martes, 26 de septiembre de 2017

Pediatric Research - Early Treatment With Alglucosidase Alfa Prolongs Long-Term Survival of Infants With Pompe Disease

Pediatric Research - Early Treatment With Alglucosidase Alfa Prolongs Long-Term Survival of Infants With Pompe Disease



Early Treatment With Alglucosidase Alfa Prolongs Long-Term Survival of Infants With Pompe Disease

Priya S Kishnani1, Deya Corzo2, Nancy D Leslie3, Daniel Gruskin4, Ans van der Ploeg5, John P Clancy6, Rosella Parini7, Gilles Morin8, Michael Beck9, Mislen S Bauer10, Mikael Jokic11, Chen-En Tsai12, Brian W H Tsai13, Claire Morgan2, Tara O'Meara2, Susan Richards2, Elisa C Tsao2 and Hanna Mandel14
  1. 1Department of Pediatrics, Duke University Medical Center, Durham, North Carolina 27710
  2. 2Department of Clinical Research, Genzyme Corporation, Cambridge, Massachusetts 02142
  3. 3Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229
  4. 4Department of Genetics, Emory University Medical Center, Atlanta, Georgia 30332
  5. 5Division of Metabolic Diseases and Genetics, Erasmus Medical Center, Rotterdam 3015G, The Netherlands
  6. 6Department of Pediatrics, University of Alabama at Birmingham, Birmingham, Alabama 35233
  7. 7Department of Pediatrics, University Milano-Bicocca, Milan 20052, Italy
  8. 8Département de Pédiatrie, CHU Amiens, Amiens 80054, France
  9. 9Metabolic Unit, Universitäts-Kinderklinik Mainz, Mainz 55131, Germany
  10. 10Department of Genetics, Children's Hospital, Miami, Florida 33155
  11. 11Practicien Hospitalier, Réanimation Pédiatrique, Caen 14033, France
  12. 12Tzu-Chi General Hospital, Hua-Lien, Taiwan 970, Republic of China
  13. 13Chi-Mei Foundation Hospital, Yung-Kang City, Taiwan 710, Republic of China
  14. 14Metabolic Unit, Rambam Medical Centre, Haifa 35254, Israel
Correspondence: Priya Sunil Kishnani, MD, Department of Pediatrics-Medical Genetics, Duke University Medical Center, Box 103856 DUMC, 595 LaSalle St. GSRB1, 4th Floor, Durham, NC 27710; e-mail: kishn001@mc.duke.edu
Received 6 February 2009; Accepted 10 April 2009
Supported by the Genzyme Corporation and the Duke Clinical Research Unit Program, National Center for Research Resources, National Institutes of Health (grant number RR024128).Daniel Gruskin is currently at Department of Medical Affairs, Genzyme Corporation, Cambridge, MA 02142.Deya Corzo is currently at Millennium: The Takeda Oncology Company, Cambridge, MA 02139.
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Abstract

In a previous 52-wk trial, treatment with alglucosidase alfa markedly improved cardiomyopathy, ventilatory function, and overall survival among 18 children <7 mo old with infantile-onset Pompe disease. Sixteen of the 18 patients enrolled in an extension study, where they continued to receive alglucosidase alfa at either 20 mg/kg biweekly (n = 8) or 40 mg/kg biweekly (n = 8), for up to a total of 3 y. These children continued to exhibit the benefits of alglucosidase alfa at the age of 36 mo. Cox regression analyses showed that over the entire study period, alglucosidase alfa treatment reduced the risk of death by 95%, reduced the risk of invasive ventilation or death by 91%, and reduced the risk of any type of ventilation or death by 87%, compared with an untreated historical control group. Cardiomyopathy continued to improve and 11 patients learned and sustained substantial motor skills. No significant differences in either safety or efficacy parameters were observed between the 20 and 40 mg/kg biweekly doses. Overall, long-term alglucosidase alfa treatment markedly extended survival as well as ventilation-free survival and improved cardiomyopathy.

Abbreviations: 

AIMS, Alberta Infant Motor Scale; CRIM, cross-reacting immunologic material; GAA, acidα-glucosidase; IAR, infusion-associated reactions; LVM, left ventricular mass; rhGAA, recombinant human acid α-glucosidase

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