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Safety and effectiveness of enzyme replacement therapy with agalsidase alfa in patients with Fabry disease: Post-marketing surveillance in Japan.
Mol Genet Metab. 2019 04; 126(4):448-459.MG

Abstract

Fabry disease is a rare X-linked inherited multisystem disorder resulting from deficiency of the lysosomal enzyme alpha-galactosidase A. Currently, specific therapies, including enzyme replacement therapies, are available for Fabry disease, but clinical trials provide limited information on long-term safety and effectiveness. Agalsidase alfa was approved in Japan in 2006. The post-marketing surveillance study of all patients receiving agalsidase alfa to evaluate its long-term safety and effectiveness as a mandatory condition for its approval had been conducted for 8 years (from February 2007 to March 2015). A total of 493 patients were included in this analysis of safety and effectiveness. The overall mean follow-up period was 3.5 years (range, 0.0-7.9 years). The percentage of patients with adverse drug reactions was 24.5% (121/493) and 12.6% had infusion-related reactions (62/493). In the 256 patients without prior enzyme replacement therapy whose IgG antibody data were available, 17 were IgG antibody positive (6.6%). However, the chronological correlation between seroconversion and the incidence of infusion-related reactions was not clear. The mean brief pain inventory score of the worst pain decreased in patients with moderate and severe pain at baseline. Plasma Gb3 and urine sediment Gb3 in males with classical Fabry disease without prior enzyme replacement therapy significantly decreased. The mean yearly changes in eGFR (mL/min/1.73 m2) ranged from -2.88 to +1.00 in males with classical Fabry disease, from -2.04 to -0.95 in males with non-typical variant and from -2.64 to -1.02 in females. The lower eGFR or the more proteinuria at baseline, the faster the decrease in eGFR of the patients was observed. There was no substantial difference in cardiac parameters (left ventricular mass index, E/A wave ratio, ejection fraction, and QRS duration). In conclusion, agalsidase alfa, 0.2 mg/kg every other week, was well tolerated and controlled the progression of symptoms (especially renal and cardiac) of Fabry disease in adults. Enzyme replacement therapy should be started in Japanese patients before cardiac and/or renal symptoms of Fabry disease develop.

Authors+Show Affiliations

Sumitomo Dainippon Pharma Co., Ltd., Osaka, Japan. Electronic address: hiroaki-sasa@ds-pharma.co.jp.Sumitomo Dainippon Pharma Co., Ltd., Osaka, Japan.Sumitomo Dainippon Pharma Co., Ltd., Osaka, Japan.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

30803893

Citation

Sasa, Hiroaki, et al. "Safety and Effectiveness of Enzyme Replacement Therapy With Agalsidase Alfa in Patients With Fabry Disease: Post-marketing Surveillance in Japan." Molecular Genetics and Metabolism, vol. 126, no. 4, 2019, pp. 448-459.
Sasa H, Nagao M, Kino K. Safety and effectiveness of enzyme replacement therapy with agalsidase alfa in patients with Fabry disease: Post-marketing surveillance in Japan. Mol Genet Metab. 2019;126(4):448-459.
Sasa, H., Nagao, M., & Kino, K. (2019). Safety and effectiveness of enzyme replacement therapy with agalsidase alfa in patients with Fabry disease: Post-marketing surveillance in Japan. Molecular Genetics and Metabolism, 126(4), 448-459. https://doi.org/10.1016/j.ymgme.2019.02.005
Sasa H, Nagao M, Kino K. Safety and Effectiveness of Enzyme Replacement Therapy With Agalsidase Alfa in Patients With Fabry Disease: Post-marketing Surveillance in Japan. Mol Genet Metab. 2019;126(4):448-459. PubMed PMID: 30803893.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Safety and effectiveness of enzyme replacement therapy with agalsidase alfa in patients with Fabry disease: Post-marketing surveillance in Japan. AU - Sasa,Hiroaki, AU - Nagao,Munehiko, AU - Kino,Koichi, Y1 - 2019/02/20/ PY - 2018/10/19/received PY - 2019/02/19/revised PY - 2019/02/19/accepted PY - 2019/2/26/pubmed PY - 2019/11/8/medline PY - 2019/2/27/entrez KW - Agalsidase alfa KW - Enzyme replacement therapy (ERT) KW - Fabry disease KW - Post-marketing surveillance SP - 448 EP - 459 JF - Molecular genetics and metabolism JO - Mol. Genet. Metab. VL - 126 IS - 4 N2 - Fabry disease is a rare X-linked inherited multisystem disorder resulting from deficiency of the lysosomal enzyme alpha-galactosidase A. Currently, specific therapies, including enzyme replacement therapies, are available for Fabry disease, but clinical trials provide limited information on long-term safety and effectiveness. Agalsidase alfa was approved in Japan in 2006. The post-marketing surveillance study of all patients receiving agalsidase alfa to evaluate its long-term safety and effectiveness as a mandatory condition for its approval had been conducted for 8 years (from February 2007 to March 2015). A total of 493 patients were included in this analysis of safety and effectiveness. The overall mean follow-up period was 3.5 years (range, 0.0-7.9 years). The percentage of patients with adverse drug reactions was 24.5% (121/493) and 12.6% had infusion-related reactions (62/493). In the 256 patients without prior enzyme replacement therapy whose IgG antibody data were available, 17 were IgG antibody positive (6.6%). However, the chronological correlation between seroconversion and the incidence of infusion-related reactions was not clear. The mean brief pain inventory score of the worst pain decreased in patients with moderate and severe pain at baseline. Plasma Gb3 and urine sediment Gb3 in males with classical Fabry disease without prior enzyme replacement therapy significantly decreased. The mean yearly changes in eGFR (mL/min/1.73 m2) ranged from -2.88 to +1.00 in males with classical Fabry disease, from -2.04 to -0.95 in males with non-typical variant and from -2.64 to -1.02 in females. The lower eGFR or the more proteinuria at baseline, the faster the decrease in eGFR of the patients was observed. There was no substantial difference in cardiac parameters (left ventricular mass index, E/A wave ratio, ejection fraction, and QRS duration). In conclusion, agalsidase alfa, 0.2 mg/kg every other week, was well tolerated and controlled the progression of symptoms (especially renal and cardiac) of Fabry disease in adults. Enzyme replacement therapy should be started in Japanese patients before cardiac and/or renal symptoms of Fabry disease develop. SN - 1096-7206 UR - https://www.unboundmedicine.com/medline/citation/30803893/Safety_and_effectiveness_of_enzyme_replacement_therapy_with_agalsidase_alfa_in_patients_with_Fabry_disease:_Post_marketing_surveillance_in_Japan_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1096-7192(18)30651-6 DB - PRIME DP - Unbound Medicine ER -