Abstract
Objectives
To determine the effectiveness of enzyme replacement therapy (ERT) for adults with late-onset Pompe disease.
Design
A longitudinal cohort study including prospective and retrospective clinical outcome data. Age- and gender-adjusted treatment effects were estimated using generalised linear mixed models. Treated patients contributed data before and during treatment. Untreated patients contributed natural history data.
Participants
Consenting adults (N = 62) with a diagnosis of late-onset Pompe disease who attended a specialist treatment centre in England. This cohort represented 83 % of all patients in the UK with a confirmed diagnosis of this rare condition. At study entry, all but three patients were receiving ERT (range of treatment duration, 0 to 3.1 years).
Outcome measures
Percent predicted forced vital capacity (%FVC); ventilation dependency; mobility; 6 min walk test (6MWT); muscle strength and body mass index (BMI).
Results
An association was found between time on ERT and significant increases in the distance walked in the 6MWT (p < 0.001) and muscle strength scores (p < 0.001). Improvements in both these measures were seen over the first 2 years of treatment with ERT. No statistically significant relationship was found between time on ERT and respiratory function or in BMI.
Conclusions
These data provide some further evidence of the effectiveness of ERT in adults with late-onset Pompe disease.
Synopsis
The results of this longitudinal cohort study of 62 adults with late-onset Pompe disease, provide further evidence on the effectiveness of ERT in this rare condition.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Angelini C, Semplicini C, Ravaglia S et al (2012) Observational clinical study in juvenile-adult glycogenosis type 2 patients undergoing enzyme replacement therapy for up to 4 years. J Neurol 259(5):952–958
Bembi B, Pisa FE, Confalonieri M et al (2010) Long-term observational, non-randomized study of enzyme replacement therapy in late-onset glycogenosis type II. J Inherit Metab Dis 33(6):727–735
Bernstein DL, Bialer MG, Mehta L, Desnick RJ (2010) Pompe disease: dramatic improvement in gastrointestinal function following enzyme replacement therapy. A report of three later-onset patients. Mol Genet Metab 101(2–3):130–133
Engel AG, Gomez MR, Seybold ME, Lambert EH (1973) The spectrum and diagnosis of acid maltase deficiency. Neurology 23(1):95–106
Gungor D, de Vries JM, Hop WC et al (2011) Survival and associated factors in 268 adults with Pompe disease prior to treatment with enzyme replacement therapy. Orphanet J Rare Dis 6:34
Gungor D, Kruijshaar ME, Plug I et al (2013) Impact of enzyme replacement therapy on survival in adults with Pompe disease: results from a prospective international observational study. Orphanet J Rare Dis 8(1):49
Hagemans ML, Winkel LP, Van Doorn PA et al (2005) Clinical manifestation and natural course of late-onset Pompe’s disease in 54 Dutch patients. Brain 128(Pt 3):671–677
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. JIMD Rep
Hirschhorn R, Reuser AJJ (2001) Glycogen storage disease type II: acid alpha-glucosidase (Acid Maltase) deficiency. In: Scriver C, Beaudet A, Sly W, Valle D (eds) The metabolic and molecular bases of inherited disease, 8th edn. McGraw-Hill, New York, pp 3389–3420
Kishnani PS, Hwu WL, Mandel H, Nicolino M, Yong F, Corzo D (2006a) A retrospective, multinational, multicenter study on the natural history of infantile-onset Pompe disease. J Pediatr 148(5):671–676
Kishnani PS, Steiner RD, Bali D et al (2006b) Pompe disease diagnosis and management guideline. Genet Med 8(5):267–288
Kishnani PS, Corzo D, Nicolino M et al (2007) Recombinant human acid [alpha]-glucosidase: major clinical benefits in infantile-onset Pompe disease. Neurology 68(2):99–109
Kishnani PS, Corzo D, Leslie ND et al (2009) Early treatment with alglucosidase alpha prolongs long-term survival of infants with Pompe disease. Pediatr Res 66(3):329–335
Papadimas GK, Terzis G, Spengos K et al (2011) Bone mineral density in adult patients with Pompe disease. Bone 48(2):417, author reply 418–419
Regnery C, Kornblum C, Hanisch F et al (2012) 36 months observational clinical study of 38 adult Pompe disease patients under alglucosidase alfa enzyme replacement therapy. J Inherit Metab Dis 35(5):837–845
