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Safety and efficacy of alternative alglucosidase alfa regimens in Pompe disease.
Neuromuscul Disord 2015; 25(4):321-32ND

Abstract

Emerging phenotypes in long-term survivors with Pompe disease on standard enzyme replacement therapy (ERT) (alglucosidase alfa 20 mg/kg/2 weeks) can include patients with worsening motor function. Whether higher doses of ERT improve skeletal function in these patients has not been systematically studied. This exploratory, randomized, open-label, 52-week study examined the safety and efficacy of 2 ERT regimens of alglucosidase alfa (20 mg/kg/week or 40 mg/kg/2 weeks) in 13 patients with Pompe disease and clinical decline or a lack of improvement on standard ERT: late-onset (n = 4), infantile-onset (n = 9). Cross-reactive immunologic material assay-negative patients were excluded. Eleven of 13 patients completed the study. Trends for improvement were seen in total gross motor function, but not mobility; however, 6 (late-onset, 2; infantile-onset, 4) of 11 patients (55%) who met the entry criteria of motor decline (late-onset, 4; infantile-onset, 7) showed improvement in motor and/or mobility skills. No between-regimen differences in efficacy emerged. Two case studies highlight the benefits of increased ERT dose in patients with Pompe disease experiencing clinical decline. Both alternative regimens were generally well tolerated. This study was limited by the small sample size, which is not uncommon for small clinical studies of rare diseases. Additionally, the study did not include direct assessment of muscle pathology, which may have identified potential causes of decreased response to ERT. Results were inconclusive but suggest that increased ERT dose may be beneficial in some patients with Pompe disease experiencing motor decline. Controlled studies are needed to clarify the benefits and risks of this strategy.

Authors+Show Affiliations

Duke University Medical Center, Durham, North Carolina, USA.Genzyme, a sanofi company, Cambridge, Massachusetts, USA.Genzyme, a sanofi company, Cambridge, Massachusetts, USA.Alberta Children's Hospital, Alberta, Canada.Ann and Robert H. Lurie Children's Hospital of Chicago, IL, USA.Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.University of Kansas Medical Center, Kansas City, Kansas, USA.Duke University Medical Center, Durham, North Carolina, USA.Infusion Associates, Grand Rapids, Michigan, USA.Adirondack Pediatrics, Glens Falls, New York, USA.The Royal Children's Hospital, Victoria, Australia.Genzyme, a sanofi company, Cambridge, Massachusetts, USA.Parker Hill Oncology & Hematology, PC, Roxbury Crossing, Massachusetts, USA.Children's National Medical Center, District of Columbia, USA.Duke University Medical Center, Durham, North Carolina, USA. Electronic address: priya.kishnani@duke.edu.

Pub Type(s)

Clinical Trial
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25617983

Citation

Case, Laura E., et al. "Safety and Efficacy of Alternative Alglucosidase Alfa Regimens in Pompe Disease." Neuromuscular Disorders : NMD, vol. 25, no. 4, 2015, pp. 321-32.
Case LE, Bjartmar C, Morgan C, et al. Safety and efficacy of alternative alglucosidase alfa regimens in Pompe disease. Neuromuscul Disord. 2015;25(4):321-32.
Case, L. E., Bjartmar, C., Morgan, C., Casey, R., Charrow, J., Clancy, J. P., ... Kishnani, P. S. (2015). Safety and efficacy of alternative alglucosidase alfa regimens in Pompe disease. Neuromuscular Disorders : NMD, 25(4), pp. 321-32. doi:10.1016/j.nmd.2014.12.004.
Case LE, et al. Safety and Efficacy of Alternative Alglucosidase Alfa Regimens in Pompe Disease. Neuromuscul Disord. 2015;25(4):321-32. PubMed PMID: 25617983.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Safety and efficacy of alternative alglucosidase alfa regimens in Pompe disease. AU - Case,Laura E, AU - Bjartmar,Carl, AU - Morgan,Claire, AU - Casey,Robin, AU - Charrow,Joel, AU - Clancy,John P, AU - Dasouki,Majed, AU - DeArmey,Stephanie, AU - Nedd,Khan, AU - Nevins,Mary, AU - Peters,Heidi, AU - Phillips,Dawn, AU - Spigelman,Zachary, AU - Tifft,Cynthia, AU - Kishnani,Priya S, Y1 - 2014/12/19/ PY - 2014/07/16/received PY - 2014/11/21/revised PY - 2014/12/16/accepted PY - 2015/1/26/entrez PY - 2015/1/27/pubmed PY - 2015/12/15/medline KW - Alglucosidase alfa KW - Clinical decline KW - Dose KW - Enzyme replacement therapy KW - Infantile onset KW - Late onset KW - Pompe disease SP - 321 EP - 32 JF - Neuromuscular disorders : NMD JO - Neuromuscul. Disord. VL - 25 IS - 4 N2 - Emerging phenotypes in long-term survivors with Pompe disease on standard enzyme replacement therapy (ERT) (alglucosidase alfa 20 mg/kg/2 weeks) can include patients with worsening motor function. Whether higher doses of ERT improve skeletal function in these patients has not been systematically studied. This exploratory, randomized, open-label, 52-week study examined the safety and efficacy of 2 ERT regimens of alglucosidase alfa (20 mg/kg/week or 40 mg/kg/2 weeks) in 13 patients with Pompe disease and clinical decline or a lack of improvement on standard ERT: late-onset (n = 4), infantile-onset (n = 9). Cross-reactive immunologic material assay-negative patients were excluded. Eleven of 13 patients completed the study. Trends for improvement were seen in total gross motor function, but not mobility; however, 6 (late-onset, 2; infantile-onset, 4) of 11 patients (55%) who met the entry criteria of motor decline (late-onset, 4; infantile-onset, 7) showed improvement in motor and/or mobility skills. No between-regimen differences in efficacy emerged. Two case studies highlight the benefits of increased ERT dose in patients with Pompe disease experiencing clinical decline. Both alternative regimens were generally well tolerated. This study was limited by the small sample size, which is not uncommon for small clinical studies of rare diseases. Additionally, the study did not include direct assessment of muscle pathology, which may have identified potential causes of decreased response to ERT. Results were inconclusive but suggest that increased ERT dose may be beneficial in some patients with Pompe disease experiencing motor decline. Controlled studies are needed to clarify the benefits and risks of this strategy. SN - 1873-2364 UR - https://www.unboundmedicine.com/medline/citation/25617983/Safety_and_efficacy_of_alternative_alglucosidase_alfa_regimens_in_Pompe_disease_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0960-8966(14)00724-X DB - PRIME DP - Unbound Medicine ER -