Abstract
Background: In Australia, enzyme replacement therapy (ERT) for Fabry Disease (FD), both Agalsidase alfa (Replagal, Shire HGT) and beta (Fabrazyme, Genzyme), is funded and monitored through a specific government program. Agalsidase beta supply has been rationed by Genzyme since 2009 due to manufacturing issues. Consequently, the Australian Fabry Disease Advisory Committee has treated patients on Agalsidase beta at 50% of their usual dose from mid-2009, with a further reduction to 30% for some patients from late 2009.
Aim: To determine the clinical effect of Agalsidase beta dose reduction in the Australian FD patient cohort.
Methods: A questionnaire assessing FD symptoms was administered to 40 patients on long-term ERT. Clinical data from The Fabry Registry for patients receiving Agalsidase alfa or beta, for at least 2 years prior to the time of enforced Agalsidase beta dose reduction, were reviewed. Disease burden and quality of life (QOL) were graded using the Disease Severity Scoring System, Mainz Severity Score Index, Brief Pain Inventory and Short Form 36 Health Survey at 2 years before dose reduction, at the time of dose reduction and at the most recent clinical review following dose reduction.
Results: Disease severity and QOL scores did not change between the ERT groups. Males on Agalsidase beta reported lower energy levels after dose reduction, while no change was reported by females on either product or by males on a stable dose of Agalsidase alfa.
Conclusion: This study suggests that energy levels in male patients worsen after dose reduction of Agalsidase beta.
Keywords
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
Competing interests: None declared.
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsReferences
Aerts JM, Groener JE, Kuiper S, Donker-Koopman WE, Strijland A, Ottenhoff R, van Roomen C, Mirzaian M, Wijburg FA, Linthorst GE, Vedder AC, Rombach SM, Cox-Brinkman J, Somerharju P, Boot RG, Hollak CE, Brady RO, Poorthuis BJ (2008) Elevated globotriaosylsphingosine is a hallmark of Fabry disease. Proc Natl Acad Sci U S A 105(8):2812–2817
Aerts JM, Kallemeijn WW, Wegdam W, Joao Ferraz M, van Breemen MJ, Dekker N, Kramer G, Poorthuis BJ, Groener JE, Cox-Brinkman J, Rombach SM, Hollak CE, Linthorst GE, Witte MD, Gold H, van der Marel GA, Overkleeft HS, Boot RG (2011) Biomarkers in the diagnosis of lysosomal storage disorders: proteins, lipids, and inhibodies. J Inherit Metab Dis 34:605–619
Banikazemi M, Bultas J, Waldek S, Wilcox WR, Whitley CB, McDonald M, Finkel R, Packman S, Bichet DG, Warnock DG, Desnick RJ (2007) Agalsidase-beta therapy for advanced Fabry disease: a randomized trial. Ann Intern Med 146(2):77–86
Beck M (2002) Agalsidase alfa–a preparation for enzyme replacement therapy in Anderson-Fabry disease. Expert Opin Investig Drugs 11(6):851–858
Benichou B, Goyal S, Sung C, Norfleet AM, O'Brien F (2009) A retrospective analysis of the potential impact of IgG antibodies to agalsidase beta on efficacy during enzyme replacement therapy for Fabry disease. Mol Genet Metab 96(1):4–12
Cleeland CS (2002) Pain assessment: the advantages of using pain scales in lysosomal storage diseases. Acta Paediatr Suppl 91(439):43–47
Cole AL, Lee PJ, Hughes DA, Deegan PB, Waldek S, Lachmann RH (2007) Depression in adults with Fabry disease: a common and under-diagnosed problem. J Inherit Metab Dis 30(6):943–951
El Dib RP, Pastores GM (2010) Enzyme replacement therapy for Anderson-Fabry disease. Cochrane Database Syst Rev 5:CD006663
Eng CM, Guffon N, Wilcox WR, Germain DP, Lee P, Waldek S, Caplan L, Linthorst GE, Desnick RJ (2001) Safety and efficacy of recombinant human alpha-galactosidase A–replacement therapy in Fabry's disease. N Engl J Med 345(1):9–16
Garin O, Ferrer M, Pont A, Rue M, Kotzeva A, Wiklund I, Van Ganse E, Alonso J (2009) Disease-specific health-related quality of life questionnaires for heart failure: a systematic review with meta-analyses. Qual Life Res 18(1):71–85
Giannini EH, Mehta AB, Hilz MJ, Beck M, Bichet DG, Brady RO, West M, Germain DP, Wanner C, Waldek S, Clarke JT, Mengel E, Strotmann JM, Warnock DG, Linhart A (2010) A validated disease severity scoring system for Fabry disease. Mol Genet Metab 99(3):283–290
Gold KF, Pastores GM, Botteman MF, Yeh JM, Sweeney S, Aliski W, Pashos CL (2002) Quality of life of patients with Fabry disease. Qual Life Res 11(4):317–327
