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A randomized study of alglucosidase alfa in late-onset Pompe's disease.
N Engl J Med. 2010 Apr 15; 362(15):1396-406.NEJM

Abstract

BACKGROUND

Pompe's disease is a metabolic myopathy caused by a deficiency of acid alpha glucosidase (GAA), an enzyme that degrades lysosomal glycogen. Late-onset Pompe's disease is characterized by progressive muscle weakness and loss of respiratory function, leading to early death. We conducted a randomized, placebo-controlled trial of alglucosidase alfa, a recombinant human GAA, for the treatment of late-onset Pompe's disease.

METHODS

Ninety patients who were 8 years of age or older, ambulatory, and free of invasive ventilation were randomly assigned to receive biweekly intravenous alglucosidase alfa (20 mg per kilogram of body weight) or placebo for 78 weeks at eight centers in the United States and Europe. The two primary end points were distance walked during a 6-minute walk test and percentage of predicted forced vital capacity (FVC).

RESULTS

At 78 weeks, the estimated mean changes from baseline in the primary end points favored alglucosidase alfa (an increase of 28.1+/-13.1 m on the 6-minute walk test and an absolute increase of 3.4+/-1.2 percentage points in FVC; P=0.03 and P=0.006, respectively). Similar proportions of patients in the two groups had adverse events, serious adverse events, and infusion-associated reactions; events that occurred only in patients who received the active study drug included anaphylactic reactions and infusion-associated reactions of urticaria, flushing, hyperhidrosis, chest discomfort, vomiting, and increased blood pressure (each of which occurred in 5 to 8% of the patients).

CONCLUSIONS

In this study population, treatment with alglucosidase alfa was associated with improved walking distance and stabilization of pulmonary function over an 18-month period. (ClinicalTrials.gov number, NCT00158600.)

Authors+Show Affiliations

Department of Pediatrics, Center for Lysosomal and Metabolic Diseases, Erasmus MC University Medical Center, Rotterdam, The Netherlands. a.vanderploeg@erasmusmc.nlNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20393176

Citation

van der Ploeg, Ans T., et al. "A Randomized Study of Alglucosidase Alfa in Late-onset Pompe's Disease." The New England Journal of Medicine, vol. 362, no. 15, 2010, pp. 1396-406.
van der Ploeg AT, Clemens PR, Corzo D, et al. A randomized study of alglucosidase alfa in late-onset Pompe's disease. N Engl J Med. 2010;362(15):1396-406.
van der Ploeg, A. T., Clemens, P. R., Corzo, D., Escolar, D. M., Florence, J., Groeneveld, G. J., Herson, S., Kishnani, P. S., Laforet, P., Lake, S. L., Lange, D. J., Leshner, R. T., Mayhew, J. E., Morgan, C., Nozaki, K., Park, D. J., Pestronk, A., Rosenbloom, B., Skrinar, A., ... Zivkovic, S. A. (2010). A randomized study of alglucosidase alfa in late-onset Pompe's disease. The New England Journal of Medicine, 362(15), 1396-406. https://doi.org/10.1056/NEJMoa0909859
van der Ploeg AT, et al. A Randomized Study of Alglucosidase Alfa in Late-onset Pompe's Disease. N Engl J Med. 2010 Apr 15;362(15):1396-406. PubMed PMID: 20393176.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A randomized study of alglucosidase alfa in late-onset Pompe's disease. AU - van der Ploeg,Ans T, AU - Clemens,Paula R, AU - Corzo,Deyanira, AU - Escolar,Diana M, AU - Florence,Julaine, AU - Groeneveld,Geert Jan, AU - Herson,Serge, AU - Kishnani,Priya S, AU - Laforet,Pascal, AU - Lake,Stephen L, AU - Lange,Dale J, AU - Leshner,Robert T, AU - Mayhew,Jill E, AU - Morgan,Claire, AU - Nozaki,Kenkichi, AU - Park,Dorothy J, AU - Pestronk,Alan, AU - Rosenbloom,Barry, AU - Skrinar,Alison, AU - van Capelle,Carine I, AU - van der Beek,Nadine A, AU - Wasserstein,Melissa, AU - Zivkovic,Sasa A, PY - 2010/4/16/entrez PY - 2010/4/16/pubmed PY - 2010/4/23/medline SP - 1396 EP - 406 JF - The New England journal of medicine JO - N. Engl. J. Med. VL - 362 IS - 15 N2 - BACKGROUND: Pompe's disease is a metabolic myopathy caused by a deficiency of acid alpha glucosidase (GAA), an enzyme that degrades lysosomal glycogen. Late-onset Pompe's disease is characterized by progressive muscle weakness and loss of respiratory function, leading to early death. We conducted a randomized, placebo-controlled trial of alglucosidase alfa, a recombinant human GAA, for the treatment of late-onset Pompe's disease. METHODS: Ninety patients who were 8 years of age or older, ambulatory, and free of invasive ventilation were randomly assigned to receive biweekly intravenous alglucosidase alfa (20 mg per kilogram of body weight) or placebo for 78 weeks at eight centers in the United States and Europe. The two primary end points were distance walked during a 6-minute walk test and percentage of predicted forced vital capacity (FVC). RESULTS: At 78 weeks, the estimated mean changes from baseline in the primary end points favored alglucosidase alfa (an increase of 28.1+/-13.1 m on the 6-minute walk test and an absolute increase of 3.4+/-1.2 percentage points in FVC; P=0.03 and P=0.006, respectively). Similar proportions of patients in the two groups had adverse events, serious adverse events, and infusion-associated reactions; events that occurred only in patients who received the active study drug included anaphylactic reactions and infusion-associated reactions of urticaria, flushing, hyperhidrosis, chest discomfort, vomiting, and increased blood pressure (each of which occurred in 5 to 8% of the patients). CONCLUSIONS: In this study population, treatment with alglucosidase alfa was associated with improved walking distance and stabilization of pulmonary function over an 18-month period. (ClinicalTrials.gov number, NCT00158600.) SN - 1533-4406 UR - https://www.unboundmedicine.com/medline/citation/20393176/A_randomized_study_of_alglucosidase_alfa_in_late_onset_Pompe's_disease_ L2 - http://www.nejm.org/doi/full/10.1056/NEJMoa0909859?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -