Hani Kushlaf, Jordi Díaz-Manera, Drago Bratkovic, Barry J Byrne, Kristl G Claeys, Paula R Clemens, Mazen M Dimachkie, Priya S Kishnani, Pascal Laforêt, Mark Roberts, Benedikt Schoser, Antonio Toscano, Jeff Castelli, Fred Holdbrook, Sheela Sitaraman Das, Mitchell Goldman, Tahseen Mozaffar
{"title":"转换酶替代疗法治疗迟发性庞贝病，从α糖苷酶到α糖苷酶加米卢司他：事后效应大小分析","authors":"Hani Kushlaf, Jordi Díaz-Manera, Drago Bratkovic, Barry J Byrne, Kristl G Claeys, Paula R Clemens, Mazen M Dimachkie, Priya S Kishnani, Pascal Laforêt, Mark Roberts, Benedikt Schoser, Antonio Toscano, Jeff Castelli, Fred Holdbrook, Sheela Sitaraman Das, Mitchell Goldman, Tahseen Mozaffar","doi":"10.1002/mus.28420","DOIUrl":null,"url":null,"abstract":"<p><strong>Introduction/aims: </strong>The randomized, double-blind PROPEL study (NCT03729362) suggested benefits for cipaglucosidase alfa plus miglustat (cipa+mig) versus alglucosidase alfa plus placebo (alg+pbo) in enzyme replacement therapy (ERT)-experienced adults with late-onset Pompe disease (LOPD). To further assess treatment response and the effect of switching treatment from alg to cipa+mig, we conducted a within-group effect size analysis in ERT-experienced patients.</p><p><strong>Methods: </strong>In this post hoc analysis, standardized within-group effect sizes (Cohen's d for correlated measurements from baseline to week 52) were calculated by dividing the mean change from baseline by the corresponding standard deviation for motor function, lung function, and muscle strength outcomes; patient-reported outcomes/quality of life; and biomarker levels (creatine kinase and hexose tetrasaccharide).</p><p><strong>Results: </strong>In PROPEL, 77% of patients received ERT with alg before study entry (median ERT duration 7.4 years). ERT-experienced patients remaining on alg+pbo (n = 30) generally showed within-group worsening (d ≤ -0.2) or stability (-0.2 < d < 0.2) across most outcomes, while those switched to cipa+mig (n = 65) mostly showed improvement (d ≥ 0.2) or stability. Patients remaining on alg+pbo demonstrated statistically significant worsening for several lung function outcomes, biomarker levels, and significant improvement for Patient-Reported Outcomes Measurement Information System (PROMIS)-Dyspnea. Patients switched to cipa+mig did not demonstrate significant worsening for any outcomes and showed significant improvements for 6-min walk distance (absolute and % predicted); upper, lower, and overall manual muscle testing; PROMIS-Fatigue; Physician (overall score) and Subject Global Impression of Change (5/8 subdomains); and biomarker levels.</p><p><strong>Discussion: </strong>ERT-experienced patients with LOPD who switched from alg to cipa+mig treatment achieved improvements or stability in most outcomes.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov identifier: NCT03729362.</p>","PeriodicalId":18968,"journal":{"name":"Muscle & Nerve","volume":" ","pages":"230-239"},"PeriodicalIF":3.1000,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Switching Enzyme Replacement Therapy for Late-Onset Pompe Disease From Alglucosidase Alfa to Cipaglucosidase Alfa Plus Miglustat: Post Hoc Effect Size Analysis of PROPEL.\",\"authors\":\"Hani Kushlaf, Jordi Díaz-Manera, Drago Bratkovic, Barry J Byrne, Kristl G Claeys, Paula R Clemens, Mazen M Dimachkie, Priya S Kishnani, Pascal Laforêt, Mark Roberts, Benedikt Schoser, Antonio Toscano, Jeff Castelli, Fred Holdbrook, Sheela Sitaraman Das, Mitchell Goldman, Tahseen Mozaffar\",\"doi\":\"10.1002/mus.28420\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Introduction/aims: </strong>The randomized, double-blind PROPEL study (NCT03729362) suggested benefits for cipaglucosidase alfa plus miglustat (cipa+mig) versus alglucosidase alfa plus placebo (alg+pbo) in enzyme replacement therapy (ERT)-experienced adults with late-onset Pompe disease (LOPD). To further assess treatment response and the effect of switching treatment from alg to cipa+mig, we conducted a within-group effect size analysis in ERT-experienced patients.</p><p><strong>Methods: </strong>In this post hoc analysis, standardized within-group effect sizes (Cohen's d for correlated measurements from baseline to week 52) were calculated by dividing the mean change from baseline by the corresponding standard deviation for motor function, lung function, and muscle strength outcomes; patient-reported outcomes/quality of life; and biomarker levels (creatine kinase and hexose tetrasaccharide).