Hoffmann B, Garcia de Lorenzo A, Mehta A, Beck M, Widmer U, Ricci R (2005) Effects of enzyme replacement therapy on pain and health related quality of life in patients with Fabry disease: data from FOS (Fabry Outcome Survey). J Med Genet 42(3):247–252
Keating GM, Simpson D (2007) Agalsidase Beta: a review of its use in the management of Fabry disease. Drugs 67(3):435–455
Lee K, Jin X, Zhang K, Copertino L, Andrews L, Baker-Malcolm J, Geagan L, Qiu H, Seiger K, Barngrover D, McPherson JM, Edmunds T (2003) A biochemical and pharmacological comparison of enzyme replacement therapies for the glycolipid storage disorder Fabry disease. Glycobiology 13(4):305–313
Linthorst GE, Hollak CE, Donker-Koopman WE, Strijland A, Aerts JM (2004) Enzyme therapy for Fabry disease: neutralizing antibodies toward agalsidase alpha and beta. Kidney Int 66(4):1589–1595
LSDP (2010) Guidelines for the treatment of Fabry Disease through the Life Saving Drugs Program, August 2010
Lubanda JC, Anijalg E, Bzduch V, Thurberg BL, Benichou B, Tylki-Szymanska A (2009) Evaluation of low dose, after a standard therapeutic dose, of agalsidase beta during enzyme replacement therapy in patients with Fabry disease. Genet Med 11(4):256–264
Mehta A, Beck M, Elliott P, Giugliani R, Linhart A, Sunder-Plassmann G, Schiffmann R, Barbey F, Ries M, Clarke JT (2009) Enzyme replacement therapy with agalsidase alfa in patients with Fabry's disease: an analysis of registry data. Lancet 374(9706):1986–1996
Miners AH, Holmes A, Sherr L, Jenkinson C, MacDermot KD (2002) Assessment of health-related quality-of-life in males with Anderson Fabry Disease before therapeutic intervention. Qual Life Res 11(2):127–133
Ohashi T, Sakuma M, Kitagawa T, Suzuki K, Ishige N, Eto Y (2007) Influence of antibody formation on reduction of globotriaosylceramide (GL-3) in urine from Fabry patients during agalsidase beta therapy. Mol Genet Metab 92(3):271–273
Ohashi T, Iizuka S, Ida H, Eto Y (2008) Reduced alpha-Gal A enzyme activity in Fabry fibroblast cells and Fabry mice tissues induced by serum from antibody positive patients with Fabry disease. Mol Genet Metab 94(3):313–318
Pastores GM, Thadhani R (2001) Enzyme-replacement therapy for Anderson-Fabry disease. Lancet 358(9282):601–603
Pastores GM, Boyd E, Crandall K, Whelan A, Piersall L, Barnett N (2007) Safety and pharmacokinetics of agalsidase alfa in patients with Fabry disease and end-stage renal disease. Nephrol Dial Transplant 22(7):1920–1925
Ries M, Clarke JT, Whybra C, Timmons M, Robinson C, Schlaggar BL, Pastores G, Lien YH, Kampmann C, Brady RO, Beck M, Schiffmann R (2006) Enzyme-replacement therapy with agalsidase alfa in children with Fabry disease. Pediatrics 118(3):924–932
Rombach SM, Dekker N, Bouwman MG, Linthorst GE, Zwinderman AH, Wijburg FA, Kuiper S, Vd Bergh Weerman MA, Groener JE, Poorthuis BJ, Hollak CE, Aerts JM (2010) Plasma globotriaosylsphingosine: diagnostic value and relation to clinical manifestations of Fabry disease. Biochim Biophys Acta 1802(9):741–748
Sakuraba H, Murata-Ohsawa M, Kawashima I, Tajima Y, Kotani M, Ohshima T, Chiba Y, Takashiba M, Jigami Y, Fukushige T, Kanzaki T, Itoh K (2006) Comparison of the effects of agalsidase alfa and agalsidase beta on cultured human Fabry fibroblasts and Fabry mice. J Hum Genet 51(3):180–188
Schaefer RM, Tylki-Szymanska A, Hilz MJ (2009) Enzyme replacement therapy for Fabry disease: a systematic review of available evidence. Drugs 69(16):2179–2205
Schiffmann R, Kopp JB, Austin HA III, Sabnis S, Moore DF, Weibel T, Balow JE, Brady RO (2001) Enzyme replacement therapy in Fabry disease: a randomized controlled trial. JAMA 285(21):2743–2749
Schiffmann R, Ries M, Timmons M, Flaherty JT, Brady RO (2006) Long-term therapy with agalsidase alfa for Fabry disease: safety and effects on renal function in a home infusion setting. Nephrol Dial Transplant 21(2):345–354
Schiffmann R, Askari H, Timmons M, Robinson C, Benko W, Brady RO, Ries M (2007) Weekly enzyme replacement therapy may slow decline of renal function in patients with Fabry disease who are on long-term biweekly dosing. J Am Soc Nephrol 18(5):1576–1583
Togawa T, Kodama T, Suzuki T, Sugawara K, Tsukimura T, Ohashi T, Ishige N, Suzuki K, Kitagawa T, Sakuraba H (2010) Plasma globotriaosylsphingosine as a biomarker of Fabry disease. Mol Genet Metab 100(3):257–261
