Modified-release Hydrocortisone Research Articles

Comparison of modified-release hydrocortisone capsules versus prednisolone in the treatment of congenital adrenal hyperplasia.

Prednisolone and prednisone are recommended treatment options for adults with Congenital Adrenal Hyperplasia (CAH); however, there is no randomised comparison of prednis(ol)one with hydrocortisone. To assess 17-hydroxyprogesterone (17OHP) levels and glucocorticoid dose in CAH comparing prednis(ol)one versus modified-release hydrocortisone (MRHC). Six-month open-label randomised phase 3 study and interim analysis of a single-arm extension study. Hydrocortisone dose equivalent and 09:00h 17OHP from 48 patients taking prednis(ol)one at baseline. At baseline, the median hydrocortisone dose equivalent was 30 mg /day and 17OHP was <36nmol/l (3X upper limit of normal) in 56% of patients. Patients were randomised to continue prednis(ol)one or switch to MRHC at the same hydrocortisone equivalent dose. At 4 weeks, 94% on MRHC and 71% on prednis(ol)one had 17OHP <36nmol/l. At 18 months in the extension study of MRHC, the median MRHC dose was 20 mg /day and 82% had 17OHP <36nmol/l. The percent of patients with 17OHP <36nmol/l on a hydrocortisone dose equivalent ≤25mg /day was greater at 18 months in the extension study on MRHC than while on prednis(ol)one at baseline: 57% vs 27%, P=0.04. In the randomised study, no patients had an adrenal crisis on MRHC and one on prednisolone. In the extension study (221 patient years), there were 12 adrenal crises in 5 patients (5.4/100 patient years). MRHC reduces 17OHP at 09:00h compared to prednis(ol)one and the dose of MRHC can be down-titrated over time in the majority of patients.

Modified release hydrocortisone, a new treatment for congenital adrenal hyperplasia due to 21-hydroxylase deficiency: a single center 'real-world evidence' preliminary study

Modified release hydrocortisone, a new treatment for congenital adrenal hyperplasia due to 21-hydroxylase deficiency: a single center 'real-world evidence' preliminary study

Fertility outcomes in women with classic and non-classic congenital adrenal hyperplasia on modified-release hydrocortisone (MR-HC)

Fertility outcomes in women with classic and non-classic congenital adrenal hyperplasia on modified-release hydrocortisone (MR-HC)

Incidence of adrenal crisis in Congenital Adrenal Hyperplasia (CAH) patients during a prospective monitored long-term study of modified-release hydrocortisone (MRHC) capsules, (Efmody)

Incidence of adrenal crisis in Congenital Adrenal Hyperplasia (CAH) patients during a prospective monitored long-term study of modified-release hydrocortisone (MRHC) capsules, (Efmody)

Impact on immunophenotype of switching from conventional glucocorticoids to modified-release hydrocortisone in congenital adrenal hyperplasia

Impact on immunophenotype of switching from conventional glucocorticoids to modified-release hydrocortisone in congenital adrenal hyperplasia

Enhanced well-being in patients with congenital adrenal hyperplasia on modified-release hydrocortisone compared to conventional glucocorticoid replacement

Enhanced well-being in patients with congenital adrenal hyperplasia on modified-release hydrocortisone compared to conventional glucocorticoid replacement

In Vitro Profile of Hydrocortisone Release from Three-Dimensionally Printed Paediatric Mini-Tablets.

Three-dimensional (3D) printing is quickly being adopted in pharmaceutics due to the many advantages it offers, including treatment, adaptability, the reduction in waste and the accelerated development of new formulations. In this study, micro-extrusion printing was implemented for the production of modified-release hydrocortisone (HCT) mini-tablets for paediatric patients. For the developed formulations, Gelucire® 44/14 and Precirol® ATO 5 were used as the main inks at three different ratios: 70%/30%, 60%/40% and 50%/50%, respectively. The printing parameters (temperature and pressure) were altered accordingly for each ratio to achieve printability. The printed mini-tablets exhibited excellent printing quality, featuring consistent layer thicknesses and smooth surfaces. Dissolution tests were performed, and the results indicated a successful modified release of HCT from the mini-tablets. In summary, micro-extrusion exhibited favourable processing abilities for powder blends, facilitating quick printing and the fabrication of potential personalized dosages.

