Clinical outcomes after long-term treatment with alglucosidase alfa in infants and children with advanced Pompe disease

被引：230

作者：

Nicolino, Marc ^{[2
]}

Byrne, Barrv ^{[3
]}

Wraith, J. Edmund ^{[4
]}

Leslie, Nancy ^{[5
]}

Mandel, Hanna ^{[6
]}

Freyer, David R. ^{[7
]}

Arnold, Georgianne L. ^{[8
]}

Pivnick, Eniko K. ^{[9
]}

Ottinger, C. J. ^{[10
]}

Robinson, Peter H. ^{[11
]}

Loo, John-Charles A. ^{[12
]}

Smitka, Martin ^{[13
]}

Jardine, Philip ^{[14
]}

Tato, Luciano ^{[15
]}

Chabrol, Brigitte ^{[16
]}

McCandless, Shawn ^{[17
]}

Kimura, Shigenzi ^{[18
]}

Mehta, L. ^{[19
]}

Bali, Deeksha ^{[20
]}

Skrinar, Alison ^{[21
]}

Morgan, Claire ^{[21
]}

Rangachari, Lakshmi ^{[21
]}

Corzo, Deya ^{[22
]}

Kishnani, Priya S. ^{[1
,20
]}

机构：

[1] Duke Univ, Med Ctr, Dept Pediat, Div Med Genet, Durham, NC 27710 USA

[2] Univ Lyon, Div Pediat Endocrinol Diabetol & Metab, Hop Debrousse, Lyon, France

[3] Univ Florida, Shands Hosp, Gainesville, FL USA

[4] Royal Manchester Childrens Hosp, Manchester M27 1HA, Lancs, England

[5] Cincinnati Childrens Hosp, Med Ctr, Cincinnati, OH USA

[6] Rambam Med Ctr, Haifa, Israel

[7] DeVos Childrens Hosp, Grand Rapids, MI USA

[8] Univ Rochester, Med Ctr, Rochester, NY 14642 USA

[9] Univ Tennessee, Ctr Hlth Sci, Memphis, TN 38163 USA

[10] Ft Wayne Neurol Ctr, Ft Wayne, IN USA

[11] Royal Hosp Sick Children, Edinburgh EH9 1LF, Midlothian, Scotland

[12] Long Beach Mem Med Ctr, Long Beach, CA USA

[13] Tech Univ Dresden, Dresden, Germany

[14] Bristol Royal Hosp Children, Bristol, Avon, England

[15] Univ Verona, I-37100 Verona, Italy

[16] Hop Enfants La Timone, Marseille, France

[17] Univ Hosp Cleveland, Cleveland, OH 44106 USA

[18] Kumamoto Univ, Sch Med, Kumamoto 860, Japan

[19] Mt Sinai Med Ctr, New York, NY 10029 USA

[20] Duke Univ, Med Ctr, Durham, NC USA

[21] Genzyme Corp, Cambridge, MA USA

[22] Millennium Pharmaceut Inc, Cambridge, MA USA

来源：

GENETICS IN MEDICINE | 2009年 / 11卷 / 03期

关键词：

Pompe disease; glycogen storage disease type II; acid maltase deficiency; Myozyme; alglucosidase alfa; lysosomal acid alpha-glucosidase; recombinant human GAA; enzyme replacement therapy; cardiomyopathy; motor development; BECKWITH-WIEDEMANN-SYNDROME; ISOLATED HEMIHYPERPLASIA; IDIOPATHIC HEMIHYPERTROPHY; WILMS-TUMOR; FETOPROTEIN; RISK;

D O I：

10.1097/GIM.0b013e31819d0996

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Purpose: A clinical trial was conducted to evaluate the safety and efficacy of alglucosidase alfa in infants and children with advanced Pompe disease. Methods: Open-label, multicenter study of IV alglucosidase alfa treatment in 21 infants 3-43 months old (median 13 months) with minimal acid a-glucosidase activity and abnormal left ventricular mass index by echo-cardiography. Patients received IV alglucosidase alfa every 2 weeks for up to 168 weeks (median 120 weeks). Survival results were compared with tin untreated reference cohort. Results: At study end, 71% (15/21) of patients were alive and 44% (7/16) of invasive-ventilator free patients remained so. Compared with the untreated reference cohort, alglucosidase alfa reduced the risk of death by 79% (P < 0.001) and the risk of invasive ventilation by 58% (P = 0.02). Left ventricular mass index improved or remained normal in all patients evaluated beyond 12 weeks; 62% (13/21) achieved new motor milestones. Five patients were walking independently at the end of the study and 86% (18/21) gained functional independence skills. Overall, 52% (11/21) of patients experienced infusion-associated reactions; 95% (19/20) developed IgG antibodies to recombinant human lysosomal acid a-glucosidase; no patients withdrew from the study because of safety concerns. Conclusions: In this population of infants with advanced disease, biweekly infusions with alglucosidase alfa prolonged survival and invasive ventilation-flee survival. Treatment also improved indices of cardiomyopathy, motor skills, and functional independence. Genet Med 2009:11(3):210-219.

引用

页码：210 / 222

页数：13

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