Objective: Patients with classic congenital adrenal hyperplasia (CAH) often require supraphysiologic doses of glucocorticoids to replace missing cortisol and reduce adrenal androgens. Current treatments aim to control androgen-driven symptoms/impacts but can result in glucocorticoid-related side effects/complications. This study aimed to understand the preferences of adults with classic CAH for the benefits of a potential new adjunctive therapy that could provide better androgen control with lower glucocorticoid doses via an online discrete choice experiment (DCE).

Methods: Relevant data and qualitative literature were reviewed and eight adults with classic CAH were interviewed to understand disease and treatment experience. This informed development of seven attributes that reflected hypothetical adjunctive therapy benefits. Following input from two endocrinologists, cognitive testing with three adults with classic CAH and a pilot launch, DCE survey data collected from 118 adults with classic CAH were analyzed using conditional logit regression.

Results: Initial qualitative interviews (N=8, 50% female, age 19­–67) revealed medication management was the main daily impact of classic CAH. Participants were accustomed to self-managing multiple medications/doses and most were willing to try an additional, twice-daily medication that addressed their top five symptoms/impacts or side effects/complications. The DCE (N=118, 75% female, age 19–69) revealed the following adjunctive treatment priorities (all coefficients p<0.001 vs baseline of no change): complete avoidance of glucocorticoid-driven weight gain (1.109); moderate decrease in risk of developing glucocorticoid-related long-term complications: type 2 diabetes (0.540), osteopenia, osteoporosis, fractures (0.521) and cardiovascular disease (0.502); moderate improvement in fatigue (0.439), fertility (0.437), and hirsutism (females only) and acne (0.410).

Conclusions: Adults with classic CAH valued avoidance of glucocorticoid-driven weight gain by twice the magnitude of other potential benefits. Reduced risk of glucocorticoid-driven side effects was valued over improvements in fatigue, fertility and hirsutism/acne. These preference patterns may inform where new therapies have a meaningful impact on patients.