Long-term effectiveness of enzyme replacement therapy in children with Gaucher disease: results from the NCS-LSD cohort study
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To determine the effectiveness of enzyme replacement therapies (ERT) for children with Gaucher disease (GD).
A longitudinal cohort study including prospective and retrospective clinical data. Age- and gender-adjusted treatment effects were estimated using generalised linear mixed models. Children on treatment contributed data before and during treatment. Children not on treatment contributed natural history data.
Consenting children (N = 25, aged 1.1 to 15.6 years) with a diagnosis of GD (14 with GD1 and 11 with GD3) who attended a specialist treatment centre in England. At recruitment, 24 patients were receiving ERT (mean treatment duration, 5.57 years; range 0-13.7 years).
Clinical outcomes chosen to reflect disease progression, included platelet count; haemoglobin and absence/presence of bone pain.
Duration of ERT was associated with statistically significant improvements in platelet count (p < 0.001), haemoglobin (p < 0.001), and reported bone pain (p = 0.02). The magnitude of effect on haematological parameters was greater in children with GD3 than in those with GD1.
These data provide further evidence of the long-term effectiveness of ERT in children with GD.
KeywordsPlatelet Count Enzyme Replacement Therapy Bone Pain Fabry Disease Gauche Disease
We thank study site personnel Marie Meehan, Andrea Hill, Debbie Hugh, Sarah West, Sandhya Maddukuri, Kate Blackler, Hannah Russon, Navneeta Reddy, Jennifer Hutchinson, Nike Aina and Noura Hamdi for their hard work in the recruitment of patients to this study, and in managing the patients’ data at each of the seven sites. We thank the late Ed Wraith, Robin Lachmann, Atul Mehta, Ashok Vellodi, Patrick Deegan, Tim Cox, Chris Hendriksz, Philip Lee, Uma Ramaswami, Simon Jones and Tanya Collin-Histed for their contribution to the design and conduct of the study. Thanks to Rob Anderson for his contribution to the design of the study and data collection forms, to Sheena Oxer and Louise Klinger for their contribution to the set-up and coordination of the study, and to Laura Cocking for her help in the design and the management of the databases throughout the study.
We are grateful to all members of the LSD patient support groups and the Trial Steering Committee. Finally, special thanks to the patients and their families who allowed us to collect information from their hospital records and gave their time to complete the questionnaires. We thank them for their invaluable contribution.
Compliance with ethics guidelines
Conflicts of interest
Derralynn Hughes has received funding for research and travel to meetings, honoraria for lectures and consultancy projects or advisory boards from Shire HGT, Genzyme, Amicus, Actelion, and Biomarin. Consultancy and advisory board work is administered via UCL business and used in part to fund research.
Stephen Waldek is a member of the Fabry Registry Board and the Fabry Expert Group and has received funding for research, and honoraria for lectures and consultancy on research studies from Shire HGT and Genzyme. He has also received research grants from Biomarin, Synageva and Amicus.
Gregory M. Pastores has received funding for research and travel to meetings, honoraria for lectures and consultancy projects or advisory boards from Shire HGT, Genzyme, Amicus, Actelion, and Biomarin.
This study was funded by a National Institute for Health Research Health Technology Assessment programme project grant (No: 05/04/01).
- Anderson LJ, Henley W, Wyatt KM, et al (2014) Long-term effectiveness of enzyme replacement therapy in adults with Gaucher disease: results from the NCS-LSD cohort study. J Inherit Metab Dis. doi: 10.1007/s10545-014-9680-0
- Henley W, Anderson LJ, Wyatt KM, Nikolaou V, Anderson R, Logan S (2014) The NCS-LSD cohort study: a description of the methods and analyses used to assess the long-term effectiveness of enzyme replacement therapy and substrate reduction therapy in patients with Lysosomal Storage Disorders. J Inherit Metab Dis. doi: 10.1007/s10545-014-9679-6