7061 Incidence of Adrenal Crisis In Congenital Adrenal Hyperplasia (CAH) Patients During A Prospective Monitored Long-Term Study Of Modified-Release Hydrocortisone (MRHC) Capsules, (Efmody)

Abstract

Abstract Disclosure: R.J. Ross: Consulting Fee; Self; Diurnal. D.P. Merke: Research Investigator; Self; Diurnal. A. Mallappa: Research Investigator; Self; Diurnal. W. Arlt: Research Investigator; Self; Diurnal. A. Brac de la Perriere: Research Investigator; Self; Diurnal. A.L. Hirschberg: Research Investigator; Self; Diurnal. J.D. Newell-Price: Research Investigator; Self; Diurnal. A. Prete: Research Investigator; Self; Diurnal. A. Rees: Research Investigator; Self; Diurnal. N. Reisch: Research Investigator; Self; Diurnal. M. Quinkler: Research Investigator; Self; Diurnal. P.A. Touraine: Research Investigator; Self; Diurnal. K. Maltby: Employee; Self; Diurnal. J. Quirke: Employee; Self; Diurnal. N. Aslam: Employee; Self; Diurnal. H. Coope: Employee; Self; Diurnal. J. Porter: Employee; Self; Diurnal. Background: Adrenal crisis is the leading cause of excess mortality in patients with CAH[1]. Retrospective studies report an adrenal crisis incidence of 5-10/100 patient years (PY), with mortality 0.5/100 PY2. Modified-release hydrocortisone (MRHC) capsules, (Efmody), replicate cortisol diurnal rhythm and improve androgen control in CAH compared to standard glucocorticoid therapy2. Here, we report the incidence of adrenal crisis in CAH patients from a prospective study of MRHC in CAH patients. Methods: Patients completing MRHC Ph2 and Ph3 studies were eligible to enter a single-arm, open-label extension study. Study visits occurred at baseline, weeks 4, 12, 24 and 6-monthly thereafter. The primary endpoint was the safety of MRHC over time. Adrenal crisis was defined according to Allolio 20153. MRHC doses were adjusted on the basis of an adrenal insufficiency checklist, and measurement of androstenedione (A4) and 17-hydroxyprogesterone (17-OHP) at 9am and 1pm. Results: 91 patients entered the study, mean age 37 years, 68% female, 32% male. 22 discontinued; 11 at patient request, 5 due to pregnancy, 2 undergoing fertility treatment, 2 at physician/sponsor request, 1 due to an AE (carpal tunnel syndrome), and 1 due to death (myocardial infarction). Median treatment duration was 1500 days, range 0.2 to 5.8 years. Median MRHC dose at study entry was 30mg/day, reducing to 20mg/day from 24-weeks until end of study. Signs and symptoms of adrenal insufficiency due to under-treatment were reported for 41 (45.1%) participants, most frequently fatigue which was reported at some point by 41.8% of all participants. Signs and symptoms of overtreatment were reported for 25 (27.5%) participants, most frequently sudden weight gain which was reported at some point by 16.5% of all participants. Signs and symptoms of both over- and undertreatment occurred predominantly during the first 24 weeks. The study encompassed 357 participant years, and 18 adverse events considered indicative of adrenal crisis occurred in 7 participants, giving an incidence rate of 5.043 adrenal crises / 100 PY. Conclusions: Data from this longest prospectively monitored study in CAH suggest that the incidence of adrenal crisis on MRHC is at the low end of that reported in retrospective studies and the safety profile of MRHC is otherwise similar to immediate release hydrocortisone.