High Disease Burden and a Need for New Treatments in Congenital Adrenal Hyperplasia (CAH): Results of a Structured Literature Review

Presentation Number: SUN 404
Date of Presentation: April 2nd, 2017

John Porter*1, Michael Withe1, Catherine Rycroft2 and Uzmah Sabar2
1Diurnal Limited, Cardiff, United Kingdom, 2BresMed, Sheffield, United Kingdom


Introduction: CAH are a group of rare autosomal-recessive disorders arising from genetic defects in cortisol biosynthesis. The most frequent type of CAH is 21-hydroxylase deficiency (21OHD) defined as either classic 21OHD CAH (cortisol insufficiency) or non-classic 21OHD CAH (partial or normal cortisol production). Classic 21OHD CAH is characterised by elevated androgen levels and ambiguous genitalia in affected females.

Objectives: We performed this literature review to identify the disease burden and treatment landscape in CAH, with specific focus on classic 21OHD CAH (herein referred to as C-CAH).

Methods: A structured, comprehensive literature review was conducted to identify articles describing the burden and treatment landscape of CAH, including: epidemiology; natural history; clinical characteristics; humanistic and economic burden; treatment options, and current clinical guidelines. Global literature databases, guideline databases, regulatory and health technology assessment agency websites, relevant society guidelines, trial registries and relevant conference proceedings were all searched for relevant data. Eligible articles were those reporting on CAH, and providing data on at least one topic of interest.

Results: A total of 2,204 citations were identified, 226 of which were selected for final inclusion. Articles reporting on C-CAH covered the following topics: natural history (6); epidemiology (22); humanistic burden (including symptoms and cardiovascular risk [27], quality of life [33] and caregiver burden [8]); resource burden (3) and clinical guidelines (5). Epidemiology data confirmed the ultra-orphan nature of this disease. Humanistic burden data reported substantial patient burden with C-CAH patients commonly experiencing sexuality, infertility and psychological issues. C-CAH also had a negative impact on family and carer quality of life, especially parents of paediatric patients. No articles reported on the overall economic burden associated with C-CAH. Regarding treatment management of C-CAH, identified clinical guidelines recommended glucocorticoid and mineralocorticoid replacement therapy. Furthermore, guidelines recommended the development of alternative steroid replacement regimens that minimise daily glucocorticoid exposure and compared to current therapies, are better at simulating normal physiological cortisol secretion.

Discussion: To our understanding, this is the first comprehensive structured literature review describing the disease burden and treatment profile in C-CAH. Our review has highlighted that C-CAH is associated with a substantial patient and caregiver burden. Furthermore, the lack of available data on the overall economic burden of C-CAH warrants further study. Of importance, the recommendation of clinical guidelines for the development of new treatment options in C-CAH should be noted.


Disclosure: JP: Employee, Diurnal. MW: Employee, Diurnal. CR: Consultant, Diurnal. US: Consultant, Diurnal.