Course of COVID-19 infection in patients with congenital adrenal hyperplasia.

Patients with primary adrenal insufficiency due to congenital adrenal hyperplasia (CAH) are at risk for adrenal crisis during infectious illnesses. Increased risk of infection including COVID-19 has been variably reported. To evaluate COVID-19 illness outcomes and stress dose practices in a large cohort of patients with CAH during the first two years of the pandemic and compare observations of COVID-19 infection in patients with CAH to the general USA population. Between March 2020 and November 2022, patients with CAH followed at the National Institutes of Health Clinical Center were queried about COVID-19 infection during their routine visits. Cases of COVID-19 were compared to controls. COVID-19 infection rates and symptoms were compared to general USA population data from the Centers for Disease Control and Prevention. Of 168 patient visits, there were 54 (32%) cases of COVID-19 infection, and 15 (28%) were pediatric. Overall an association was found between acquiring COVID-19 and obesity (p=0.018), and adults acquiring COVID-19 were on lower doses of fludrocortisone (p=0.008). Fewer cases of COVID-19 infection were reported in those receiving hydrocortisone or modified-release hydrocortisone compared to longer acting glucocorticoids (p=0.0018). In our CAH population, the pattern of COVID-19 infection rates and COVID-related symptomatology were similar to those observed in the general USA population. Most patients with the presumed alpha variant reported anosmia and ageusia, while gastrointestinal symptoms were commonly reported during the delta and omicron waves. Stress dosing occurred in 30/54 cases, and 7 received parenteral hydrocortisone. Two hospitalizations occurred; one pediatric and one adult, both with co-morbidities. There were 5 emergency room visits and no reported deaths. Patients with CAH with close follow-up do not appear to be at increased risk of acquiring COVID-19 or to have a more severe course of COVID-19 compared to the general USA population. Obesity may increase risk of acquiring COVID-19 in patients with CAH, and overall infection risk may be lower in those receiving short-acting and circadian glucocorticoid replacement therapy. Established age-appropriate guidelines for stress dosing during infectious illnesses should be used for patients with CAH and COVID-19. COVID-19 specific guidelines are not indicated. Clinical Trial Registration: ClinicalTrials.gov, identifier NCT00250159.

The use of efmody (modified-release hydrocortisone, MRHC) in patients with congenital adrenal hyperplasia (CAH): initial experience and patient feedback

The use of efmody (modified-release hydrocortisone, MRHC) in patients with congenital adrenal hyperplasia (CAH): initial experience and patient feedback

SAT304 Improved Biochemical Control With Dose Reduction In Chronic Glucocorticoid Therapy: A Phase III Extension Study Of Chronocort (Efmody) In The Treatment Of Congenital Adrenal Hyperplasia (CAH)

