Introduction: Mucopolysaccharidosis (MPS) IVA or Morquio A syndrome is an autosomal recessive lysosomal storage disorder (LSD) caused by deficiency of the N-acetylgalactosamine-6-sulfatase (GALNS) enzyme, which impairs lysosomal degradation of keratan sulphate and chondroitin-6-sulphate. The multiple clinical manifestations of MPS IVA present numerous challenges for management and necessitate the need for individualised treatment. Although treatment guidelines are available, the methodology used to develop this guidance has come under increased scrutiny. This programme was conducted to provide evidence-based, expert-agreed recommendations to optimise management of MPS IVA. Methods: Twenty six international healthcare professionals across multiple disciplines, with expertise in managing MPS IVA, and three patient advocates formed the Steering Committee (SC) and contributed to the development of this guidance. Representatives from six Patient Advocacy Groups (PAGs) were interviewed to gain insights on patient perspectives. A modified-Delphi methodology was used to demonstrate consensus among a wider group of healthcare professionals with experience managing patients with MPS IVA and the manuscript was evaluated against the validated Appraisal of Guidelines for Research and Evaluation (AGREE II) instrument by three independent reviewers. Results: A total of 87 guidance statements were developed covering five domains: (1) general management principles; (2) recommended routine monitoring and assessments; (3) disease-modifying interventions (enzyme replacement therapy [ERT] and haematopoietic stem cell transplantation [HSCT]); (4) interventions to support respiratory and sleep disorders; (5) anaesthetics and surgical interventions (including spinal, limb, ophthalmic, cardio-thoracic and ear-nose-throat [ENT] surgeries). Consensus was reached on all statements after two rounds of voting. The overall guideline AGREE II assessment score obtained for the development of the guidance was 5.3/7 (where 1 represents the lowest quality and 7 represents the highest quality of guidance). Conclusion: This manuscript provides evidence- A nd consensus-based recommendations for the management of patients with MPS IVA and is for use by healthcare professionals that manage the holistic care of patients with the intention to improve clinical- A nd patient-reported outcomes and enhance patient quality of life. It is recognised that the guidance provided represents a point in time and further research is required to address current knowledge and evidence gaps.
Bibliographical noteFunding Information:
The authors would like to remember and dedicate this paper to their colleague and fellow SC member, Christine Lavery, MBE, Chief Executive of the Society for Mucopolysaccharide Diseases (MPS Society) and fearless advocate for those with MPS, who sadly passed away before completion of this programme. The authors would like to thank Dr. Francyne Kubaski, BS, MSc, PhD, of HCPA and UFRGS, Porto Alegre, Brazil and Dr. Gregory Lamb and Dr. Kealeboga Rammego, of Steve Biko Academic Unit, University of Pretoria, South Africa for their role as Bibliographic Fellows and assistance with literature searches and analysis; Michele Hilton Boon, Angela Perez Gomez and Karen Spithoff for reviewing the manuscript against the AGREE II Instrument; The PAG groups: Casa Hunter, German MPS Society, National MPS Society, The Isaac Foundation, Turkish MPS Society and UK MPS Society for their consultations which informed the guidance development. Programme support was provided by Rebecca Bellerby PhD, Hannah Tivey PhD and James Hadfield, BA (Oxon) of Lucid Partners Ltd., Burleighfield House, Buckinghamshire, United Kingdom. Medical writing and editorial support to the authors in the development of this manuscript was provided by Lucid Partners Ltd., Burleighfield House, Buckinghamshire, United Kingdom; financial support for these services was provided by BioMarin. MPS Consensus Programme Steering Committee: Mehmet Umut Akyol, Tord D. Alden, Hernan Amartino, Jane Ashworth, Kumar Belani, Kenneth I. Berger, Andrea Borgo, Elizabeth Braunlin, Yoshikatsu Eto, Jeffrey I. Gold, Andrea Jester, Simon A. Jones, Cengiz Karsli, William Mackenzie, Diane Ruschel Marinho, Andrew McFadyen, Jim McGill, John J. Mitchell, Joseph Muenzer, Torayuki Okuyama, Paul J. Orchard, Bob Stevens, Sophie Thomas, Robert Walker, Robert Wynn. MPS Consensus Programme Co-Chairs: Roberto Giugliani, Paul Harmatz, Christian Hendriksz, Maurizio Scarpa.
The programme was funded by BioMarin. BioMarin were not involved in any stages of the process and did not influence the design or content of the programme. BioMarin were absent from all SC meetings, were blinded to the guidance statements and were not involved in the publication process. The programme was managed by an independent secretariat (Lucid Partners Ltd), and the scope of the programme and content, including the development of guidance statements, was led by the SC with editorial support provided by the secretariat. The SC was identified through a systematic expert mapping process, conducted independently of the funder.
