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
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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.
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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)