Abstract Disclosure: R.J. Ross: Employee; Self; Diurnal, A Neurocrine Biosciences Company. D.P. Merke: None. A. Mallappa: None. W. Arlt: None. A. Brac de la Perriere: None. A.L. Hirschberg: None. A. Juul: None. J.D. Newell-Price: None. C.G. Perry: None. A. Prete: None. A. Rees: None. N. Reisch: None. M. Stikkelbroeck: None. P.A. Touraine: None. N. Aslam: Employee; Self; Diurnal Ltd, a Neurocrine Biosciences company. H. Coope: Employee; Self; Diurnal Ltd, a Neurocrine Biosciences company. J. Porter: Employee; Self; Diurnal Ltd, a Neurocrine Biosciences Company. Background: Management of congenital adrenal hyperplasia (CAH) involves replacing cortisol deficiency and controlling raised adrenal androgens. Guidelines recommend a target daily hydrocortisone dose of ≤25mg to replace adrenal insufficiency; however, cohort studies show doses &amp;gt;25mg are used to control androgens in CAH patients. Modified-release hydrocortisone (MRHC) capsules, (Efmody, UK), replicate the cortisol diurnal rhythm and improve the control of CAH compared to standard glucocorticoid therapy1. This post-hoc analysis examines total glucocorticoid daily dose and 9am 17-hydroxyprogesterone (17-OHP) levels in MRHC treated patients after 24 months in an ongoing MRHC single-arm extension study. Methods: All patients (n=71) that completed 24 months in the extension study at the time of the interim data cut were reviewed. Patients were recruited predominantly from the 6-month randomised phase III study comparing MRHC to standard glucocorticoid with blind titration of MRHC doses. In this extension phase the dose was titrated by the investigator on the 17-OHP and androstenedione levels at 4, 12, 24 weeks and 6 monthly. Androgen control was defined as 17-OHP &amp;lt;36 nmol/L (&amp;lt;1190 ng/dL). After 24 months, 64 of the patients had 9am 17-OHP data. A Wilcoxon-signed ranks test was performed to assess the change in total MRHC daily dose from baseline to 24 months. A Fisher’s exact test was performed to determine if the number of patients that achieved androgen control on a hydrocortisone (HC) dose ≤25 mg showed a statistically significant increase. Results: The median daily HC dose at baseline was 30mg (Inter-quartile range (IQR) 25-40) and at 24 months had reduced to 20mg (IQR 15-25), p&amp;lt;0.0001.Quadrant analysis revealed the following data: Baseline: &amp;gt 36nmol/L 17-OHP &amp; &amp;lt 25mg/day 9/71 (13%). &amp;gt 36nmol/L 17-OHP &amp; &amp;gt 25mg/day18/71 (25%). &amp;lt 36nmol/L 17-OHP &amp; &amp;lt 25mg/day 22/71 (31%). &amp;lt 36nmol/L 17-OHP &amp; &amp;gt 25mg/day 22/71 (31%). 24 months: &amp;gt 36nmol/L 17-OHP &amp; &amp;lt 25mg/day 16/64 (25%). &amp;gt 36nmol/L 17-OHP &amp; &amp;gt 25mg/day 2/64 (3%). &amp;lt 36nmol/L 17-OHP &amp; &amp;lt 25mg/day 31/64 (48%). &amp;lt 36nmol/L 17-OHP &amp; &amp;gt 25mg/day 15/64 (23%). 48% of subjects achieved androgen control based on 9am 17-OHP level at a HC dose ≤ 25 mg following 24 months of MRHC treatment compared with 31% at baseline (31% vs 48%, p= 0.03 by Fisher’s exact test). Conclusions: After 24 months of MRHC treatment the median daily HC dose was reduced from a median of 30mg to 20mg and the number of patients achieving androgen control based on 9am 17-OHP while receiving HC ≤25mg/day increased significantly.

SAT296 Ambulatory 24-hour Tissue Microdialysis Of Cortisol And Metabolites, A Tool For Precision Management In Addison’s Disease