C Hendriksz; is Owner and Director of FYMCA Medical Ltd.; has conducted consultancy work for Actelion, Amicus, Alexion, Audentes, BioMarin Pharmaceutical Inc., Chiesi, Evidera, Inventiva, GSK, SOBI, Health Care at Home, Sanofi Genzyme, Shire. P Harmatz has conducted consultancy work and/or has received grant support from Alexion, Armagen, BioMarin Pharmaceutical Inc., Chiesi, Denali, Genzyme, Enzyvant, Inventiva, JCR Pharmaceuticals, Orphazyme, Pfizer, PTC Therapeutics, RegenXbio, Sangamo, Shire, SOBI and Ultragenyx. R Giugliani has received consultancy fees, and/or investigator fees, and/or speaker honoraria and/or travel grants to attend scientific meetings from Actelion, Amicus, Armagen, BioMarin, Chiesi, GC Pharma, Inventiva, JCR Pharmaceuticals, Lysogene, RegenxBio, Sanofi Genzyme, Shire, Sobi, and Ultragenyx. M Scarpa has received honoraria, research and travel grants from Alexion, BioMarin Pharmaceutical Inc., Chiesi, Sanofi Genzyme, Shire, Ultragenix and Sangamo. MU Akyol has received speaker honoraria and travel grants from Shire. J Ashworth has received honoraria, travel expenses and a research grant from BioMarin Pharmaceutical Inc. and has received consultancy fees from AbbVie and Inventiva. T Alden has received consultant and honoraria payments from BioMarin Pharmaceutical Inc. and Shire. K Belani was a co-investigator on several studies funded by grants from Lysogene and Shire and has received a travel grant from BioMarin Pharmaceutical Inc. for attendance at an advisory meeting. H Amartino has conducted investigator, speaker and consultant work for Amicus, BioMarin Pharmaceutical Inc., Bluebird Bio, Sanofi Genzyme and Shire. K Berger has received consultancy and honoraria payments from BioMarin Pharmaceutical Inc. and Sanofi Genzyme. Andrea Borgo has received travel grants and honoraria from BioMarin Pharmaceutical Inc., and honoraria from Brains for Brains and Shire. E Braunlin has received speaker and travel grants from BioMarin Pharmaceutical Inc. and Sanofi Genzyme, a research funding from BioMarin Pharmaceutical Inc. and Bluebird Bio and has conducted consultancy work for Ultragenyx. Y Eto has received research grants and honoraria from BioMarin Pharmaceutical Inc., Alexion Pharmaceutical Inc., Sanofi Genzym and Actelion Pharmaceuticals Ltd., and honoraria from Dainippon Sumitomo Inc., Japan Chemical Research and Shire Japan. JI Gold has received honoraria and travel grants from BioMarin Pharmaceutical Inc. A Jester has received honoraria, travel grants, and research funding from BioMarin Pharmaceutical Inc. and funding from Shire for equipment to conduct outcomes assessment. S Jones has conducted investigator, speaker and consultancy work for Alexion, BioMarin Pharmaceutical Inc., Orchard therapeutics, Sanofi Genzyme, Shire and Ultragenyx. C Karsli has nothing to disclose. W MacKenzie has received travel grants and honoraria from BioMarin Pharmaceutical Inc. and has conducted consultancy work for Johnson & Johnson. A McFadyen has received unrestricted educational grants from Alexion, BioMarin Pharmaceutical Inc., Sanofi Genzyme, Shire, and Johnson and Johnson. J McGill has conducted speaker, consultancy, board member work and received travel grants from Actelion, BioMarin Pharmaceutical Inc., Sanofi Genzyme and Shire. He has been an investigator for BioMarin Pharmaceutical Inc. J Mitchell has received research support, advisory board fees, and travel grants from BioMarin Pharmaceutical Inc. and has been involved in the conduct of BioMarin clinical trials. He has also received research funding from Sanofi Genzyme and Shire. He has received consultancy fees from Ultragenyx, BioMarin Pharmaceutical Inc., Sanofi Genzyme and Shire. J Muenzer has conducted consultancy work and/ or has received grant support from BioMarin Pharmaceutical Inc., Denali, Green Cross, Eloxx, PTC Therapeutics, RegenXbio, Sangamo, Sanofi Genzyme, Shire and Sobi. T Okuyama has received research grants from BioMarin Pharmaceutical Inc., Green Cross, Sanofi Genzyme, Shire, Orchard Therapeutics, and JCR, and has attended advisory boards for Sanofi Genzyme. He is Principal Investigator for ERT clinical trials for MPS II sponsored by Green Cross and JCR. P Orchard has received honoraria, travel and research support from Sanofi Genzyme, and has received research support from BioMarin Pharmaceutical Inc., Bluebird Bio and Horizon Pharma. B Stevens has received grants for the MPS Society from Sanofi Genzyme, Shire, Sangamo, Regenxbio, BioMarin Pharmaceuticals Inc. and Ultragenyx for direct advocacy, expert meetings, literature and travel. S Thomas has received grants for the MPS Society from Sanofi Genzyme, Shire, Sangamo, Regenxbio, BioMarin Pharmaceuticals Inc., Chiesi and Ultragenyx for direct advocacy, expert meetings, honoraria, literature and travel. DR Marinho has received honoraria and travel grants from BioMarin Pharmaceutical Inc. R Walker has received travel grants, honorarium and payments for consulting work from BioMarin Pharmaceutical Inc., Sanofi Genzyme and Shire. R Wynn has conducted consultancy work for Chimerix, Bluebird Bio and Orchard Therapeutics.
© 2019 The Author(s).
- Elosulfase alfa
- Enzyme replacement therapy
- Haematopoietic stem cell transplantation
- MPS IVA
- Management guidelines
- Morquio a syndrome