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 In- Process (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