Higher Dose Alglucosidase Alfa Is Associated With Improved Overall Survival In Infantile-Onset Pompe Disease (IOPD): Data From the Pompe Registry

Authors

Priya S. Kishnani, Division of Medical Genetics, Department of Pediatrics, Duke University Medical Center, Durham, NC, USA. priya.kishnani@duke.edu.
David Kronn, Department of Pathology and Pediatrics, New York Medical College, Valhalla, NY, USA.Follow
Shugo Suwazono, Center for Clinical Neuroscience, National Hospital Organization Okinawa National Hospital, Ginowan, Japan.
Alexander Broomfield, Willink Biochemical Genetics Unit, Manchester Center for Genomic Medicine, St Mary's Hospital, Central Manchester Foundation Trust, Manchester, UK.
Juan Llerena, Centro de Genética Médica, Instituto Fernandes Figueira/FIOCRUZ, Rio de Janeiro, Brazil.
Zuhair Nasser Al-Hassnan, Department of Medical Genomics, Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
Julie L. Batista, Sanofi, Cambridge, MA, USA.
Kathryn M. Wilson, Navitas Data Sciences, Pottstown, PA, USA.
Magali Periquet, Sanofi, Berlin, Germany.
Nadia Daba, Sanofi, Dubai, United Arab Emirates.
Andreas Hahn, Department of Child Neurology, University Hospital Giessen, Giessen, Germany.
Yin-Hsiu Chien, Department of Medical Genetics and Pediatrics, National Taiwan University Hospital, Taipei, Taiwan.

Author Type(s)

Faculty

DOI

https://doi.org/10.1186/s13023-023-02981-2

Journal Title

Orphanet Journal of Rare Diseases

First Page

381

Document Type

Article

Publication Date

12-6-2023

Department

Pediatrics

Abstract

BACKGROUND: Studies indicate that doses of alglucosidase alfa (ALGLU) higher than label dose (20 mg/kg every other week) improve clinical outcomes in infantile-onset Pompe disease (IOPD). We investigated data from the Pompe Registry to determine the association between ALGLU dose and survival in IOPD. RESULTS: We included 332 IOPD patients from the Registry as of January 2022 who had cardiomyopathy and were first treated at age < 1 year. We used Cox proportional hazards models to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the association between ALGLU as a time-varying exposure and survival, adjusting for age at first treatment, sex, and cross-reactive immunologic material (CRIM)/immune tolerance induction (ITI) status. Dose was measured as average relative dose received over time (in multiples of label dose, range > 0 to 4 times label dose), current dose, and lagged dose. 81% patients received label dose at treatment initiation. Over time, 52% received a higher dose. Higher ALGLU dose over time was associated with improved survival: adjusted HR 0.40 (95% CI 0.22-0.73, p = 0.003) per 1-unit increase in average relative dose, with similar results for invasive ventilation-free survival (adjusted HR 0.48, 95% CI 0.28-0.84; p = 0.010). The association was consistent in patients first treated before or after 3 months of age and did not vary significantly by CRIM status. Results for current and lagged dose were similar to average dose. CONCLUSIONS: Higher ALGLU doses were associated with significantly improved overall and invasive ventilator-free survival in IOPD. Results were consistent across sensitivity analyses.

Recommended Citation

Kishnani, P. S., Kronn, D., Suwazono, S., Broomfield, A., Llerena, J., Al-Hassnan, Z. N., Batista, J. L., Wilson, K. M., Periquet, M., Daba, N., Hahn, A., & Chien, Y. (2023). Higher Dose Alglucosidase Alfa Is Associated With Improved Overall Survival In Infantile-Onset Pompe Disease (IOPD): Data From the Pompe Registry. Orphanet Journal of Rare Diseases, 18 (1), 381. https://doi.org/https://doi.org/10.1186/s13023-023-02981-2