Motor Responses in Pediatric Pompe Disease in the ADVANCE Participant Cohort

Author:

Duong Tina1ORCID,Kishnani Priya S.2,An Haack Kristina3,Foster Meredith C.4,Gibson James B.5,Wilson Catherine4,Hahn Si Houn6,Hillman Richard7,Kronn David8,Leslie Nancy D.9,Peña Loren D.M.21011,Sparks Susan E.4,Stockton David W.12,Tanpaiboon Pranoot1314,Day John W.1,

Affiliation:

1. Department of Neurology, Division of Neuromuscular Medicine, Stanford University School of Medicine, Palo Alto, CA, USA

2. Department of Pediatrics, Duke University Medical Center, Durham, NC, USA

3. Sanofi, Chilly-Mazarin, France

4. Sanofi, Cambridge, MA, USA

5. Clinical and Metabolic Genetics, Dell Children’s Medical Group, Austin, TX, USA

6. Departments of Pediatrics and Medicine and Biochemical Genetics Program, Seattle Children’s Hospital/University of Washington, Seattle, WA, USA

7. University of Missouri Child Health, Columbia, MO, USA

8. Departments of Pathology and Pediatrics, New York Medical College, Valhalla, NY, USA

9. Division of Human Genetics, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA

10. Current address: Division of Human Genetics, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA

11. Current address: University of Cincinnati College of Medicine, Cincinnati, OH, USA

12. Division of Genetic, Genomic, and Metabolic Disorders, Central Michigan University and Children’s Hospital of Michigan, Detroit, MI, USA

13. Rare Disease Institute, Children’s National Hospital, Washington, DC, USA

14. Current address: Division of Medical Genetics, Child Health Research Center, Torrance, CA, USA

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

Publisher

IOS Press

Subject

Neurology (clinical),Neurology

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