Healthcare resource use and costs of managing children and adults with lysosomal acid lipase deficiency at a tertiary referral centre in the United Kingdom

PLOS ONE, Nov 2019

Objective To estimate clinical progression and resource utilisation together with the associated costs of managing children and adults with LAL Deficiency, at a tertiary referral centre in the UK. Methods A retrospective chart review was undertaken of patients in the UK with a confirmed diagnosis of LAL Deficiency who were managed at a LAL Deficiency tertiary referral treatment centre. Patients’ pathways, treatment patterns, health outcomes and resource use were quantified over differing lengths of time for each patient enabling the NHS cost of patient management in tertiary care to be estimated. Results The study population comprised 19 patients of whom 58% were male. Mean age at the time of initial presentation was 15.5 years and the mean age at diagnosis was 18.0 years. 63%, 53% and 42% of patients had hepatomegaly, abnormal lipid storage and splenomegaly at a mean age of presentation of 17.8, 17.1 and 20.9 years, respectively. Over a period of 50 years there were a mean of 48.5 clinician visits and 3.4 hospital admissions per patient. The mean NHS cost of patient management at a LAL Deficiency tertiary referral treatment centre, spanning a period of over 50 years was £61,454 per patient. Conclusion This study provides important insights into a number of aspects of the disease that are difficult to ascertain from published case reports. Additionally, it provides the best estimate available of NHS resource use and costs with which to inform policy and budgetary decisions pertaining to managing this ultra-orphan disease.

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Healthcare resource use and costs of managing children and adults with lysosomal acid lipase deficiency at a tertiary referral centre in the United Kingdom

February Healthcare resource use and costs of managing children and adults with lysosomal acid lipase deficiency at a tertiary referral centre in the United Kingdom Julian F. Guest 0 Andy Ingram 0 Nadia Ayoub 0 Christian J. Hendriksz Elaine Murphy Yusof Rahman Patrick McKiernan Helen Mundy 1 Patrick Deegan Kimon Bekelis, Dartmouth-Hitchcock Medical Center, UNITED STATES 0 Catalyst Health Economics Consultants , Rickmansworth, Hertfordshire , United Kingdom , 2 Faculty of Life Sciences and Medicine, King's College , London , United Kingdom , 3 Adult Inherited Metabolic Disorders , Salford Royal NHS Foundation Trust , Salford , United Kingdom , 4 Paediatrics and Child Health , University of Pretoria , Pretoria , South Africa , 5 Charles Dent Metabolic Unit, National Hospital for Neurology and Neurosurgery , London , United Kingdom , 6 Adult Inherited Metabolic Disease , Guy's & St Thomas' Hospital , London , United Kingdom , 7 The Liver Unit, Birmingham Children's Hospital , Birmingham , United Kingdom 1 Evelina Children's Hospital, Guy's & St Thomas' Hospital , London , United Kingdom , 9 Lysosomal Disorders Unit, Addenbrooke's Hospital , Cambridge , United Kingdom - mean NHS cost of patient management at a LAL Deficiency tertiary referral treatment centre, spanning a period of over 50 years was £61,454 per patient. a1111111111 a1111111111 a1111111111 a1111111111 a1111111111 OPEN ACCESS Data Availability Statement: Data are not publicly available because of the risk that individual patients could be identified due to the small sample size. This restriction was a condition of the Ethics approval by NRES Committee North East - Tyne & Wear South (reference no: 14/NE/1186). Data from this study can be obtained from Catalyst Health Economics Consultants (info@catalyst-health. com). Objective Methods Results Funding: This study was part funded by Synageva Biopharma Corp, Lexington, MA, US, now part of Alexion Pharmaceuticals Inc., Cheshire, CT, US. However, the funders had no role in study design, data collection and analysis or preparation of the manuscript. The funders commissioned Catalyst Health Economics Consultants (Catalyst) to conduct the study. However, the funders did not provide support in the form of salaries for Catalyst employees. Competing interests: All the authors certify that they have no affiliation with or financial involvement in any organisation or entity with a direct financial interest in the subject matter or materials discussed in this manuscript. Elaine Murphy and Patrick Deegan were consultees to The National Institute for Health and Care Excellence Evaluation Committee on sebelipase alfa for treating LAL Deficiency. Christian J Hendriksz, Elaine Murphy, Yusof Rahman, Helen Mundy and Patrick Deegan were investigators in clinical trials of sebelipase alfa. The authors have no other conflicts of interest that are directly relevant to the content of this manuscript and this does not alter the authors' adherence to PLOS ONE policies on sharing data and materials. Abbreviations: LAL, Lysosomal acid lipase; NHS, National Health Service; UK, United Kingdom. Conclusion This study provides important insights into a number of aspects of the disease that are difficult to ascertain from published case reports. Additionally, it provides the best estimate available of NHS resource use and costs with which to inform policy and budgetary decisions pertaining to managing this ultra-orphan disease. Introduction LAL Deficiency (also called cholesterol ester storage disease OMIM 27800) is an autosomal recessive disorder caused by a deficiency of the enzyme, cholesterol ester hydrolase (EC 3.1.1.13). It can manifest as a severe infantile and rapidly progressive disorder, Wolman's disease, or the more attenuated form which manifests in childhood or adolescence as a progressive disease affecting many organ systems, which is the scope of this article [ 1,2 ]. The infantile variant of the disease is characterised by harmful amounts of lipids that accumulate in the liver, spleen, bone marrow, small intestine, adrenal glands, and lymph nodes leaving affected infants suffering from severe malabsorption, failure to thrive, severe liver dysfunction and high rates of mortality. LAL Deficiency in infants has an estimated incidence of between 1 in 350,000 and 1 in 512,000 newborns. These children are estimated to die of the disease at a median age of 3.6 months [ 3,4 ]. The less rapidly progressive presentation of LAL Deficiency, often referred to as Cholesteryl Ester Storage Disease and which is the focus of this study, affects both children and adults and has been estimated to affect 3±25 individuals per million worldwide [ 5 ]. The median age of first symptoms is around 5 years of age, although many patients remain misdiagnosed or undiagnosed, since symptoms and signs overlap with more common hepatic conditions [ 1,6 ]. Other patients remain asymptomatic in spite of extensive underlying p (...truncated)


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Julian F. Guest, Andy Ingram, Nadia Ayoub, Christian J. Hendriksz, Elaine Murphy, Yusof Rahman, Patrick McKiernan, Helen Mundy, Patrick Deegan. Healthcare resource use and costs of managing children and adults with lysosomal acid lipase deficiency at a tertiary referral centre in the United Kingdom, PLOS ONE, 2018, Volume 13, Issue 2, DOI: 10.1371/journal.pone.0191945