Anti-alpha-galactosidase A antibody response to agalsidase beta treatment: Data from the Fabry Registry

作者：Wilcox William R^*; Linthorst Gabor E; Germain Dominique P; Feldt Rasmussen Ulla; Waldek Stephen; Richards Susan M; Beitner Johnson Dana; Cizmarik Marta; Cole J Alexander; Kingma Wytske; Warnock David G

来源：Molecular Genetics and Metabolism, 2012, 105(3): 443-449.

DOI：10.1016/j.ymgme.2011.12.006

• Fabry disease
• Lysosomal storage diseases
• Alpha-galactosidase
• Enzyme replacement therapy
• Glycosphingolipids
• Antibody formation

Agalsidase beta, a form of recombinant human alpha-galactosidase A (alpha GAL), is approved for use as enzyme replacement therapy (ERT) for Fabry disease. An immunogenic response against a therapeutic protein could potentially impact its efficacy or safety. The development of anti-alpha GAL IgG antibodies was evaluated in 571 men and 251 women from the Fabry Registry who were treated with agalsidase beta. Most men developed antibodies (416 of 571, 73%), whereas most women did not (31 of 251, 12%). Women were also significantly more likely to tolerize than men; whereas 18 of 31 women tolerized (58%, 95%Cl: 52%-64%), only 47 of 416 men tolerized during the observation period (11%, 95% Cl; 8%-15%). Patients who eventually tolerized had lower median peak anti-alpha GAL IgG antibody titers than patients who remained seropositive at their most recent assessment (400 versus 3200 in men, 200 versus 400 in women, respectively). Patients with nonsense mutations in the GM gene were more likely to develop anti-alpha GAL IgG antibodies than patients with missense mutations. Approximately 26% of men (151 of 571) reported infusion-associated reactions (IARs), compared to 11% of women (27 of 251). Men who developed anti-alpha GAL IgG antibodies were more likely to experience IARs compared to those who remained seronegative. Nine percent of seronegative men and women (34 of 375) reported IARs. The majority of IARs occurred during the first 6 to 12 months of agalsidase beta treatment and decreased over time, in both seroconvertecl and seronegative patients.

• 出版日期2012-3
• 单位河北医科大学