IMPACT OF TREATMENT STATUS ON EQ-5D-5L UTILITIES IN ALPHA-MANNOSIDOSIS: A VIGNETTE STUDY
Author(s)
Andrew Lloyd, DPhil1, Karolina M. Stepien, MD, PhD2, Timothy M. Cox, MD, FRCP, FMedSci3, Uma Ramaswami, FRCPCH, MD4, Duncan Cole, PhD, MRCP, FRCPath, FHEA5, Elizabeth Morris, RN6, Michelle Tharp, DNP, FNP-BC7, Chiara Donati, MD8, Heather Morgan, PhD9, Kamran Iqbal, MBBS, MRCP10, Jacqui Bernarde, MSc1, Caleb Dixon, MSc1, Khashayar Azimpour, MD, PhD11.
1Acaster Lloyd, London, United Kingdom, 2Adult Inherited Metabolic Diseases, Salford Royal Hospital, Northern Care Alliance NHS Foundation Trust, Salford, United Kingdom, 3Lysosomal Disorders Unit, Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom, Cambridge, United Kingdom, 4Institute of Infection, Immunity and Rare Diseases Royal Free London NHS Foundation Trust, London, United Kingdom, 5Cardiff University School of Medicine, Centre for Medical Education, College of Biomedical and Life Sciences, University Hospital of Wales, Cardiff, United Kingdom, 6Inherited Metabolic Disease Service, Cambridge University Hospitals, Cambridge, United Kingdom, 7University of Mississippi Medical Center, Jackson, MS, USA, 8Chiesi Farmaceutici S.p.A., Parma, Italy, 9Chiesi USA, Inc, Boston, NY, USA, 10Chiesi Limited, Manchester, United Kingdom, 11Chiesi Canada Corp, Woodbridge, ON, Canada.
1Acaster Lloyd, London, United Kingdom, 2Adult Inherited Metabolic Diseases, Salford Royal Hospital, Northern Care Alliance NHS Foundation Trust, Salford, United Kingdom, 3Lysosomal Disorders Unit, Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom, Cambridge, United Kingdom, 4Institute of Infection, Immunity and Rare Diseases Royal Free London NHS Foundation Trust, London, United Kingdom, 5Cardiff University School of Medicine, Centre for Medical Education, College of Biomedical and Life Sciences, University Hospital of Wales, Cardiff, United Kingdom, 6Inherited Metabolic Disease Service, Cambridge University Hospitals, Cambridge, United Kingdom, 7University of Mississippi Medical Center, Jackson, MS, USA, 8Chiesi Farmaceutici S.p.A., Parma, Italy, 9Chiesi USA, Inc, Boston, NY, USA, 10Chiesi Limited, Manchester, United Kingdom, 11Chiesi Canada Corp, Woodbridge, ON, Canada.
OBJECTIVES: Alpha-mannosidosis (AM) is an ultra-rare lysosomal disorder associated with progressive cognitive, sensory, skeletal, and mobility-related impairment. AM manifests across a continuum of clinical severity from childhood through adulthood. Although enzyme replacement therapy (ERT) with velmanase alfa is available for non-neurological manifestations in patients with mild-to-moderate AM, there is limited evidence of the effects of impaired mobility and ERT on health-related quality of life. Here we estimate EQ-5D-5L utilities for AM health states and compare treated with untreated vignettes in adults and children.
METHODS: AM health states were defined by age group, mobility level, and ERT status. Adult and child vignettes described four mobility categories that align with a previously developed cost-utility analysis framework: (1) normal walking, (2) occasional walking aid/wheelchair use, (3) frequent walking aid/wheelchair use, and (4) wheelchair dependent, each as treated or untreated. After validation by six clinicians and four caregivers, vignettes were evaluated by a UK general population sample using EQ-5D-5L. Linear mixed models, fitted separately for adult and child states, assessed mobility level, treatment status, and their interaction; treated versus untreated states were compared using Tukey-adjusted contrasts.
RESULTS: Treated states had higher EQ-5D-5L utilities across most AM health states. In adult vignettes, utilities were significantly higher for treated versus untreated states across all mobility levels, with gains from +0.079 to +0.319 (all p<0.001). In child vignettes, treated utilities were significantly higher for occasional walking aid/wheelchair use, frequent walking aid/wheelchair use, and wheelchair dependent, with gains from +0.091 to +0.342 (all p<0.001), but not for normal walking (+0.017; p=0.48).
CONCLUSIONS: EQ-5D-5L utilities suggest that ERT with velmanase alfa is associated with meaningful HRQoL benefits in AM, particularly among patients with impaired mobility. We envisage that these utility values can be used to inform future evaluation and make the case for timely initiation of ERT.
METHODS: AM health states were defined by age group, mobility level, and ERT status. Adult and child vignettes described four mobility categories that align with a previously developed cost-utility analysis framework: (1) normal walking, (2) occasional walking aid/wheelchair use, (3) frequent walking aid/wheelchair use, and (4) wheelchair dependent, each as treated or untreated. After validation by six clinicians and four caregivers, vignettes were evaluated by a UK general population sample using EQ-5D-5L. Linear mixed models, fitted separately for adult and child states, assessed mobility level, treatment status, and their interaction; treated versus untreated states were compared using Tukey-adjusted contrasts.
RESULTS: Treated states had higher EQ-5D-5L utilities across most AM health states. In adult vignettes, utilities were significantly higher for treated versus untreated states across all mobility levels, with gains from +0.079 to +0.319 (all p<0.001). In child vignettes, treated utilities were significantly higher for occasional walking aid/wheelchair use, frequent walking aid/wheelchair use, and wheelchair dependent, with gains from +0.091 to +0.342 (all p<0.001), but not for normal walking (+0.017; p=0.48).
CONCLUSIONS: EQ-5D-5L utilities suggest that ERT with velmanase alfa is associated with meaningful HRQoL benefits in AM, particularly among patients with impaired mobility. We envisage that these utility values can be used to inform future evaluation and make the case for timely initiation of ERT.
Conference/Value in Health Info
2026-11, ISPOR Europe 2026, Vienna, Austria
Value in Health, Volume 29, Issue 12S
Code
PCR82
Topic
Patient-Centered Research
Topic Subcategory
Health State Utilities, Patient-reported Outcomes & Quality of Life Outcomes
Disease
Rare & Orphan Diseases