Torra R, Algaba F, Ars E, Santin S, Fernandez-Llama P, Ballarin J (2008) Preservation of renal function in a patient with Fabry nephropathy on enzyme replacement therapy. Clin Nephrol 69(6):445–449
van Breemen MJ, Rombach SM, Dekker N, Poorthuis BJ, Linthorst GE, Zwinderman AH, Breunig F, Wanner C, Aerts JM, Hollak CE (2011) Reduction of elevated plasma globotriaosylsphingosine in patients with classic Fabry disease following enzyme replacement therapy. Biochim Biophys Acta 1812(1):70–76
Vedder AC, Linthorst GE, Houge G, Groener JE, Ormel EE, Bouma BJ, Aerts JM, Hirth A, Hollak CE (2007) Treatment of Fabry disease: outcome of a comparative trial with agalsidase alfa or beta at a dose of 0.2 mg/kg. PLoS One 2(7):e598
Vedder AC, Breunig F, Donker-Koopman WE, Mills K, Young E, Winchester B, Ten Berge IJ, Groener JE, Aerts JM, Wanner C, Hollak CE (2008) Treatment of Fabry disease with different dosing regimens of agalsidase: effects on antibody formation and GL-3. Mol Genet Metab 94(3):319–325
Watt T, Burlina AP, Cazzorla C, Schonfeld D, Banikazemi M, Hopkin RJ, Martins AM, Sims K, Beitner-Johnson D, O'Brien F, Feldt-Rasmussen U (2010) Agalsidase beta treatment is associated with improved quality of life in patients with Fabry disease: findings from the Fabry Registry. Genet Med 12(11):703–712
Whybra C, Kampmann C, Krummenauer F, Ries M, Mengel E, Miebach E, Baehner F, Kim K, Bajbouj M, Schwarting A, Gal A, Beck M (2004) The Mainz Severity Score Index: a new instrument for quantifying the Anderson-Fabry disease phenotype, and the response of patients to enzyme replacement therapy. Clin Genet 65(4):299–307
Whybra C, Miebach E, Mengel E, Gal A, Baron K, Beck M, Kampmann C (2009) A 4-year study of the efficacy and tolerability of enzyme replacement therapy with agalsidase alfa in 36 women with Fabry disease. Genet Med 11(6):441–449
Wilcox WR, Banikazemi M, Guffon N, Waldek S, Lee P, Linthorst GE, Desnick RJ, Germain DP (2004) Long-term safety and efficacy of enzyme replacement therapy for Fabry disease. Am J Hum Genet 75(1):65–74
Young E, Mills K, Morris P, Vellodi A, Lee P, Waldek S, Winchester B (2005) Is globotriaosylceramide a useful biomarker in Fabry disease? Acta Paediatr Suppl 94(447):51–54, discussion 37–58
Acknowledgements
We thank our Fabry disease coordinators and nurse specialists at all Australian treatment centers for their commitment to retrieving data, in maintaining The Fabry Registry and in assisting with this study.
Author information
Authors and Affiliations
Consortia
Corresponding author
Editor information
Editors and Affiliations
Additional information
Communicated by: Frits Wijburg.
Appendices
Synopsis
Australian male Fabry disease patients receiving long-term enzyme replacement therapy (ERT) with Agalsidase beta report reduced energy levels (without a change in disease severity or other quality of life measures) following a 50% reduction in Agalsidase beta dose, as a consequence of the global shortage of this product.
Declarations
All authors have received travel support from Genzyme and/or Shire HGT. Dr Nicholls has received research support from Genzyme and Shire HGT. Dr Fletcher and Prof Sillence have received speaker honoraria from Genzyme. Dr Denaro and Prof Sillence have received coordinator support from Genzyme. Genzyme supports Registry data entry for all centers.
Disclaimer
This paper has been produced with the cooperation of the Australian Government Department of Health and Ageing, which funds and administers the Life Saving Drugs Program (LSDP). The analysis which forms the basis of this paper was conducted by the authors without the use or disclosure of personal information of any patient of the LSDP. Any views expressed or conclusions drawn in the paper are entirely those of the authors and do not reflect any views of the Department or the Australian Government.
Rights and permissions
Copyright information
© 2011 SSIEM and Springer-Verlag Berlin Heidelberg
About this chapter
Cite this chapter
Ghali, J. et al. (2011). Effect of Reduced Agalsidase Beta Dosage in Fabry Patients: The Australian Experience. In: JIMD Reports - Case and Research Reports, 2011/3. JIMD Reports, vol 3. Springer, Berlin, Heidelberg. https://doi.org/10.1007/8904_2011_44
Download citation
DOI: https://doi.org/10.1007/8904_2011_44
Received:
Revised:
Accepted:
Published:
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-642-24935-8
Online ISBN: 978-3-642-24936-5
eBook Packages: MedicineMedicine (R0)