TY - JOUR
T1 - The role of enzyme replacement therapy in severe Hunter syndrome-an expert panel consensus
AU - Muenzer, Joseph
AU - Bodamer, Olaf
AU - Burton, Barbara
AU - Clarke, Lorne
AU - Frenking, Gudrun Schulze
AU - Giugliani, Roberto
AU - Jones, Simon
AU - Rojas, Maria Verónica Muñoz
AU - Scarpa, Maurizio
AU - Beck, Michael
AU - Harmatz, Paul
N1 - Funding Information:
Financial Disclosure Drs. Muenzer, Bodamer, Burton, Clarke, Giugliani, Jones, Muñoz Rojas, Schulze Frenking, Scarpa, Beck, and Harmatz have received honoraria, travel grants, or research grants from Shire Human Genetic Therapies, Inc.
PY - 2012/1
Y1 - 2012/1
N2 - Intravenous enzyme replacement therapy (ERT) with idursulfase for Hunter syndrome has not been demonstrated to and is not predicted to cross the blood-brain barrier. Nearly all published experience with ERT with idursulfase has therefore been in patients without cognitive impairment (attenuated phenotype). Little formal guidance is available on the issues surrounding ERT in cognitively impaired patients with the severe phenotype. An expert panel was therefore convened to provide guidance on these issues. The clinical experience of the panel with 66 patients suggests that somatic improvements (e.g., reduction in liver volume, increased mobility, and reduction in frequency of respiratory infections) may occur in most severe patients. Cognitive benefits have not been seen. It was agreed that, in general, severe patients are candidates for at least a 6-12-month trial of ERT, excluding patients who are severely neurologically impaired, those in a vegetative state, or those who have a condition that may lead to near-term death. It is imperative that the treating physician discuss the goals of treatment, methods of assessment of response, and criteria for discontinuation of treatment with the family before ERT is initiated. Conclusion: The decision to initiate ERT in severe Hunter syndrome should be made by the physician and parents and must be based on realistic expectations of benefits and risks, with the understanding that ERT may be withdrawn in the absence of demonstrable benefits.
AB - Intravenous enzyme replacement therapy (ERT) with idursulfase for Hunter syndrome has not been demonstrated to and is not predicted to cross the blood-brain barrier. Nearly all published experience with ERT with idursulfase has therefore been in patients without cognitive impairment (attenuated phenotype). Little formal guidance is available on the issues surrounding ERT in cognitively impaired patients with the severe phenotype. An expert panel was therefore convened to provide guidance on these issues. The clinical experience of the panel with 66 patients suggests that somatic improvements (e.g., reduction in liver volume, increased mobility, and reduction in frequency of respiratory infections) may occur in most severe patients. Cognitive benefits have not been seen. It was agreed that, in general, severe patients are candidates for at least a 6-12-month trial of ERT, excluding patients who are severely neurologically impaired, those in a vegetative state, or those who have a condition that may lead to near-term death. It is imperative that the treating physician discuss the goals of treatment, methods of assessment of response, and criteria for discontinuation of treatment with the family before ERT is initiated. Conclusion: The decision to initiate ERT in severe Hunter syndrome should be made by the physician and parents and must be based on realistic expectations of benefits and risks, with the understanding that ERT may be withdrawn in the absence of demonstrable benefits.
KW - Cognitive impairment
KW - Enzyme replacement therapy
KW - Hunter syndrome
KW - Idursulfase
KW - Mucopolysaccharidosis II
KW - Severe phenotype
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U2 - 10.1007/s00431-011-1606-3
DO - 10.1007/s00431-011-1606-3
M3 - Article
C2 - 22037758
AN - SCOPUS:84857061064
VL - 171
SP - 181
EP - 188
JO - European Journal of Pediatrics
JF - European Journal of Pediatrics
SN - 0340-6199
IS - 1
ER -