Top

Published in:

Open Access 01-12-2017 | Research

Clinical outcomes in a subpopulation of adults with Morquio A syndrome: results from a long-term extension study of elosulfase alfa

Authors: D. Hughes, R. Giugliani, N. Guffon, S. A. Jones, K. E. Mengel, R. Parini, R. Matousek, S. M. Hawley, A. Quartel

Published in: Orphanet Journal of Rare Diseases | Issue 1/2017

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.

Available only for authorised users

Yasuda E, Fushimi K, Suzuki Y, Shimizu K, Takami T, Zustin J, Patel P, Ruhnke K, Shimada T, Boyce B, Kokas T, Barone C, Theroux M, Mackenzie W, Nagel B, Ryerse JS, Orii KE, Iida H, Orii T, Tomatsu S. Pathogenesis of Morquio A syndrome: an autopsied case reveals systemic storage disorder. Mol Genet Metab. 2013;109:301–11.CrossRefPubMed

Hendriksz CJ, Berger KI, Giugliani R, Harmatz P, Kampmann C, Mackenzie WG, Raiman J, Villareal MS, Savarirayan R. International guidelines for the management and treatment of Morquio A syndrome. Am J Med Genet A. 2015;167A:11–25.CrossRefPubMed

Harmatz P, Mengel KE, Giugliani R, Valayannopoulos V, Lin SP, Parini R, Guffon N, Burton BK, Hendriksz CJ, Mitchell J, Martins A, Jones S, Guelbert N, Vellodi A, Hollak C, Slasor P, Decker C. The Morquio A clinical assessment program: baseline results illustrating progressive, multisystemic clinical impairments in Morquio A subjects. Mol Genet Metab. 2013;109:54–61.CrossRefPubMed

Tomatsu S, Montaño AM, Oikawa H, Smith M, Barrera L, Chinen Y, Thacker MM, Mackenzie WG, Suzuki Y, Orii T. Mucopolysaccharidosis type IVA (Morquio A disease): clinical review and current treatment. Curr Pharm Biotechnol. 2011;12:931–45.CrossRefPubMed

Leadley RM, Lang S, Misso K, Bekkering T, Ross J, Akiyama T, Fietz M, Giugliani R, Hendriksz CJ, Hock NL, McGill J, Olaye A, Jain M, Kleijnen J. A systematic review of the prevalence of Morquio A syndrome: challenges for study reporting in rare diseases. Orphanet J Rare Dis. 2014;9:173.CrossRefPubMedPubMedCentral

Harmatz PR, Mengel KE, Giugliani R, Valayannopoulos V, Lin SP, Parini R, Guffon N, Burton BK, Hendriksz CJ, Mitchell JJ, Martins AM, Jones SA, Guelbert N, Vellodi A, Wijburg FA, Yang K, Slasor P, Decker C. Longitudinal analysis of endurance and respiratory function from a natural history study of Morquio A syndrome. Mol Genet Metab. 2015;114:186–94.CrossRefPubMed

Hendriksz CJ, Lavery C, Coker M, Ucar SK, Jain M, Bell L, Lampe C. Burden of disease in patients with Morquio A syndrome: results from an international patient-reported outcomes survey. Orphanet J Rare Dis. 2014;9:32.CrossRefPubMedPubMedCentral

Lavery C, Hendriksz C. Mortality in patients with Morquio syndrome A. JIMD Rep. 2015;15:59–66.PubMed

Montaño AM, Tomatsu S, Gottesman GS, Smith M, International OT, Morquio A. Registry: clinical manifestation and natural course of Morquio A disease. J Inherit Metab Dis. 2007;30:165–74.CrossRefPubMed

10.

Sanford M, Lo JH. Elosulfase alfa: first global approval. Drugs. 2014;74:713–8.CrossRefPubMed

11.

Hendriksz CJ, Giugliani R, Harmatz P, Mengel E, Guffon N, Valayannopoulous V, Parini R, Hughes D, Pastores GM, Lau HA, Al-Sayed MD, Raiman J, Investigators STRIVE, Yang K, Mealiffe M, Haller C. Multi-domain impact of elosulfase alfa in Morquio A syndrome in the pivotal phase III trial. Mol Genet Metab. 2015;114:178–85.CrossRefPubMed

12.

