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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. 2009 Jan; 96(1):4-12.MG

Abstract

Fabry disease results from a genetic deficiency of alpha-galactosidase A (alpha GAL) and the impaired catabolism of globotriasoylceramide (GL-3) and other glycosphingolipid substrates, which then accumulate pathogenically within most cells. Enzyme replacement therapy (ERT) with agalsidase beta (Fabrazyme), one of two available forms of recombinant human alpha GAL, involves regular intravenous infusions of the therapeutic protein. Immunoglobulin G (IgG) antibodies to recombinant alpha GAL develop in the majority of patients upon repeated infusion. To explore whether anti-alpha GAL IgG interferes with therapeutic efficacy, retrospective analyses were conducted using data obtained from a total of 134 adult male and female patients with Fabry disease who were treated with agalsidase beta at 1mg/kg every 2 weeks for up to 5 years during placebo-controlled trials and the corresponding open-label extension studies. The analyses did not reveal a correlation between anti-alpha GAL IgG titers and the onset of clinical events or the rate of change in estimated GFR during treatment, and no statistically significant association was found between anti-alpha GAL IgG titers and abnormal elevations in plasma GL-3 during treatment. However, a statistically significant association was found between anti-alpha GAL IgG titers and observation of some GL-3 deposition in the dermal capillary endothelial cells of skin during treatment, suggesting that GL-3 clearance may be partially impaired in some patients with high antibody titers. Determination of the long-term impact of circulating anti-alpha GAL IgG antibodies on clinical outcomes will require continued monitoring, and serology testing is recommended as part of the routine care of Fabry disease patients during ERT.

Authors+Show Affiliations

Genzyme Europe, 33-35 Bd de la Paix, Parc d'activités du Bel-Air, 78105 Saint-Germain-en-Laye Cedex, France. bernard.benichou@genzyme.comNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial, Phase III
Clinical Trial, Phase IV
Journal Article
Randomized Controlled Trial

Language

eng

PubMed ID

19022694

Citation

Bénichou, Bernard, et al. "A Retrospective Analysis of the Potential Impact of IgG Antibodies to Agalsidase Beta On Efficacy During Enzyme Replacement Therapy for Fabry Disease." Molecular Genetics and Metabolism, vol. 96, no. 1, 2009, pp. 4-12.
Bénichou B, Goyal S, Sung C, et al. 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. 2009;96(1):4-12.
Bénichou, B., Goyal, S., Sung, C., Norfleet, A. M., & 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. Molecular Genetics and Metabolism, 96(1), 4-12. https://doi.org/10.1016/j.ymgme.2008.10.004
Bénichou B, et al. 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. 2009;96(1):4-12. PubMed PMID: 19022694.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A retrospective analysis of the potential impact of IgG antibodies to agalsidase beta on efficacy during enzyme replacement therapy for Fabry disease. AU - Bénichou,Bernard, AU - Goyal,Sunita, AU - Sung,Crystal, AU - Norfleet,Andrea M, AU - O'Brien,Fanny, Y1 - 2008/11/20/ PY - 2008/10/08/received PY - 2008/10/08/accepted PY - 2008/11/22/pubmed PY - 2009/1/22/medline PY - 2008/11/22/entrez SP - 4 EP - 12 JF - Molecular genetics and metabolism JO - Mol Genet Metab VL - 96 IS - 1 N2 - Fabry disease results from a genetic deficiency of alpha-galactosidase A (alpha GAL) and the impaired catabolism of globotriasoylceramide (GL-3) and other glycosphingolipid substrates, which then accumulate pathogenically within most cells. Enzyme replacement therapy (ERT) with agalsidase beta (Fabrazyme), one of two available forms of recombinant human alpha GAL, involves regular intravenous infusions of the therapeutic protein. Immunoglobulin G (IgG) antibodies to recombinant alpha GAL develop in the majority of patients upon repeated infusion. To explore whether anti-alpha GAL IgG interferes with therapeutic efficacy, retrospective analyses were conducted using data obtained from a total of 134 adult male and female patients with Fabry disease who were treated with agalsidase beta at 1mg/kg every 2 weeks for up to 5 years during placebo-controlled trials and the corresponding open-label extension studies. The analyses did not reveal a correlation between anti-alpha GAL IgG titers and the onset of clinical events or the rate of change in estimated GFR during treatment, and no statistically significant association was found between anti-alpha GAL IgG titers and abnormal elevations in plasma GL-3 during treatment. However, a statistically significant association was found between anti-alpha GAL IgG titers and observation of some GL-3 deposition in the dermal capillary endothelial cells of skin during treatment, suggesting that GL-3 clearance may be partially impaired in some patients with high antibody titers. Determination of the long-term impact of circulating anti-alpha GAL IgG antibodies on clinical outcomes will require continued monitoring, and serology testing is recommended as part of the routine care of Fabry disease patients during ERT. SN - 1096-7206 UR - https://www.unboundmedicine.com/medline/citation/19022694/A_retrospective_analysis_of_the_potential_impact_of_IgG_antibodies_to_agalsidase_beta_on_efficacy_during_enzyme_replacement_therapy_for_Fabry_disease_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1096-7192(08)00254-0 DB - PRIME DP - Unbound Medicine ER -