Abstract Disclosure: I. Botusan: None. K. Berinder: None. P. Methlie: None. T. Upton: None. E. Zavala: None. K. Simunkova: None. D.A. Vassiliadi: None. I. Marinelli: None. G.M. Russell: None. M.A. Grytaas: None. S. Tsagarakis: None. S.L. Lightman: None. E.S. Husebye: None. O. Kampe: None. M. Oksnes: None. S. Bensing: None. Background: The autoimmune attack on the adrenals in AD (Addison’s disease) results in lack of the vital hormones cortisol and aldosterone, rendering AD patients dependent on life-long hormone replacement therapy. Current therapies cannot replicate the physiological well-tuned, circadian and ultradian hormonal oscillations properly, probably contributing to increased mortality, morbidity and reduced quality of life. No established biomarker for treatment monitoring exists hampering treatment optimization. Ambulatory 24-hour dynamic steroid profiling may represent a novel therapy-monitoring tool, providing new insights in different replacement therapy regimes. Aim: We aimed to assess 24-hour profiles of free cortisol and metabolites in patients with AD on different glucocorticoid replacement therapies (GRT) and compare the results with healthy volunteers (HV). Material and methods: The study includes 41 patients with AD on different GRT regimes (hydrocortisone, cortisone acetate, modified release hydrocortisone) and 214 healthy participants. Twenty minute microdialysis fractions were collected ambulatory from abdominal subcutaneous tissue over 24 hours using a novel and portable microdialysis fraction collector (U-RHYTHM). Steroid hormones were analyzed by ultrasensitive liquid chromatography tandem mass spectroscopy (LC-MS/MS). Dynamic biomarkers were used to define hormone parameters in both healthy and hormone-replaced participants, and to assess the “time in range” for patients on GRT compared with the profiles of healthy controls. Results: Free cortisol and cortisone levels were measurable in all AD patients, while 18- hydroxycortisol, and corticosterone were detected only in a few AD patients suggesting the persistence of residual adrenal function. Lower cortisol levels during night were observed in AD compared with controls. Ambulatory 24-hour dynamic steroid profiling revealed marked interindividual variations partially depending on the type of GRT and dosing-regime. Conclusions: The 24-hour profiles of free cortisol and cortisone differs between patients with AD and healthy volunteers. Ambulatory 24-hour microdialysis samplings may provide a novel dynamic tool to monitor GRT in AD providing opportunity for individual dose adjustment. Presentation: Saturday, June 17, 2023

Developing oral chronotherapy for cortisol replacement in congenital adrenal hyperplasia.

The sun imposes a 24-h periodicity to life and circadian rhythms have evolved to maintain homoeostasis through the day/night cycle. In humans, there is a central clock that controls the sleep/wake cycle which is paralleled metabolically by a fast/feed cycle. The clock maintains homoeostasis by synchronising metabolism to the time of feeding. Loss of synchrony between the clock and hormonal rhythms results in loss of homoeostasis as evidenced by obesity, depression, and diabetes in people undertaking shift work. Cortisol has a distinct circadian rhythm; peaking on waking and low at sleep onset. Loss of this rhythm in adrenal insufficiency is associated with a poor quality of life and increased mortality. To replace the cortisol rhythm requires chronotherapy and for this you need to define the key parameters of the target rhythm, create a formulation to replicate that rhythm, and then prove clinical benefit. The physiology of hormones is more complex than that of nonnative drugs. Hormones are secreted with varied rhythms, bound to multiple cognate binding proteins, and actively transported and cleared through enzymatic pathways in multiple organs. We have examined the diurnal rhythm of cortisol in healthy volunteers, created physiologically-based pharmacokinetic models, and tested various oral delayed and sustained formulations of hydrocortisone (development name, Chronocort) in clinical trials. The outcome from this work was the manufacture of modified-release hydrocortisone hard capsules (tradename Efmody, Diurnal Ltd), that replicate the cortisol diurnal rhythm and improve the disease control of congenital adrenal hyperplasia the commonest hereditary form of adrenal insufficiency.