</p><p><strong>Results: </strong>In PROPEL, 77% of patients received ERT with alg before study entry (median ERT duration 7.4 years). ERT-experienced patients remaining on alg+pbo (n = 30) generally showed within-group worsening (d ≤ -0.2) or stability (-0.2 < d < 0.2) across most outcomes, while those switched to cipa+mig (n = 65) mostly showed improvement (d ≥ 0.2) or stability. Patients remaining on alg+pbo demonstrated statistically significant worsening for several lung function outcomes, biomarker levels, and significant improvement for Patient-Reported Outcomes Measurement Information System (PROMIS)-Dyspnea. Patients switched to cipa+mig did not demonstrate significant worsening for any outcomes and showed significant improvements for 6-min walk distance (absolute and % predicted); upper, lower, and overall manual muscle testing; PROMIS-Fatigue; Physician (overall score) and Subject Global Impression of Change (5/8 subdomains); and biomarker levels.</p><p><strong>Discussion: </strong>ERT-experienced patients with LOPD who switched from alg to cipa+mig treatment achieved improvements or stability in most outcomes.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov identifier: NCT03729362.</p>\",\"PeriodicalId\":18968,\"journal\":{\"name\":\"Muscle & Nerve\",\"volume\":\" \",\"pages\":\"230-239\"},\"PeriodicalIF\":3.1000,\"publicationDate\":\"2025-08-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Muscle & Nerve\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1002/mus.28420\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/5/7 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q2\",\"JCRName\":\"CLINICAL NEUROLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Muscle & Nerve","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1002/mus.28420","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/5/7 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
Switching Enzyme Replacement Therapy for Late-Onset Pompe Disease From Alglucosidase Alfa to Cipaglucosidase Alfa Plus Miglustat: Post Hoc Effect Size Analysis of PROPEL.
Introduction/aims: The randomized, double-blind PROPEL study (NCT03729362) suggested benefits for cipaglucosidase alfa plus miglustat (cipa+mig) versus alglucosidase alfa plus placebo (alg+pbo) in enzyme replacement therapy (ERT)-experienced adults with late-onset Pompe disease (LOPD). To further assess treatment response and the effect of switching treatment from alg to cipa+mig, we conducted a within-group effect size analysis in ERT-experienced patients.
Methods: In this post hoc analysis, standardized within-group effect sizes (Cohen's d for correlated measurements from baseline to week 52) were calculated by dividing the mean change from baseline by the corresponding standard deviation for motor function, lung function, and muscle strength outcomes; patient-reported outcomes/quality of life; and biomarker levels (creatine kinase and hexose tetrasaccharide).
Results: In PROPEL, 77% of patients received ERT with alg before study entry (median ERT duration 7.4 years). ERT-experienced patients remaining on alg+pbo (n = 30) generally showed within-group worsening (d ≤ -0.2) or stability (-0.2 < d < 0.2) across most outcomes, while those switched to cipa+mig (n = 65) mostly showed improvement (d ≥ 0.2) or stability. Patients remaining on alg+pbo demonstrated statistically significant worsening for several lung function outcomes, biomarker levels, and significant improvement for Patient-Reported Outcomes Measurement Information System (PROMIS)-Dyspnea. Patients switched to cipa+mig did not demonstrate significant worsening for any outcomes and showed significant improvements for 6-min walk distance (absolute and % predicted); upper, lower, and overall manual muscle testing; PROMIS-Fatigue; Physician (overall score) and Subject Global Impression of Change (5/8 subdomains); and biomarker levels.
Discussion: ERT-experienced patients with LOPD who switched from alg to cipa+mig treatment achieved improvements or stability in most outcomes.
期刊介绍：
Muscle & Nerve is an international and interdisciplinary publication of original contributions, in both health and disease, concerning studies of the muscle, the neuromuscular junction, the peripheral motor, sensory and autonomic neurons, and the central nervous system where the behavior of the peripheral nervous system is clarified. Appearing monthly, Muscle & Nerve publishes clinical studies and clinically relevant research reports in the fields of anatomy, biochemistry, cell biology, electrophysiology and electrodiagnosis, epidemiology, genetics, immunology, pathology, pharmacology, physiology, toxicology, and virology. The Journal welcomes articles and reports on basic clinical electrophysiology and electrodiagnosis. We expedite some papers dealing with timely topics to keep up with the fast-moving pace of science, based on the referees'' recommendation.
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