Abstract
Objectives
To determine the effectiveness of enzyme replacement therapies (ERT) for children with Gaucher disease (GD).
Design
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.
Participants
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).
Outcome measures
Clinical outcomes chosen to reflect disease progression, included platelet count; haemoglobin and absence/presence of bone pain.
Results
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.
Conclusions
These data provide further evidence of the long-term effectiveness of ERT in children with GD.
Similar content being viewed by others
References
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
Andersson H, Kaplan P, Kacena K, Yee J (2008) Eight-year clinical outcomes of long-term enzyme replacement therapy for 884 children with Gaucher disease type 1. Pediatrics 122(6):1182–1190
Biegstraaten M, Mengel E, Marodi L et al (2010) Peripheral neuropathy in adult type 1 Gaucher disease: a 2-year prospective observational study. Brain 133(10):2909–2919
Brady RO, Kanfer J, Shapiro D (1965) The Metabolism of Glucocerebrosides. I. Purification and Properties of a Glucocerebroside-Cleaving Enzyme from Spleen Tissue. J Biol Chem 240:39–43
Charrow J, Andersson HC, Kaplan P et al (2000) The Gaucher registry: demographics and disease characteristics of 1698 patients with Gaucher disease. Arch Intern Med 160(18):2835–2843
Charrow J, Andersson HC, Kaplan P et al (2004) Enzyme replacement therapy and monitoring for children with type 1 Gaucher disease: consensus recommendations. J Pediatr 144(1):112–120
Charrow J, Dulisse B, Grabowski GA, Weinreb NJ (2007) The effect of enzyme replacement therapy on bone crisis and bone pain in patients with type 1 Gaucher disease. Clin Genet 71(3):205–211
Cox T, Lachmann R, Hollak C et al (2000) Novel oral treatment of Gaucher’s disease with N-butyldeoxynojirimycin (OGT 918) to decrease substrate biosynthesis. Lancet 355(9214):1481–1485
Deegan PB, Pavlova E, Tindall J et al (2011) Osseous manifestations of adult Gaucher disease in the era of enzyme replacement therapy. Medicine (Baltimore) 90(1):52–60
Elstein D, Cohn GM, Wang N, Djordjevic M, Brutaru C, Zimran A (2011a) Early achievement and maintenance of the therapeutic goals using velaglucerase alfa in type 1 Gaucher disease. Blood Cells Mol Dis 46(1):119–123
Elstein D, Foldes AJ, Zahrieh D et al (2011b) Significant and continuous improvement in bone mineral density among type 1 Gaucher disease patients treated with velaglucerase alfa: 69-month experience, including dose reduction. Blood Cells Mol Dis 47(1):56–61
Gonzalez DE, Turkia HB, Lukina EA et al (2013) Enzyme replacement therapy with velaglucerase alfa in Gaucher disease: Results from a randomized, double-blind, multinational, Phase 3 study. Am J Hematol 88(3):166–171
Grabowski GA, Barton NW, Pastores G et al (1995) Enzyme therapy in type 1 Gaucher disease: comparative efficacy of mannose-terminated glucocerebrosidase from natural and recombinant sources. Ann Intern Med 122(1):33–39
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
Kaplan P, Andersson HC, Kacena KA, Yee JD (2006) The clinical and demographic characteristics of nonneuronopathic Gaucher disease in 887 children at diagnosis. Arch Pediatr Adolesc Med 160(6):603–608
Pastores GM, Patel MJ, Firooznia H (2000) Bone and joint complications related to Gaucher disease. Curr Rheumatol Rep 2(2):175–180
Pastores GM, Weinreb NJ, Aerts H et al (2004) Therapeutic goals in the treatment of Gaucher disease. Semin Hematol 41(4 Suppl 5):4–14
Rodrigue SW, Rosenthal DI, Barton NW, Zurakowski D, Mankin HJ (1999) Risk factors for osteonecrosis in patients with type 1 Gaucher’s disease. Clin Orthop Relat Res 362:201–207
Rosenthal DI, Scott JA, Barranger J et al (1986) Evaluation of Gaucher disease using magnetic resonance imaging. J Bone Joint Surg Am 68(6):802–808
Schiffmann R, Mankin H, Dambrosia JM et al (2002) Decreased bone density in splenectomized Gaucher patients receiving enzyme replacement therapy. Blood Cells Mol Dis 28(2):288–296
Sims KB, Pastores GM, Weinreb NJ et al (2008) Improvement of bone disease by imiglucerase (Cerezyme) therapy in patients with skeletal manifestations of type 1 Gaucher disease: results of a 48-month longitudinal cohort study. Clin Genet 73(5):430–440
Tayebi N, Callahan M, Madike V et al (2001) Gaucher disease and parkinsonism: a phenotypic and genotypic characterization. Mol Genet Metab 73(4):313–321
Weinreb NJ, Charrow J, Andersson HC et al (2002) Effectiveness of enzyme replacement therapy in 1028 patients with type 1 Gaucher disease after 2 to 5 years of treatment: a report from the Gaucher Registry. Am J Med 113(2):112–119
Weinreb N, Barranger J, Packman S et al (2007) Imiglucerase (Cerezyme) improves quality of life in patients with skeletal manifestations of Gaucher disease. Clin Genet 71(6):576–588
Wenstrup RJ, Kacena KA, Kaplan P et al (2007) Effect of enzyme replacement therapy with imiglucerase on BMD in type 1 Gaucher disease. J Bone Miner Res 22(1):119–126
Wyatt K, Henley W, Anderson L et al (2012) The effectiveness and cost-effectiveness of enzyme and substrate replacement therapies: a longitudinal cohort study of people with lysosomal storage disorders. Health Technol Assess 16(39):1–543
Zimran A, Altarescu G, Philips M et al (2010) Phase 1/2 and extension study of velaglucerase alfa replacement therapy in adults with type 1 Gaucher disease: 48-month experience. Blood 115(23):4651–4656
Acknowledgements
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
ᅟ
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.
Funding
This study was funded by a National Institute for Health Research Health Technology Assessment programme project grant (No: 05/04/01).
Author information
Authors and Affiliations
Corresponding author
Additional information
Communicated by: Frits Wijburg
Rights and permissions
About this article
Cite this article
Anderson, L.J., Henley, W., Wyatt, K.M. et al. Long-term effectiveness of enzyme replacement therapy in children with Gaucher disease: results from the NCS-LSD cohort study. J Inherit Metab Dis 37, 961–968 (2014). https://doi.org/10.1007/s10545-014-9693-8
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10545-014-9693-8