Hendriksz CJ, Parini R, AlSayed MD, Raiman J, Giugliani R, Villarreal MLS, Mitchell JJ, Burton BK, Guelbert N, Stewart F, Hughes DA, Berger KI, Slasor P, Matousek R, Jurecki E, Shaywitz AJ, Harmatz PR. Long-term endurance and safety of elosulfase alfa enzyme replacement therapy in patients with Morquio A syndrome. Mol Genet Metab. 2016;119:131–43.CrossRefPubMed

13.

Hendriksz CJ, Burton B, Fleming TR, Harmatz P, Hughes D, Jones SA, Lin SP, Mengel E, Scarpa M, Valayannopoulos V, Giugliani R, STRIVE Investigators, Slasor P, Lounsbury D, Dummer W. Efficacy and safety of enzyme replacement therapy with BMN 110 (elosulfase alfa) for Morquio A syndrome (mucopolysaccharidosis IVA): a phase 3 randomised placebo-controlled study. J Inherit Metab Dis. 2014;37:979–90.CrossRefPubMedPubMedCentral

14.

Franco JF, Soares DC, Torres LC, Leal GN, Cunha MT, Honjo RS, Bertola DR, Kim CA. Impact of early enzyme-replacement therapy for mucopolysaccharidosis VI: results of a long-term follow-up of Brazilian siblings. Genet Mol Res. 2016;15(1):1–7.

15.

Leal GN, de Paula AC, Morhy SS, Andrade JL, Kim CA. Advantages of early replacement therapy for mucopolysaccharidosis type VI: echocardiographic follow-up of siblings. Cardiol Young. 2014;24:229–35.CrossRefPubMed

16.

Furujo M, Kubo T, Kosuga M, Okuyama T. Enzyme replacement therapy attenuates disease progression in two Japanese siblings with mucopolysaccharidosis type VI. Mol Genet Metab. 2011;104:597–602.CrossRefPubMed

17.

McGill JJ, Inwood AC, Coman DJ, Lipke ML, de Lore D, Swiedler SJ, Hopwood JJ. Enzyme replacement therapy for mucopolysaccharidosis VI from 8 weeks of age—a sibling control study. Clin Genet. 2010;77:492–8.CrossRefPubMed

18.

Gabrielli O, Clarke LA, Ficcadenti A, Santoro L, Zampini L, Volpi N, Coppa GV. 12 years follow up of enzyme-replacement therapy in two siblings with attenuated mucopolysaccharidosis I: the important role of early treatment. BMC Med Genet. 2016;17:19.CrossRefPubMedPubMedCentral

19.

Al-Sannaa NA, Bay L, Barbouth DS, Benhayoun Y, Goizet C, Guelbert N, Jones SA, Kyosen SO, Martins AM, Phornphutkul C, Reig C, Pleat R, Fallet S, Holder II. Early treatment with laronidase improves clinical outcomes in patients with attenuated MPS I: a retrospective case series analysis of nine sibships. Orphanet J Rare Dis. 2015;10:131.CrossRefPubMedPubMedCentral

20.

American Thoracic Society. Standardization of spirometry, 1994 update. Am J Respir Crit Care Med. 1995;152:1107–36.CrossRef

Title: Clinical outcomes in a subpopulation of adults with Morquio A syndrome: results from a long-term extension study of elosulfase alfa
Authors: D. Hughes
R. Giugliani
N. Guffon
S. A. Jones
K. E. Mengel
R. Parini
R. Matousek
S. M. Hawley
A. Quartel
Publication date: 01-12-2017
Publisher: BioMed Central
Published in: Orphanet Journal of Rare Diseases / Issue 1/2017
Electronic ISSN: 1750-1172
DOI: https://doi.org/10.1186/s13023-017-0634-0

At a glance: The STEP trials

Springer Medicine

Clinical outcomes in a subpopulation of adults with Morquio A syndrome: results from a long-term extension study of elosulfase alfa

Abstract

Background

Results

Conclusions

Trial registration

At a glance: The STEP trials

Springer Medicine

Abstract

Background

Results

Conclusions

Trial registration

Please log in to get access to this content

Other articles of this Issue 1/2017

Australian children living with rare diseases: experiences of diagnosis and perceived consequences of diagnostic delays

Early diagnosis and care is achieved but should be improved in infants with Prader-Willi syndrome

Impacts of caring for a child with the CDKL5 disorder on parental wellbeing and family quality of life

Erratum to: Quantification of gait in mitochondrial m.3243A > G patients: a validation study

Do investors value the FDA orphan drug designation?

Neurological outcome of patients with cryopyrin-associated periodic syndrome (CAPS)