Motor Responses in Pediatric Pompe Disease in the ADVANCE Participant Cohort

Authors

Tina Duong, Department of Neurology, Division of Neuromuscular Medicine, Stanford University School of Medicine, Palo Alto, CA, USA.
Priya S. Kishnani, Department of Pediatrics, Duke University Medical Center, Durham, NC, USA.
Kristina An Haack, Sanofi, Chilly-Mazarin, France.Follow
Meredith C. Foster, Sanofi, Cambridge, MA, USA.
James B. Gibson, Clinical and Metabolic Genetics, Dell Children's Medical Group, Austin, TX, USA.
Catherine Wilson, Sanofi, Cambridge, MA, USA.
Si Houn Hahn, Departments of Pediatrics and Medicine and Biochemical Genetics Program, Seattle Children's Hospital/University of Washington, Seattle, WA, USA.
Richard Hillman, University of Missouri Child Health, Columbia, MO, USA.
David Kronn, Departments of Pathology and Pediatrics, New York Medical College, Valhalla, NY, USA.Follow
Nancy D. Leslie, Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Loren D. Peña, Department of Pediatrics, Duke University Medical Center, Durham, NC, USA.
Susan E. Sparks, Sanofi, Cambridge, MA, USA.
David W. Stockton, Division of Genetic, Genomic, and Metabolic Disorders, Central Michigan University and Children's Hospital of Michigan, Detroit, MI, USA.
Pranoot Tanpaiboon, Rare Disease Institute, Children's National Hospital, Washington, DC, USA.
John W. Day, Department of Neurology, Division of Neuromuscular Medicine, Stanford University School of Medicine, Palo Alto, CA, USA.

Author Type(s)

Faculty

DOI

10.3233/JND-210784

Journal Title

Journal of Neuromuscular Diseases

First Page

713

Last Page

730

Document Type

Article

Publication Date

1-1-2022

Department

Pediatrics

Abstract

BACKGROUND: ADVANCE (NCT01526785) presented an opportunity to obtain a more nuanced understanding of motor function changes in treatment-experienced children with Pompe disease receiving 4000L-production-scale alglucosidase alfa for 52 weeks. OBJECTIVE: To estimate minimal detectable change (MDC) and effect size on Gross Motor Function Measure-88 (GMFM-88) after 52 weeks of 4000L alglucosidase alfa (complete data N =  90). METHODS: The GMFM-88 mean total % score changes, MDC, and effect size were analyzed post hoc by Pompe Motor Function Level at enrollment, age groups at enrollment, and fraction of life on pre-study 160L-production-scale alglucosidase alfa. RESULTS: Overall, participants aged < 2 years surpassed MDC at Week 52 (change [mean±standard deviation] 21.1±14.1, MDC range 5.7-13.3, effect size 1.1), whereas participants aged≥2 years did not attain this (change -0.9±15.3, MDC range 10.8-25.2, effect size -0.03). In participants aged < 2 years, improvements surpassed the MDC for walkers (change 17.1±13.3, MDC range 3.0-6.9, effect size 1.7), supported standers (change 35.2±18.0, MDC range 5.9-13.7, effect size 1.8) and sitters (change 24.1±12.1, MDC range 2.6-6.2, effect size 2.7). Age-independent MDC ranges were only attained by walkers (change 7.7±12.3, MDC range 6.4-15.0, effect size 0.4) and sitters (change 9.9±17.2, MDC range 3.3-7.7, effect size 0.9). CONCLUSIONS: These first GMFM-88 minimal-detectable-change estimates for alglucosidase alfa-treated Pompe disease offer utility for monitoring motor skills. TRIAL REGISTRATION: ClinicalTrials.gov; NCT01526785; Registered 6 February 2012; https://clinicaltrials.gov/ct2/show/NCT01526785.

Recommended Citation

Duong, T., Kishnani, P. S., An Haack, K., Foster, M. C., Gibson, J. B., Wilson, C., Hahn, S. H., Hillman, R., Kronn, D., Leslie, N. D., Peña, L. D., Sparks, S. E., Stockton, D. W., Tanpaiboon, P., & Day, J. W. (2022). Motor Responses in Pediatric Pompe Disease in the ADVANCE Participant Cohort. Journal of Neuromuscular Diseases, 9 (6), 713-730. https://doi.org/10.3233/JND-210784