Clinical outcomes in a subpopulation of adults with Morquio A syndrome: results from a long-term extension study of elosulfase alfa
Abstract Background This post hoc subanalysis examined outcomes in adult patients with Morquio A (mucopolysaccharidosis IVA) who received enzyme replacement therapy (ERT) with elosulfase alfa over a 120-weeks period. Patients ≥18 years of age evaluated in an open-label, long-term extension study of...
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doaj-4721627440df49499df6211cfe57b3d12020-11-24T21:49:04ZengBMCOrphanet Journal of Rare Diseases1750-11722017-05-011211810.1186/s13023-017-0634-0Clinical outcomes in a subpopulation of adults with Morquio A syndrome: results from a long-term extension study of elosulfase alfaD. Hughes0R. Giugliani1N. Guffon2S. A. Jones3K. E. Mengel4R. Parini5R. Matousek6S. M. Hawley7A. Quartel8Royal Free London NHS Foundation Trust and University College LondonMedical Genetics Service, Hospital de Clínicas de Porto Alegre and Department of Genetics/Universidade Federal do Rio Grande do Sul and Instituto Nacional de Genética Médica PopulacionalHôpital Femme Mère Enfant, Reference Centre of Inherited Metabolic Diseases, Hospices Civils de LyonManchester Centre for Genomic Medicine, St Mary’s Hospital, Central Manchester University Hospitals NHS Foundation Trust, University of ManchesterVilla Metabolica, Centre for Pediatric and Adolescent Medicine, University of Mainz Medical CenterFondazione Monza e Brianza per il Bambino e la sua Mamma, Azienda Ospedaliera San GerardoBioMarin Pharmaceutical IncBioMarin Pharmaceutical IncBioMarin Pharmaceutical IncAbstract Background This post hoc subanalysis examined outcomes in adult patients with Morquio A (mucopolysaccharidosis IVA) who received enzyme replacement therapy (ERT) with elosulfase alfa over a 120-weeks period. Patients ≥18 years of age evaluated in an open-label, long-term extension study of elosulfase alfa (modified per protocol [MPP], n = 32; intent-to-treat [ITT], n = 37; MOR-005; NCT01415427) were compared with the ≥18-year-old untreated population with 2-years follow-up from a Morquio A natural history study (n = 10; MorCAP; NCT00787995). The MOR-005 MPP population excluded patients who underwent orthopedic surgical procedures or were noncompliant with study protocol (defined as missing ≥20% of ERT infusions). No MorCAP patients underwent orthopedic surgical procedures during the relevant time period. Endurance was assessed by the 6-min walk test (6MWT) and 3-min stair climb test (3MSCT). Activities of daily living (ADLs) were assessed by the MPS Health Assessment Questionnaire (MPS HAQ). Results Least squares (LS) mean (SE) 6MWT distances increased by 34.9 (11.7) m (MPP) and 30.5 (10.8) m (ITT) by week 120; LS mean (SE) change in 3MSCT at week 120 was 6.7 (1.8) stairs/min (MPP) and 5.9 (1.7) stairs/min (ITT). MorCAP patients showed no improvement in 6MWT distance or 3MSCT over a similar period of time. Pulmonary function measures remained unchanged in both MOR-005 and MorCAP adults. All MPS HAQ domain scores improved in MOR-005 adults, whereas MorCAP adults had unchanged caregiver assistance and mobility outcomes and worsened self-care outcomes. Conclusions Long-term ERT in adult patients with Morquio A was associated with increased endurance and improvement in performance of ADLs. Trial registration Trial Registration NCT01415427 . Name of registry: Long-Term Efficacy and Safety Extension Study of BMN 110 in Patients With Mucopolysaccharidosis IVA (Morquio A Syndrome). Registered 8 August 2011, retrospectively registered.http://link.springer.com/article/10.1186/s13023-017-0634-0Morquio syndrome AAdultsAdulthoodAdvanced diseaseLong-termEnzyme replacement therapy |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