Schuller A, Wenninger S, Strigl-Pill N, Schoser B (2012) Toward deconstructing the phenotype of late-onset Pompe disease. Am J Med Genet C: Semin Med Genet 160(1):80–88
Slonim AE, Bulone L, Ritz S, Goldberg T, Chen A, Martiniuk F (2000) Identification of two subtypes of infantile acid maltase deficiency. J Pediatr 137(2):283–285
Strothotte S, Strigl-Pill N, Grunert B et al (2010) Enzyme replacement therapy with alglucosidase alfa in 44 patients with late-onset glycogen storage disease type 2: 12-month results of an observational clinical trial. J Neurol 257(1):91–97
Toscano A, Schoser B (2012) Enzyme replacement therapy in late-onset Pompe disease: a systematic literature review. J Neurol 260(4):951–959
van Capelle CI, Winkel LP, Hagemans ML et al (2008) Eight years experience with enzyme replacement therapy in two children and one adult with Pompe disease. Neuromuscul Disord 18(6):447–452
van den Berg LE, Zandbergen AA, van Capelle CI et al (2010) Low bone mass in Pompe disease: muscular strength as a predictor of bone mineral density. Bone 47(3):643–649
Van den Hout H, Reuser AJ, Vulto AG, Loonen MC, Cromme-Dijkhuis A, Van der Ploeg AT (2000) Recombinant human alpha-glucosidase from rabbit milk in Pompe patients. Lancet 356(9227):397–398
Van den Hout JM, Reuser AJ, de Klerk JB, Arts WF, Smeitink JA, Van der Ploeg AT (2001) Enzyme therapy for pompe disease with recombinant human alpha-glucosidase from rabbit milk. J Inherit Metab Dis 24(2):266–274
van den Hout HM, Hop W, van Diggelen OP et al (2003) The natural course of infantile Pompe’s disease: 20 original cases compared with 133 cases from the literature. Pediatrics 112(2):332–340
Van der Beek NA, Hagemans ML, Reuser AJ et al (2009) Rate of disease progression during long-term follow-up of patients with late-onset Pompe disease. Neuromuscul Disord 19(2):113–117
van der Beek NA, de Vries JM, Hagemans ML et al (2012) Clinical features and predictors for disease natural progression in adults with Pompe disease: a nationwide prospective observational study. Orphanet J Rare Dis 7:88
van der Ploeg AT, Clemens PR, Corzo D et al (2010) A randomized study of alglucosidase alfa in late-onset Pompe’s disease. N Engl J Med 362(15):1396–1406
van der Ploeg AT, Barohn R, Carlson L et al (2012) Open-label extension study following the Late-Onset Treatment Study (LOTS) of alglucosidase alfa. Mol Genet Metab 107(3):456–461
Wokke JH, Ausems MG, van den Boogaard MJ et al (1995) Genotype-phenotype correlation in adult-onset acid maltase deficiency. Ann Neurol 38(3):450–454
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
Acknowledgments
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, Derralynn Hughes, 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 Lysosomal Storage Disorders patient support groups for the advice and support and thank all members of the Trial Steering Committee for their advice along the way.
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
Informed consent
All procedures were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000 (5). Informed consent was obtained from all patients before being included in the study.
Funding
This study was funded by a National Institute for Health Research (NIHR) Health Technology Assessment programme project grant (No: 05/04/01) and was supported by the NIHR Collaboration for Leadership in Applied Health Research and Care South West Peninsula at the Royal Devon and Exeter NHS Foundation Trust. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health.
Competing interest
Lindsey Anderson, Katrina Wyatt, Stuart Logan, Vasilis Nikolaou and William Henley declare that they have no conflicts of interest.
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.
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.
Robin Lachmann has received honoraria and consultancy fees from Genzyme, Shire and Actelion, and unrestricted educational grant funding from Genzyme and Shire HGT.
Author information
Authors and Affiliations
Corresponding author
Additional information
Communicated by: Marc Patterson
Rights and permissions
About this article
Cite this article
Anderson, L.J., Henley, W., Wyatt, K.M. et al. Effectiveness of enzyme replacement therapy in adults with late-onset Pompe disease: results from the NCS-LSD cohort study. J Inherit Metab Dis 37, 945–952 (2014). https://doi.org/10.1007/s10545-014-9728-1
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10545-014-9728-1