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Effects of a higher dose of alglucosidase alfa on ventilator-free survival and motor outcome in classic infantile Pompe disease: an open-label single-center study.
J Inherit Metab Dis 2016; 39(3):383-390JI

Abstract

BACKGROUND

Though enzyme-replacement therapy (ERT) with alglucosidase alfa has significantly improved the prospects for patients with classic infantile Pompe disease, some 50 % of treated infants do not survive ventilator-free beyond the age of 3 years. We investigated whether higher and more frequent dosing of alglucosidase alfa improves outcome.

METHODS

Eight cross-reactive immunological material (CRIM) positive patients were included in the study. All had fully deleterious mutations in both GAA alleles. Four received a dose of 20 mg/kg every other week (eow) and four received 40 mg/kg/week. Survival, ventilator-free survival, left-ventricular mass index (LVMI), motor outcome, infusion-associated reactions (IARs), and antibody formation were evaluated.

RESULTS

All eight patients were alive at study end, seven of them remained ventilator-free. The patient who became ventilator dependent was treated with 20 mg/kg eow. Three of the four patients receiving 20 mg/kg eow learned to walk; two of them maintained this ability at study end. All four patients receiving 40 mg/kg/week acquired and maintained the ability to walk at study end (ages of 3.3-5.6 years), even though their baseline motor functioning was poorer. There were no apparent differences between the two dose groups with respect to the effect of ERT on LVMI, the number of IARs and antibody formation.

CONCLUSIONS

Our data may suggest that a dose of 40 mg/kg/week improves outcome of CRIM positive patients over that brought by the currently recommended dose of 20 mg/kg eow. Larger studies are needed to draw definite conclusions.

Authors+Show Affiliations

Department of Pediatrics, Division of Metabolic Diseases and Genetics, Center for Lysosomal and Metabolic Diseases, Erasmus MC University Medical Center, Dr Molewaterplein 60, 3015 GJ, Rotterdam, The Netherlands.Department of Pediatrics, Division of Metabolic Diseases and Genetics, Center for Lysosomal and Metabolic Diseases, Erasmus MC University Medical Center, Dr Molewaterplein 60, 3015 GJ, Rotterdam, The Netherlands.Department of Pediatrics, Division of Metabolic Diseases and Genetics, Center for Lysosomal and Metabolic Diseases, Erasmus MC University Medical Center, Dr Molewaterplein 60, 3015 GJ, Rotterdam, The Netherlands.Department of Clinical Genetics, Center for Lysosomal and Metabolic Diseases, Erasmus MC University Medical Center, Rotterdam, The Netherlands.Department of Pediatrics, Division of Metabolic Diseases and Genetics, Center for Lysosomal and Metabolic Diseases, Erasmus MC University Medical Center, Dr Molewaterplein 60, 3015 GJ, Rotterdam, The Netherlands. Department of Neurology, Center for Lysosomal and Metabolic Diseases, Erasmus MC University Medical Center, Rotterdam, The Netherlands.Department of Clinical Genetics, Center for Lysosomal and Metabolic Diseases, Erasmus MC University Medical Center, Rotterdam, The Netherlands.Department of Pediatrics, Division of Metabolic Diseases and Genetics, Center for Lysosomal and Metabolic Diseases, Erasmus MC University Medical Center, Dr Molewaterplein 60, 3015 GJ, Rotterdam, The Netherlands. a.vanderploeg@erasmusmc.nl.

Pub Type(s)

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

Language

eng

PubMed ID

26768149

Citation

van Gelder, C M., et al. "Effects of a Higher Dose of Alglucosidase Alfa On Ventilator-free Survival and Motor Outcome in Classic Infantile Pompe Disease: an Open-label Single-center Study." Journal of Inherited Metabolic Disease, vol. 39, no. 3, 2016, pp. 383-390.
van Gelder CM, Poelman E, Plug I, et al. Effects of a higher dose of alglucosidase alfa on ventilator-free survival and motor outcome in classic infantile Pompe disease: an open-label single-center study. J Inherit Metab Dis. 2016;39(3):383-390.
van Gelder, C. M., Poelman, E., Plug, I., Hoogeveen-Westerveld, M., van der Beek, N. A. M. E., Reuser, A. J. J., & van der Ploeg, A. T. (2016). Effects of a higher dose of alglucosidase alfa on ventilator-free survival and motor outcome in classic infantile Pompe disease: an open-label single-center study. Journal of Inherited Metabolic Disease, 39(3), pp. 383-390. doi:10.1007/s10545-015-9912-y.
van Gelder CM, et al. Effects of a Higher Dose of Alglucosidase Alfa On Ventilator-free Survival and Motor Outcome in Classic Infantile Pompe Disease: an Open-label Single-center Study. J Inherit Metab Dis. 2016;39(3):383-390. PubMed PMID: 26768149.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effects of a higher dose of alglucosidase alfa on ventilator-free survival and motor outcome in classic infantile Pompe disease: an open-label single-center study. AU - van Gelder,C M, AU - Poelman,E, AU - Plug,I, AU - Hoogeveen-Westerveld,M, AU - van der Beek,N A M E, AU - Reuser,A J J, AU - van der Ploeg,A T, Y1 - 2016/01/14/ PY - 2015/06/05/received PY - 2015/12/18/accepted PY - 2015/12/17/revised PY - 2016/1/16/entrez PY - 2016/1/16/pubmed PY - 2017/12/8/medline SP - 383 EP - 390 JF - Journal of inherited metabolic disease JO - J. Inherit. Metab. Dis. VL - 39 IS - 3 N2 - BACKGROUND: Though enzyme-replacement therapy (ERT) with alglucosidase alfa has significantly improved the prospects for patients with classic infantile Pompe disease, some 50 % of treated infants do not survive ventilator-free beyond the age of 3 years. We investigated whether higher and more frequent dosing of alglucosidase alfa improves outcome. METHODS: Eight cross-reactive immunological material (CRIM) positive patients were included in the study. All had fully deleterious mutations in both GAA alleles. Four received a dose of 20 mg/kg every other week (eow) and four received 40 mg/kg/week. Survival, ventilator-free survival, left-ventricular mass index (LVMI), motor outcome, infusion-associated reactions (IARs), and antibody formation were evaluated. RESULTS: All eight patients were alive at study end, seven of them remained ventilator-free. The patient who became ventilator dependent was treated with 20 mg/kg eow. Three of the four patients receiving 20 mg/kg eow learned to walk; two of them maintained this ability at study end. All four patients receiving 40 mg/kg/week acquired and maintained the ability to walk at study end (ages of 3.3-5.6 years), even though their baseline motor functioning was poorer. There were no apparent differences between the two dose groups with respect to the effect of ERT on LVMI, the number of IARs and antibody formation. CONCLUSIONS: Our data may suggest that a dose of 40 mg/kg/week improves outcome of CRIM positive patients over that brought by the currently recommended dose of 20 mg/kg eow. Larger studies are needed to draw definite conclusions. SN - 1573-2665 UR - https://www.unboundmedicine.com/medline/citation/26768149/Effects_of_a_higher_dose_of_alglucosidase_alfa_on_ventilator_free_survival_and_motor_outcome_in_classic_infantile_Pompe_disease:_an_open_label_single_center_study_ L2 - https://doi.org/10.1007/s10545-015-9912-y DB - PRIME DP - Unbound Medicine ER -