydrofolate reductase (MTHFR; N = 21) deficiency and cobalamin C (N = 48) disease were included. Median (range) duration of treatment with betaine anhydrous was 6.8 (0-9.8) years. The prescribed betaine dose exceeded the recommended maximum (6 g/day) in 49% of individuals older than 10 years because of continued dose adaptation to weight; however, with disease-specific differences (minimum: 31% in B-6 nonresponsive CBS deficiency, maximum: 67% in MTHFR deficiency). Despite dose escalation no new or potential risk was identified. Combined disease-specific treatment decreased mean +/- SD total plasma homocysteine concentrations from 203 +/- 116 to 81 +/- 51 mu mol/L (p < 0.0001), except in MTHFR deficiency. Recommendations for betaine anhydrous dosage were revised for individuals >= 10 years. PPPs between MAH and international scientific consortia can be considered a reliable model for implementing a PASS, reutilizing well-established structures and avoiding data duplication and fragmentation.
Filiaciones:
Mütze U:
Division of Child Neurology and Metabolic Medicine, Centre for Child and Adolescent Medicine, University Hospital, Heidelberg, Germany
Gleich F:
Division of Child Neurology and Metabolic Medicine, Centre for Child and Adolescent Medicine, University Hospital, Heidelberg, Germany
Garbade SF:
Division of Child Neurology and Metabolic Medicine, Centre for Child and Adolescent Medicine, University Hospital, Heidelberg, Germany
Plisson C:
Recordati Rare Diseases, Puteaux, France
Aldámiz-Echevarría L:
Instituto de Investigación Santiago de Compostela (IDIS), Spain
Arrieta F:
Endocrinology & Nutrition, Metabolic Congenital Disease, H.U. Ramon y Cajal, Madrid, Spain
Ballhausen D:
Pediatric Unit for Metabolic Diseases, Woman-Mother-Child Department, Lausanne University Hospital, Lausanne, Switzerland
Zielonka M:
Division of Child Neurology and Metabolic Medicine, Centre for Child and Adolescent Medicine, University Hospital, Heidelberg, Germany
Ramadža DP:
Department of Pediatrics, University Hospital Centre Zagreb and University of Zagreb, School of Medicine, Zagreb, Croatia
Baumgartner MR:
Division of Metabolism and Children's Research Center, University Children's Hospital, University of Zurich, Zurich, Switzerland
Cano A:
Centre de Référence des Maladies Héréditaires du Métabolisme, CHU La Timone Enfants, Marseille, France
Jiménez MCG:
Metabolic Department, University Children Miguel Servet Hospital, IIS, Aragon, Spain
Dionisi-Vici C:
Division of Metabolism, Bambino Gesù Children's Hospital IRCCS, Rome, Italy
Ješina P:
Department of Pediatrics and Inherited Metabolic Disorders, Charles University-First Faculty of Medicine and General University Hospital, Prague, Czech Republic
Blom HJ:
Department of Clinical Genetics, Center for Lysosomal and Metabolic Diseases, Erasmus Medical Center, Rotterdam, Netherlands
Couce ML:
Unit of Diagnosis and Treatment of Congenital Metabolic Diseases, Service of Neonatology, Department of Pediatrics, Hospital Clínico Universitario de Santiago, CIBERER, Health Research Institute of Santiago de Compostela (IDIS), Santiago de Compostela, Spain
Meavilla-Olivas SM:
Pediatrics, Gastroenterology, Hepatology and Nutrition, Hospital Sant Joan de Déu, Barcelona, Spain
Mention K:
Centre de Référence des Maladies Héréditaires du Métabolisme, Hôpital Jeanne de Flandre, Lille, France
Mochel F:
AP.HP, Sorbonne University, Reference Center for Adult Neurometabolic Diseases, La Pitié-Salpêtrière University Hospital, Paris, France
Morris AAM:
Alder Hey Children's NHS Foundation Trust, Liverpool, UK
Manchester Centre for Genomic Medicine, Manchester University Hospitals NHS Trust, Manchester, UK
Mundy H:
Evelina London Children's Hospital, London, UK
Redonnet-Vernhet I:
Endocrinology, Nutrition and Metabolic Diseases, Haut-Lévêque Hospital, Bordeaux University, Bordeaux, France
Santra S:
Department of Clinical Inherited Metabolic Disorders, Birmingham Women's and Children's NHS Foundation Trust, Birmingham, UK
Schiff M:
Necker Hospital, APHP, Reference Center for Inborn Error of Metabolism and Filière G2M, Pediatrics Department, University of Paris, Paris, France
Inserm UMR_S1163, Institut Imagine, Paris, France
Servais A:
Nephrology and Transplantation, MAMEA Reference Center, Necker hospital, APHP, Paris, France
Vitoria I:
Unit of Metabolic Disorders, Universitary Hospital La Fe, Valencia, Spain
Huemer M:
Division of Metabolism and Children's Research Center, University Children's Hospital, University of Zurich, Zurich, Switzerland
Department of Pediatrics, Landeskrankenhaus Bregenz, Bregenz, Austria
Kožich V:
Department of Pediatrics and Inherited Metabolic Disorders, Charles University-First Faculty of Medicine and General University Hospital, Prague, Czech Republic
Kölker S:
Division of Child Neurology and Metabolic Medicine, Centre for Child and Adolescent Medicine, University Hospital, Heidelberg, Germany
Green Submitted, Green Published, hybrid
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