A Randomized Study of Alglucosidase Alfa in Late-Onset Pompe's Disease.

作者：van der Ploeg Ans T^*; Clemens Paula R; Corzo Deyanira; Escolar Diana M; Florence Julaine; Groeneveld Geert Jan; Herson Serge; Kishnani Priya S; Laforet Pascal; Lake Stephen L; Lange Dale J; Leshner Robert T; Mayhew Jill E; Morgan Claire; Nozaki Kenkichi; Park Dorothy J; Pestronk Alan; Rosenbloom Barry; Skrinar Alison; van Capelle Carine I; van der Beek Nadine A; Wasserstein Melissa; Zivkovic Sasa A

来源：New England Journal of Medicine, 2010, 362(15): 1396-1406.

DOI：10.1056/NEJMoa0909859

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.)
N Engl J Med 2010;362:1396-406.

• 出版日期2010-4-15