PMID- 30871635
OWN - NLM
STAT- MEDLINE
DCOM- 20191003
LR  - 20200309
IS  - 1750-1172 (Electronic)
IS  - 1750-1172 (Linking)
VI  - 14
IP  - 1
DP  - 2019 Mar 14
TI  - Betaine anhydrous in homocystinuria: results from the RoCH registry.
PG  - 66
LID - 10.1186/s13023-019-1036-2 [doi]
LID - 66
AB  - BACKGROUND: The Registry of Adult and Paediatric Patients Treated with Cystadane(R) 
      - Homocystinuria (RoCH) is a non-interventional, observational, multi-centre, 
      post-authorization safety study that aimed to identify safety of betaine 
      anhydrous (Cystadane(R)) in the treatment of patients with inborn errors of 
      homocysteine metabolism (homocystinuria) in order to minimise the treatment 
      associated risks and establish better knowledge on its clinical use. The registry 
      included patients of all ages with homocystinuria who were treated with betaine 
      anhydrous in conjunction with other therapies. Clinical data were collected 
      retrospectively from 2007 to 2013, then prospectively up to February 2014. All 
      adverse events (AEs) reported during the study were recorded. The clinical and 
      biological status of patients was monitored at least once a year. RESULTS: A 
      total of 125 patients with homocystinuria (adults [> 18 years]: 50; paediatric 
      [</=18 years]: 75) were enrolled at 29 centres in France and Spain. Patients were 
      treated with betaine anhydrous for a mean duration of 7.4 +/- 4.3 years. The median 
      total daily dose of betaine anhydrous at the first and last study visits was 
      6 g/day for cystathionine beta-synthase (CBS)-deficient vitamin B6 responders and 
      9 g/day for methylenetetrahydrofolate reductase-deficient patients, while the 
      median daily dose increased in CBS-deficient B6 non-responders (from 6 to 
      9 g/day) and cobalamin metabolism-defective patients (from 3 to 6 g/day) between 
      the first and last visits. Treatment caused a mean overall reduction of 29% in 
      plasma homocysteine levels in the study population. A total of 277 AEs were 
      reported during the study, of which two non-serious AEs (bad taste and headache) 
      and one serious AE (interstitial lung disease) were considered to be drug 
      related. Overall, betaine anhydrous was well tolerated with no major safety 
      concerns. CONCLUSIONS: Data from the RoCH registry provided real-world evidence 
      on the clinical safety and efficacy of betaine anhydrous in the management of 
      homocystinuria in paediatric and adult patients.
FAU - Valayannopoulos, Vassili
AU  - Valayannopoulos V
AUID- ORCID: 0000-0003-3942-8234
AD  - Hopital Necker-Enfants Malades, Paris, France. vassilival.boston@gmail.com.
AD  - Sanofi Genzyme, 500 Kendall St, Cambridge, MA, 02140, USA. 
      vassilival.boston@gmail.com.
FAU - Schiff, Manuel
AU  - Schiff M
AD  - Hopital Robert Debre, Paris, France.
FAU - Guffon, Nathalie
AU  - Guffon N
AD  - Hopital Femme Mere Enfant, Bron, France.
FAU - Nadjar, Yann
AU  - Nadjar Y
AD  - Hopital Pitie-Salpetriere, Paris, France.
FAU - Garcia-Cazorla, Angels
AU  - Garcia-Cazorla A
AD  - Hospital St Joan de Deu, Barcelona, Spain.
FAU - Martinez-Pardo Casanova, Mercedes
AU  - Martinez-Pardo Casanova M
AD  - Hospital Universitario Ramon y Cajal, Madrid, Spain.
FAU - Cano, Aline
AU  - Cano A
AD  - Center of Reference for Inborn Metabolic Disease, CHU La Timone, Marseille, 
      France.
FAU - Couce, Maria L
AU  - Couce ML
AD  - Hospital Clinico Universitario, Santiago de Compostela-La Coruna, Spain.
FAU - Dalmau, Jaime
AU  - Dalmau J
AD  - Hospital Universitario y Politecnico La Fe, Valencia, Spain.
FAU - Pena-Quintana, Luis
AU  - Pena-Quintana L
AD  - Hospital Universitario Materno-Infantil, Universidad de Las Palmas de Gran 
      Canaria, CIBER OBN, Las Palmas, Spain.
FAU - Rigalleau, Vincent
AU  - Rigalleau V
AD  - Hopital Haut Leveque, Pessac, France.
FAU - Touati, Guy
AU  - Touati G
AD  - Hopital des Enfants, Toulouse, France.
FAU - Aldamiz-Echevarria, Luis
AU  - Aldamiz-Echevarria L
AD  - Hospital Universitario Cruces-Osakidetza, Barakaldo-Vizcaya, Spain.
FAU - Cathebras, Pascal
AU  - Cathebras P
AD  - CHU Hopital Nord, Saint-Etienne, France.
FAU - Eyer, Didier
AU  - Eyer D
AD  - CHU Hautepierre, Strasbourg, France.
FAU - Brunet, Dominique
AU  - Brunet D
AD  - CHU La Timone, Marseille, France.
FAU - Damaj, Lena
AU  - Damaj L
AD  - CHU Hopital Sud, Rennes, France.
FAU - Dobbelaere, Dries
AU  - Dobbelaere D
AD  - Medical Reference Center for Inherited Metabolic Diseases, Jeanne de Flandre 
      University Hospital and RADEME Research Team for Rare Metabolic and Developmental 
      Diseases, Lille, France.
FAU - Gay, Claire
AU  - Gay C
AD  - CHU Hopital Nord, Saint-Etienne, France.
FAU - Hieronimus, Sylvie
AU  - Hieronimus S
AD  - Hopital l'Archet, CHU de Nice, France.
FAU - Levrat, Virginie
AU  - Levrat V
AD  - Centre Hospitalier Annecy Genevois, Pringy, France.
FAU - Maillot, Francois
AU  - Maillot F
AD  - CHRU de Tours, Service de Medecine Interne, Universite Francois Rabelais, Tours, 
      France.
LA  - eng
PT  - Journal Article
PT  - Multicenter Study
PT  - Observational Study
PT  - Research Support, Non-U.S. Gov't
DEP - 20190314
PL  - England
TA  - Orphanet J Rare Dis
JT  - Orphanet journal of rare diseases
JID - 101266602
RN  - 0LVT1QZ0BA (Homocysteine)
RN  - 3SCV180C9W (Betaine)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Betaine/*administration & dosage/adverse effects
MH  - Child
MH  - Child, Preschool
MH  - Female
MH  - France
MH  - Homocysteine/blood
MH  - Homocystinuria/*drug therapy
MH  - Humans
MH  - Infant
MH  - Male
MH  - *Registries
MH  - Retrospective Studies
MH  - Spain
MH  - Treatment Outcome
MH  - Young Adult
PMC - PMC6419445
OTO - NOTNLM
OT  - Betaine anhydrous
OT  - Efficacy
OT  - Homocystinuria
OT  - RoCH registry
OT  - Safety
COIS- ETHICS APPROVAL AND CONSENT TO PARTICIPATE: Ethics approval is not mandatory for 
      non-interventional studies conducted in France and Spain. Data privacy collection 
      approval was obtained. An information sheet was provided to patients and verbal 
      consent was obtained in compliance with French and Spanish law for such a study. 
      CONSENT FOR PUBLICATION: Not applicable. COMPETING INTERESTS: All authors except 
      GT, BF and MS received payment from Orphan Europe directly or indirectly through 
      their institution/association for participation in the registry. VV is currently 
      an employee of Sanofi Genzyme. He performed most of this work while he was at 
      Necker-Enfants Malades University Hospital. LD has a conflict of interest with 
      Orphan Europe. FM has received an honorarium from Orphan Europe. The other 
      authors have no conflicts of interest to declare. PUBLISHER'S NOTE: Springer 
      Nature remains neutral with regard to jurisdictional claims in published maps and 
      institutional affiliations.
EDAT- 2019/03/16 06:00
MHDA- 2019/10/08 06:00
PMCR- 2019/03/14
CRDT- 2019/03/16 06:00
PHST- 2018/11/07 00:00 [received]
PHST- 2019/02/20 00:00 [accepted]
PHST- 2019/03/16 06:00 [entrez]
PHST- 2019/03/16 06:00 [pubmed]
PHST- 2019/10/08 06:00 [medline]
PHST- 2019/03/14 00:00 [pmc-release]
AID - 10.1186/s13023-019-1036-2 [pii]
AID - 1036 [pii]
AID - 10.1186/s13023-019-1036-2 [doi]
PST - epublish
SO  - Orphanet J Rare Dis. 2019 Mar 14;14(1):66. doi: 10.1186/s13023-019-1036-2.