D. Hughes R. Giugliani N. Guffon S. A. Jones K. E. Mengel R. Parini R. Matousek S. M. Hawley A. Quartel |
spellingShingle |
D. Hughes R. Giugliani N. Guffon S. A. Jones K. E. Mengel R. Parini R. Matousek S. M. Hawley A. Quartel Clinical outcomes in a subpopulation of adults with Morquio A syndrome: results from a long-term extension study of elosulfase alfa Orphanet Journal of Rare Diseases Morquio syndrome A Adults Adulthood Advanced disease Long-term Enzyme replacement therapy |
author_facet |
D. Hughes R. Giugliani N. Guffon S. A. Jones K. E. Mengel R. Parini R. Matousek S. M. Hawley A. Quartel |
author_sort |
D. Hughes |
title |
Clinical outcomes in a subpopulation of adults with Morquio A syndrome: results from a long-term extension study of elosulfase alfa |
title_short |
Clinical outcomes in a subpopulation of adults with Morquio A syndrome: results from a long-term extension study of elosulfase alfa |
title_full |
Clinical outcomes in a subpopulation of adults with Morquio A syndrome: results from a long-term extension study of elosulfase alfa |
title_fullStr |
Clinical outcomes in a subpopulation of adults with Morquio A syndrome: results from a long-term extension study of elosulfase alfa |
title_full_unstemmed |
Clinical outcomes in a subpopulation of adults with Morquio A syndrome: results from a long-term extension study of elosulfase alfa |
title_sort |
clinical outcomes in a subpopulation of adults with morquio a syndrome: results from a long-term extension study of elosulfase alfa |
publisher |
BMC |
series |
Orphanet Journal of Rare Diseases |
issn |
1750-1172 |
publishDate |
2017-05-01 |
description |
Abstract Background This post hoc subanalysis examined outcomes in adult patients with Morquio A (mucopolysaccharidosis IVA) who received enzyme replacement therapy (ERT) with elosulfase alfa over a 120-weeks period. Patients ≥18 years of age evaluated in an open-label, long-term extension study of elosulfase alfa (modified per protocol [MPP], n = 32; intent-to-treat [ITT], n = 37; MOR-005; NCT01415427) were compared with the ≥18-year-old untreated population with 2-years follow-up from a Morquio A natural history study (n = 10; MorCAP; NCT00787995). The MOR-005 MPP population excluded patients who underwent orthopedic surgical procedures or were noncompliant with study protocol (defined as missing ≥20% of ERT infusions). No MorCAP patients underwent orthopedic surgical procedures during the relevant time period. Endurance was assessed by the 6-min walk test (6MWT) and 3-min stair climb test (3MSCT). Activities of daily living (ADLs) were assessed by the MPS Health Assessment Questionnaire (MPS HAQ). Results Least squares (LS) mean (SE) 6MWT distances increased by 34.9 (11.7) m (MPP) and 30.5 (10.8) m (ITT) by week 120; LS mean (SE) change in 3MSCT at week 120 was 6.7 (1.8) stairs/min (MPP) and 5.9 (1.7) stairs/min (ITT). MorCAP patients showed no improvement in 6MWT distance or 3MSCT over a similar period of time. Pulmonary function measures remained unchanged in both MOR-005 and MorCAP adults. All MPS HAQ domain scores improved in MOR-005 adults, whereas MorCAP adults had unchanged caregiver assistance and mobility outcomes and worsened self-care outcomes. Conclusions Long-term ERT in adult patients with Morquio A was associated with increased endurance and improvement in performance of ADLs. Trial registration Trial Registration NCT01415427 . Name of registry: Long-Term Efficacy and Safety Extension Study of BMN 110 in Patients With Mucopolysaccharidosis IVA (Morquio A Syndrome). Registered 8 August 2011, retrospectively registered. |
topic |
Morquio syndrome A Adults Adulthood Advanced disease Long-term Enzyme replacement therapy |
url |
http://link.springer.com/article/10.1186/s13023-017-0634-0 |
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