Modern possibilities and prospects in the treatment of adrenal insufficiency

Adrenal insufficiency (AI) is a life-threatening disease characterized by a decrease in the production of hormones by the adrenal cortex and requires lifelong replacement therapy with glucocorticoids (GCs) and, in some cases, mineralocorticoids (MCs). The number of individuals with primary and secondary AI in Europe is estimated at 20-50 per 100 thousand people, the increase in the number of cases of this disease in the world may be partly due to the rapid increase in the frequency of use of GC in various clinical strategies, including in oncological diseases.In AI, hormone replacement therapy is vital, but long-term use of GC may be associated with various adverse effects, especially at non-physiological concentrations of GC. This review provides a brief overview of the current therapeutic possibilities of AI hormone therapy, which contributes to the prevention of the development of adrenal crises, as well as promising opportunities for more effective imitation of the physiological profile of cortisol, aimed at preventing the development of undesirable effects of therapy. Several different forms of AI are currently available, differing in profile, duration of action, and route of administration. The most preferred currently in the treatment of AI are GCs with a short half-life, which provides a more manageable action profile and a lower risk of side effects. Promising substitution therapy options include modified-release hydrocortisone preparations, as well as new methods of drug administration using an insulin pump, which will better mimic the physiological effects of endogenous cortisol.

Switching patients with Congenital Adrenal Hyperplasia to Modified release hydrocortisone capsules: relative bioavailability and disease control

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Effects of the therapy shift from cortisone acetate to modified-release hydrocortisone in a group of patients with adrenal insufficiency.

Patients with adrenal insufficiency (AI) may be exposed to supraphysiological glucocorticoids levels during standard treatment with cortisone acetate (CA) or immediate-release hydrocortisone (IR-HC). Recent studies, predominantly including patients in IR-HC treatment, suggested that modified-release hydrocortisone (MRH) provide a more physiological cortisol rhythm, improving metabolic control and quality of life. Our primary aim was to assess clinical and biochemical modifications in patients shifted from CA to MRH. We designed a retrospective longitudinal study, enrolling 45 AI patients (22 primary and 23 secondary AI) treated exclusively with CA thrice daily, shifted to MRH once daily; 29/45 patients concluded at least 18-months follow-up (MRH-group). We recruited 35 AI patients continuing CA as a control group (CA-group). Biochemical and clinical data, including metabolic parameters, bone quality, and symptoms of under- or overtreatment were collected. In 24 patients, a daily salivary cortisol curve (SCC) performed before and one month after shifting to MRH was compared to healthy subjects (HS). No significant changes in glycometabolic and bone parameters were observed both in MRH and CA-groups during a median follow-up of 35 months. A more frequent decrease in blood pressure values (23.1% vs 2.8%, p=0.04) and improvement of under- or overtreatment symptoms were observed in MRH vs CA-group. The SCC showed a significant steroid overexposure in both CA and MRH-groups compared to HS [AUC (area under the curve) = 74.4 ± 38.1 nmol×hr/L and 94.6 ± 62.5 nmol×hr/L respectively, vs 44.1 ± 8.4 nmol×hr/L, p<0.01 for both comparisons], although SCC profile was more similar to HS in MRH-group. In our experience, patients shifted from CA to equivalent doses of MRH do not show significant glycometabolic modifications but blood pressure control and symptoms of over-or undertreatment may improve. The lack of amelioration in glucose metabolism and total cortisol daily exposure could suggest the need for a dose reduction when shifting from CA to MRH, due to their different pharmacokinetics.

Modified-release hydrocortisone is associated with lower plasma renin activity in patients with salt-wasting congenital adrenal hyperplasia.

