The effectiveness and cost of enzyme replacement and substrate reduction therapies: a longitudinal cohort study of people with lysosomal storage disorders

List of abbreviations Executive summary Background Objectives Methods Results Conclusions Recommendations for research Funding Chapter 1 Background Lysosomal storage disorders Summary of lysosomal storage disorders investigated in this study Patterns of treatment in England Rationale for the cohort study Background and objectives Chapter 2 Methods Study procedures Data collection Methods used in analysis Key for longitudinal model outputs Cost data analysis methods Changes to original protocol Chapter 3 Results – Gaucher disease Patient characteristics Key markers of Gaucher disease progression Summary of Gaucher disease results Platelet count Haemoglobin Bone pain Spleen volume Clinical enlargement of spleen (adults) Liver size Liver from scan and palpation Liver function tests Neurological involvement Quality-of-life assessments Fatigue Severity Scale Carer Strain Index Safety and complications Cost of ERT in people with Gaucher disease Cost of care for adults with Gaucher disease Cost of care for children with Gaucher disease Discussion of Gaucher disease results Chapter 4 Results – Fabry disease Patient characteristics Key markers of Fabry disease progression Summary of analysis Summary of results Heart size – left ventricular mass index Renal function – estimated glomerular filtration rate Proteinuria Brief Pain Inventory Audiology – use of a hearing aid Neurology – transient ischaemic attack/stroke Quality-of-life assessments Comparison of the effectiveness of agalsidase alpha and agalsidase beta in Fabry disease Heart size – left ventricular mass index Renal function – estimated glomerular filtration rate Proteinuria Brief Pain Inventory Audiology – use of hearing aid Neurology – transient ischaemic attack/stroke Safety and complications Cost of enzyme replacement therapy in people with Fabry disease Cost of care for adults with Fabry disease Cost of care for children with Fabry disease Discussion of Fabry disease results Chapter 5 Results – mucopolysaccharidosis type I (MPS I) Patient characteristics Key markers of disease progression for mucopolysaccharidosis type I Summary of results Per cent of predicted forced vital capacity Mobility Hearing Height in children Weight Cardiac valve involvement Carpal tunnel syndrome Developmental quotient score (children) Cervical cord compression Palpable splenic enlargement Palpable liver enlargement Quality-of-life assessments Fatigue Severity Scale Carer Strain Index Safety and complications Cost of enzyme replacement therapy in people with MPS I Cost of care for adults with MPS I Cost of care for children with MPS I Discussion of MPS I results Chapter 6 Results – mucopolysaccharidosis type II (MPS II) Patient characteristics Key markers of disease progression Summary of results Per cent of predicted forced vital capacity Mobility 6-minute walk test Height Weight Hearing Cardiac valve involvement Carpal tunnel syndrome Palpable splenic enlargement Palpable liver enlargement Quality-of-life assessments Safety and complications Cost of enzyme replacem nt therapy in people with MPS II Cost of care for adults with MPS II Cost of care for children with MPS II Discussion of MPS II results Chapter 7 Res lts – P mpe dise se Patient charact ristics Key markers f disease progression Summary of results Per cent of predicted forced vital capacity Ventilation Swallowing Mobility 6-minute walk test Muscle strength test Body mas index Height Weight Quality-of-life assessments Safety and complications Cost of enzyme replacement therapy in people with Pompe disease Cost of care for adults with Pompe disease Cost of care for children with Pompe disease Discussion of Pompe di ease results Chapter 8 Results – Niemann–Pick disease type C (NPC) Patie t ch racteristics Key markers of disease progression Summary of results Height in children Weight Central nervous sy tem measures Quality-of-life assessments Safety and complications Cost of substrate reduction therapy in people with NPC Cost of care for adults with NPC Cost of c re for children with NPC Discu sion of NPC results Chapter 9 Discussion Costs associated with lysosomal storage disorders Study strengths and limitations Chapter 10 Conclusion Acknowledgeme ts Contribution of authors