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Enzyme replacement therapy outcomes across the disease spectrum: Findings from the mucopolysaccharidosis VI Clinical Surveillance Program.
J Inherit Metab Dis. 2019 05; 42(3):519-526.JI

Abstract

The impact of galsulfase enzyme replacement therapy in patients with mucopolysaccharidosis (MPS) VI with phenotypes at either end of the disease spectrum was evaluated. The MPS VI Clinical Surveillance Program (CSP) was established to collect long-term observational data from routine clinical and laboratory assessments. A subanalysis of the CSP was performed in patients with pretreatment urinary glycosaminoglycan (uGAG) levels <100 μg/mg and ≥200 μg/mg creatinine (low- and high-uGAG) who had received galsulfase for ≥6 months. uGAG, 6-minute walk test (6MWT), 3-minute stair climb test (3MSCT), pulmonary function measures, height/growth, cardiac function, and safety were evaluated. Patients with a high-uGAG level at pre-treatment baseline (N = 68) showed greater impairments in endurance and pulmonary function than those with low-baseline uGAG levels (N = 39). From pre-treatment baseline, the distance walked on the 6MWT in the low- and high-uGAG groups increased by a mean (±SD) of 49 (±151) meters and 42 (±165) meters (median follow-up 5.5 and 7.7 years), respectively. The number of stairs/min climbed in the 3MSCT in the low- and high-uGAG groups increased by a mean of 18 (±33) and 30 (±45) (median follow-up 2.8 and 3.5 years), respectively. Overall, pulmonary function remained unchanged for both groups. No impact was seen on cardiac function. Galsulfase was generally well tolerated in both groups, with most adverse events being MPS-related complications unrelated to galsulfase. Results of this CSP sub-analysis suggest that galsulfase stabilizes MPS VI in the long-term and has an acceptable safety profile, regardless of baseline disease severity.

Authors+Show Affiliations

Department of Gastroenterology, UCSF Benioff Children's Hospital Oakland, Oakland, California, USA.Department of Child Neurology, Justus-Liebig University, Gieβen, Germany.Department of Paediatrics, Fondazione MBBM San Gerardo Hospital, Monza, Italy. San Raffaele Telethon Institute for Gene Therapy (SR-TIGET), IRCCS San Raffaele Scientific Institute, Milan, Italy.Department of Endocrinology and Metabolic Medicine, Salford Royal Hospital NHS Foundation Trust, Salford, UK.Department of Metabolic Diseases, São João Hospital, Porto, Portugal.BioMarin Pharmaceutical Inc., Novato, California, USA.BioMarin Pharmaceutical Inc., Novato, California, USA.BioMarin Pharmaceutical Inc., Novato, California, USA.

Pub Type(s)

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

Language

eng

PubMed ID

30834539

Citation

Harmatz, Paul R., et al. "Enzyme Replacement Therapy Outcomes Across the Disease Spectrum: Findings From the Mucopolysaccharidosis VI Clinical Surveillance Program." Journal of Inherited Metabolic Disease, vol. 42, no. 3, 2019, pp. 519-526.
Harmatz PR, Lampe C, Parini R, et al. Enzyme replacement therapy outcomes across the disease spectrum: Findings from the mucopolysaccharidosis VI Clinical Surveillance Program. J Inherit Metab Dis. 2019;42(3):519-526.
Harmatz, P. R., Lampe, C., Parini, R., Sharma, R., Teles, E. L., Johnson, J., Sivam, D., & Sisic, Z. (2019). Enzyme replacement therapy outcomes across the disease spectrum: Findings from the mucopolysaccharidosis VI Clinical Surveillance Program. Journal of Inherited Metabolic Disease, 42(3), 519-526. https://doi.org/10.1002/jimd.12079
Harmatz PR, et al. Enzyme Replacement Therapy Outcomes Across the Disease Spectrum: Findings From the Mucopolysaccharidosis VI Clinical Surveillance Program. J Inherit Metab Dis. 2019;42(3):519-526. PubMed PMID: 30834539.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Enzyme replacement therapy outcomes across the disease spectrum: Findings from the mucopolysaccharidosis VI Clinical Surveillance Program. AU - Harmatz,Paul R, AU - Lampe,Christina, AU - Parini,Rossella, AU - Sharma,Reena, AU - Teles,Elisa L, AU - Johnson,Julie, AU - Sivam,Debbie, AU - Sisic,Zlatko, Y1 - 2019/04/08/ PY - 2018/10/15/received PY - 2019/02/27/accepted PY - 2019/3/6/pubmed PY - 2020/6/26/medline PY - 2019/3/6/entrez KW - Maroteaux-Lamy syndrome KW - disease severity, urinary GAG KW - efficacy KW - enzyme replacement therapy KW - galsulfase KW - mucopolysaccharidosis VI KW - registry, safety SP - 519 EP - 526 JF - Journal of inherited metabolic disease JO - J. Inherit. Metab. Dis. VL - 42 IS - 3 N2 - The impact of galsulfase enzyme replacement therapy in patients with mucopolysaccharidosis (MPS) VI with phenotypes at either end of the disease spectrum was evaluated. The MPS VI Clinical Surveillance Program (CSP) was established to collect long-term observational data from routine clinical and laboratory assessments. A subanalysis of the CSP was performed in patients with pretreatment urinary glycosaminoglycan (uGAG) levels <100 μg/mg and ≥200 μg/mg creatinine (low- and high-uGAG) who had received galsulfase for ≥6 months. uGAG, 6-minute walk test (6MWT), 3-minute stair climb test (3MSCT), pulmonary function measures, height/growth, cardiac function, and safety were evaluated. Patients with a high-uGAG level at pre-treatment baseline (N = 68) showed greater impairments in endurance and pulmonary function than those with low-baseline uGAG levels (N = 39). From pre-treatment baseline, the distance walked on the 6MWT in the low- and high-uGAG groups increased by a mean (±SD) of 49 (±151) meters and 42 (±165) meters (median follow-up 5.5 and 7.7 years), respectively. The number of stairs/min climbed in the 3MSCT in the low- and high-uGAG groups increased by a mean of 18 (±33) and 30 (±45) (median follow-up 2.8 and 3.5 years), respectively. Overall, pulmonary function remained unchanged for both groups. No impact was seen on cardiac function. Galsulfase was generally well tolerated in both groups, with most adverse events being MPS-related complications unrelated to galsulfase. Results of this CSP sub-analysis suggest that galsulfase stabilizes MPS VI in the long-term and has an acceptable safety profile, regardless of baseline disease severity. SN - 1573-2665 UR - https://www.unboundmedicine.com/medline/citation/30834539/Enzyme_replacement_therapy_outcomes_across_the_disease_spectrum:_Findings_from_the_mucopolysaccharidosis_VI_Clinical_Surveillance_Program_ L2 - https://doi.org/10.1002/jimd.12079 DB - PRIME DP - Unbound Medicine ER -