Poorly controlled salt-wasting (SW) congenital adrenal hyperplasia (CAH) patients often require high 9α-fluorocortisol doses as they show high levels of 17-hydroxyprogesterone (17OHP), which is a mineralocorticoid (MC)-receptor antagonist. We investigated the renin-angiotensin-aldosterone system in patients with SW-CAH receiving twice daily modified-release hydrocortisone (MR-HC, Efmody) compared with standard glucocorticoid (GC) therapy. Data were analyzed from the 6-month, phase 3 study of MR-HC (n = 42) versus standard GC therapy (n = 41). MC replacement therapy remained unchanged throughout the study. Blood pressure, serum potassium, serum sodium, plasma renin activity (PRA), and serum 17OHP and androstenedione concentrations were analyzed at baseline, 4, 12, and 24 weeks. The median serum 17OHP in the morning was significantly lower on MR-HC compared with standard GC at 24 weeks (2.5 nmol L-1 (IQR 8.3) versus 10.5 nmol L-1 (IQR 55.2), P = .001). PRA decreased significantly from baseline to 24 weeks in patients on MR-HC (0.83 ng L-1 s-1 (IQR 1.0) to 0.48 ng L-1 s-1 (IQR 0.61), P = .012) but not in patients on standard GC (0.53 ng L-1 s-1 (IQR 0.66) to 0.52 ng L-1 s-1 (IQR 0.78), P = .613). Serum sodium concentrations increased from baseline to 24 weeks in patients on MR-HC (138.8 ± 1.9 mmol L-1 to 139.3 ± 1.8 mmol L-1, P = .047), but remained unchanged on standard GC (139.8 ± 1.6 mmol L-1 to 139.3 ± 1.9 mmol L-1, P = .135). No significant changes were seen in systolic and diastolic blood pressure and serum potassium levels. 6 months of MR-HC therapy decreased PRA and increased sodium levels indicating a greater agonist action of the 9α-fluorocortisol dose, which may be due to the decreased levels of the MC-receptor antagonist 17OHP.

RF09 | PSAT70 Comparison of Prednisolone Versus Modified-release Hydrocortisone (Efmody) in the Treatment of Congenital Adrenal Hyperplasia (CAH)

Abstract Background Prednisolone and prednisone have a longer plasma elimination half-life after oral administration than hydrocortisone: 2.1 to 3.5 vs ∼1.5hrs1,2. For this reason, prednis(ol)one has been used in Congenital Adrenal Hyperplasia (CAH) by giving a dose in the evening to try to prevent the overnight rise in adrenal androgens. Modified-release hydrocortisone (MRHC) capsules, (Efmody, Diurnal Ltd, Cardiff UK), replicate the cortisol diurnal rhythm and improve the control of CAH compared to standard glucocorticoid therapy3. This post-hoc sub-analysis examines CAH control in MRHC treated patients switched from prednis(ol)one. Methods We reviewed the data of all patients taking prednis(ol)one in the randomised study of standard treatment versus MRHC3: 39 classic CAH patients on prednis(ol)one (alone or combined with hydrocortisone) (36 prednisolone; 3 prednisone) were randomised either to continue prednis(ol)one or switched to MRHC at the same hydrocortisone dose equivalent (HDE=prednisolone dose x5). Patients were assessed after 4 weeks following which blinded dose titration according to 17OHP and A4 control was performed to bring 17OHP into the optimal range (&amp;lt;36 nmol/l) and A4 into the reference range. After 24 weeks, 31 patients from the prednis(ol)one prior therapy group participated in an ongoing MHRC single arm extension study with 28 patients completing 18 months follow up. Control of CAH was defined as a 0900h 17OHP &amp;lt;36 nmol/l. Results Median baseline dose (HDE) was 30mg (n=39), androgen control was 56%. In patients randomised to MRHC (n=18), 39% were controlled at baseline and 94% at 4 weeks without dose adjustment. At 24 weeks, after androgen-control guided titration, the HDE dose in the prednis(ol)one group was 34mg, and in the MRHC group 27.5mg, with control being 71% and 94%, respectively. Percentage inhibition of 9am 17OHP from the levels at baseline to that at 24 weeks in the prednis(ol)one group was 32% and in the MRHC group 91%. In this study period there were no adrenal crises in the MRHC group and one in the prednis(ol)one group. MRHC-treated patients in the extension study were further titrated according to clinician assessment, at interim analysis the median MRHC dose was 20mg (median reduction 10mg) and 82% of patients were controlled at 18 months (n=28). In the ongoing extension study of all patients on MRHC (221 patient years), there were 12 adrenal crises in 5 patients (5.4/100 patient years). Conclusions Control of CAH is better on MRHC than prednisolone: 94% vs 39%; and the dose of MRHC can be down titrated to an adrenal replacement dose whilst maintaining control in the majority (82%) of patients.

