A retrospective analysis of the potential impact of IgG antibodies to agalsidase β on efficacy during enzyme replacement therapy for Fabry disease

被引:90
作者
Benichou, Bernard [1 ]
Goyal, Sunita [2 ]
Sung, Crystal [3 ]
Norfleet, Andrea M. [2 ]
O'Brien, Fanny [2 ]
机构
[1] Genzyme Europe, F-78105 St Germain En Laye, France
[2] Genzyme Corp, Cambridge, MA USA
[3] Genzyme Corp, Framingham, MA 01701 USA
关键词
Fabry disease; Agalsidase beta; Lysosomal storage disorder; alpha-Galactosidase A; IgG antibodies; Enzyme replacement therapy; Globotriaosylceramide; X-linked disease; HUMAN ALPHA-GALACTOSIDASE; NEUTRALIZING ANTIBODIES; SAFETY; TRIAL; STORAGE; KIDNEY; GL-3;
D O I
10.1016/j.ymgme.2008.10.004
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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 (R)), 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 1 mg/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. (C) 2008 Elsevier Inc. All rights reserved.
引用
收藏
页码:4 / 12
页数:9
相关论文
共 27 条
[1]   Agalsidase-beta therapy for advanced Fabry disease - A randomized trial [J].
Banikazemi, Maryam ;
Bultas, Jan ;
Waldek, Stephen ;
Wilcox, William R. ;
Whitley, Chester B. ;
McDonald, Marie ;
Finkel, Richard ;
Packman, Seymour ;
Bichet, Daniel G. ;
Warnock, David G. ;
Desnick, Robert J. .
ANNALS OF INTERNAL MEDICINE, 2007, 146 (02) :77-86
[2]   Significance of immune response to enzyme-replacement therapy for patients with a lysosomal storage disorder [J].
Brooks, DA ;
Kakavanos, R ;
Hopwood, JJ .
TRENDS IN MOLECULAR MEDICINE, 2003, 9 (10) :450-453
[3]  
Chapman PB, 2000, CLIN CANCER RES, V6, P874
[4]  
Desnick RobertJ., 2001, The Metabolic and Molecular Bases of Inherited Disease, V8th, P3733
[5]   A phase 1/2 clinical trial of enzyme replacement in Fabry disease: Pharmacokinetic, substrate clearance, and safety studies [J].
Eng, CM ;
Banikazemi, M ;
Gordon, RE ;
Goldman, M ;
Phelps, R ;
Kim, L ;
Gass, A ;
Winston, J ;
Dikman, S ;
Fallon, JT ;
Brodie, S ;
Stacy, CB ;
Mehta, D ;
Parsons, R ;
Norton, K ;
O'Callaghan, M ;
Desnick, RJ .
AMERICAN JOURNAL OF HUMAN GENETICS, 2001, 68 (03) :711-722
[6]   Safety and efficacy of recombinant human α-galactosidase a replacement therapy in Fabry's disease. [J].
Eng, CM ;
Guffon, N ;
Wilcox, WR ;
Germain, DP ;
Lee, P ;
Waldek, S ;
Caplan, L ;
Linthorst, GE ;
Desnick, RJ .
NEW ENGLAND JOURNAL OF MEDICINE, 2001, 345 (01) :9-16
[7]   The molecular defect leading to Fabry disease:: Structure of human α-galactosidase [J].
Garman, SC ;
Garboczi, DN .
JOURNAL OF MOLECULAR BIOLOGY, 2004, 337 (02) :319-335
[8]   Sustained, long-term renal stabilization after 54 months of agalsidase β therapy in patients with Fabry disease [J].
Germain, Dominique P. ;
Waldek, Stephen ;
Banikazemi, Maryam ;
Bushinsky, David A. ;
Charrow, Joel ;
Desnick, Robert J. ;
Lee, Philip ;
Loew, Thomas ;
Vedder, Anouk C. ;
Abichandani, Rekha ;
Wilcox, William R. ;
Guffon, Nathalie .
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, 2007, 18 (05) :1547-1557
[9]   Neutralizing antibodies to interferon beta in patients with multiple sclerosis: scientific background and clinical implications - Introduction [J].
Hartung, HP ;
Schellekens, H ;
Munschauer, FE .
JOURNAL OF NEUROLOGY, 2004, 251 (Suppl 2) :1-3
[10]   Late abnormal findings on high-resolution computed tomography after Mycoplasma pneumonia [J].
Kim, CK ;
Chung, CY ;
Kim, JS ;
Kim, WS ;
Park, Y ;
Koh, YY .
PEDIATRICS, 2000, 105 (02) :372-378