CONFIDENTIAL
SUN 404, Sunday 2 April 2017
High Disease Burden and a Need for
New Treatments in Congenital Adrenal
Hyperplasia (CAH): Results of a
Structured Literature Review
John Porter,1a Michael Withe,1a Catherine Rycroft,2 and Uzmah Sabar.2
1Diurnal
Limited, Cardiff, England, UK; 2BresMed, Sheffield, England, UK.
Introduction and Aims
 Congenital adrenal hyperplasia (CAH) is a group of rare autosomal-recessive
disorders arising from genetic deficiencies in key enzymes involved in cortisol
synthesis1
 The most common form of CAH is 21-hydroxylase deficiency (21-OHD), which
is due to mutations in the CYP21A2 gene1
 21-OHD CAH can be defined as either classic 21-OHD CAH (cortisol
insufficiency) or non-classic 21-OHD CAH (partial or normal cortisol
production)2
− Classic 21-OHD CAH is characterised by elevated androgen levels, ambiguous
genitalia in newborn females and postnatal virilisation in both males and
females3
 This structured literature review aimed to identify the disease burden and
treatment landscape in CAH (excluding publications reporting on non-classic
21-OHD only)
Methodology
 Database search
 MEDLINE (via Embase.com); Embase (via Embase.com); MEDLINE InProcess (via PubMed); EconLit (via EBSCO); and the Cochrane Library
− Searches were conducted for articles published between 2006 and 2016
− Searches were restricted to articles published in English and studies
conducted in humans only. Searches excluded comments, letters, news
articles and editorials
 Additional searches were conducted in a variety of websites (Table 1)
 Inclusion criteria were:
− Adults and children with CAH
− Presented information on at least one of: risk factors;
disease progression; epidemiology; humanistic
burden (including symptoms and comorbidities,
HRQL and caregiver burden); resource use and
economic burden; current clinical management; and
clinical guidelines
 Data were extracted from all included publications
Results- papers identified
Results: Burden of Disease
 The literature indicated that patients with CAH
− were significantly shorter than the normal population
− had fertility issues such as menstrual cycle irregularities
− had impaired bone metabolism
− had raised blood pressure profiles
− had a significantly reduced HRQL compared with controls
− were more likely to suffer from psychological illnesses such as attention
deficit hyperactivity disorder, anxiety and depression.
 Eight articles reported that there is a substantial caregiver burden
associated with CAH.
− parents as the primary carers reported a ‘latent anxiety’ as well as
a disruption to their daily routines and their work life
Clinical Guidelines
 Clinical guidelines
− recommend glucocorticoid and mineralocorticoid replacement therapy
for CAH
−
two guidelines state a need for the development of novel steroid
replacement regimens that are better at simulating normal physiological
cortisol secretion compared with current therapies
Conclusions
 Key findings of this literature review are:
− Patients with CAH present a high disease burden to society
− Although limited, the data indicates a substantial caregiver burden in
CAH
− Publications reporting on the economic burden of CAH are sparse;
considering the huge disease burden, costs are likely to be significant
and should be explored
− Current clinical management of CAH involves a multidisciplinary team
 Furthermore, the specific recommendations for the development of new
treatment options in CAH in clinical guidelines should be considered
important
 To our knowledge, this is the first comprehensive structured literature review
describing the disease burden and treatment profile in CAH