PSAT087 A de Novo Model for Measuring Long-Term Health Effects of Modified-Release Hydrocortisone Capsules in Adult and Adolescent Patients With Classic Congenital Adrenal Hyperplasia

Abstract Objectives Classic congenital adrenal hyperplasia (C-CAH) is a rare condition caused by enzyme deficiency in cortisol biosynthesis. The condition is characterised by adrenal insufficiency and androgen excess and is associated with numerous disease- and treatment-related comorbidities that impact the length and quality of a patient's life. A de novo model was developed to investigate the long-term health effects of modified-release hydrocortisone capsules (Efmody® / MR-HC) compared to the standard glucocorticoid replacement therapies (including immediate-release hydrocortisone, dexamethasone, and prednisolone) currently used to treat patients with C-CAH. Methods The model is structured as a series of sub-models reflecting key comorbidities in C-CAH: adrenal crisis, cardiovascular disease, bone health, height (adolescents only), obesity, diabetes and infertility. Effects of both disease, i.e. where cortisol and/or androgen levels are too high or low, and the impact of treatment, i.e. physiological or supraphysiological steroid dosing, on each comorbidity are considered where relevant. The model captures accumulating health outcomes from each sub-model and allows quantification of overall impact on health-related quality of life (HRQoL) and mortality. The population is adolescent (&amp;gt;12 years onwards) and adult patients with C-CAH. The intervention is MR-HC, and comparator is standard glucocorticoid replacement therapies currently used in C-CAH. Model inputs, which were composed of MR-HC clinical trial data, published literature values, and clinical opinion, and the modelling approach were validated with seven European clinical experts. The model accumulates the health effect, which is measured as life-years (LYs) and quality-adjusted life years (QALYs), over a lifetime time horizon, from the ages of 12 to 100 years old. Results The model demonstrates that the treatment of C-CAH with standard glucocorticoid replacement therapies known to provide poor hormonal disease control and exposure to supraphysiological steroid dosing long-term have a substantial negative impact on HRQoL and life-expectancy in C-CAH, with modelled outcomes lower than those published for general population. Improved hormonal disease control and physiological steroid dosing with MR-HC compared to standard glucocorticoid replacement therapies result in improvements across the key comorbidities in patients with C-CAH. Quality-adjusted life year (QALY) gains are particularly driven by the reduction in adrenal crises, along with improved growth in the adolescent population and better weight control. Overall, the model demonstrates that long-term treatment of patients with C-CAH with MR-HC, compared to standard glucocorticoid replacement therapies, is expected to extend life by 7.58 years, and results in an additional 3.21 QALYs. Conclusion The model demonstrates that better hormonal disease control without exposing patients to supraphysiological steroid dosing with MR-HC improves key comorbidities in C-CAH resulting in improvement in both the length and the quality of life of patients with C-CAH. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

Comparison of prednisolone and modified-release hydrocortisone capsules in the treatment of congenital adrenal hyperplasia: dose and disease control

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Chronotherapy based on modified-release hydrocortisone to restore the physiological cortisol diurnal rhythm

In this inspirational note, we describe the development of an endocrine chronotherapy to restore the physiological rhythm of the essential adrenal stress hormone, cortisol. The challenges included demonstrating the circadian rhythm of the drug target, creating a drug formulation that replicated that rhythm and then proving benefit in clinical trials. The physiological cortisol circadian rhythm is well defined with cortisol levels high on waking and low on going to sleep. We experimented with different formulation technologies including modified-release tablets and multi-particulates to replicate the cortisol rhythm where absent through disease. We describe the development of Efmody®, a modified-release formulation of hydrocortisone, which replicates the cortisol diurnal rhythm and improves the disease control of congenital adrenal hyperplasia, the commonest hereditary form of adrenal insufficiency. This program shows it is possible, through modified-release technology, to treat chronic endocrine diseases with physiological replacement to preserve health for life.