Evidence-based, expert-agreed recommendations for the management of patients with MPS IVA/VI: Recommendations to replace the specific missing enzyme

Management of mucopolysaccharidosis (MPS) is complicated, therefore robust independent guidance is required. This program used a modified-Delphi methodology to develop evidence-based, expert-agreed recommendations for the management of patients with MPS IVA/VI. The program was led by an international, multidisciplinary Steering Committee (SC) of 29 MPS experts. Following a systematic literature review process, the SC developed 117 recommendation statements covering general principles, routine monitoring and assessments, interventions to treat the underlying disease and surgical interventions. The statements were ratified using a blinded modified-Delphi online survey in which they were rated using a Likert scale by international MPS physicians. Consensus was reached when ≥75% respondents agreed with a given statement and following two rounds of voting, all 117 statements reached consensus. During this process, the MPS community voted upon the use of enzyme replacement therapy (ERT) and hematopoietic stem cell therapy (HSCT) to address the underlying enzyme deficiency in patients with MPS IVA/VI. For each treatment the rationale, evidence base and deliberations for management (including safety and efficacy, monitoring response and adverse events) were considered at length. The expert consensus determined that the risk-profile benefit of HSCT in patients with MPS IVA/VI is less clear than in other types of MPS, and further research, including a comparative study to better understand the long-term efficacy and safety of HSCT is required. Therefore, initiation of long-term ERT is currently recommended as soon as possible after diagnosis for patients with MPS IVA/VI. Whilst HSCT is not currently recommended in patients with MPS IVA due to limited evidence, HSCT may be an option for patients with MPS VI with consideration of the associated safety risks, donor status and institution experience. Further research is required to address evidence gaps and to determine the long-term outcomes of ERT and HSCT in patients with MPS IVA/VI.