8794 A Switch From Conventional Glucocorticoid To Modified-Release Hydrocortisone Treatment In Patients With Congenital Adrenal Hyperplasia Restores Levels Of Regulatory T Cells
Authors: Nowotny H F , Ziegler S , Choi H , Tschaidse L , Auer M , Gottschlich A , Kobold S , Rothenfusser S , Reisch N 
Published: October 2024

Disclosure: H.F. Nowotny: Advisory Board Member; Self; Novartis Pharmaceuticals. S. Ziegler: None. H. Choi: None. L. Tschaidse: None. M. Auer: None. A. Gottschlich: Other; Self; Tabby Therapeutics. S. Kobold: Consulting Fee; Self; TCR2 Inc, Novartis, BMS, GSK, Plectonic GmbH and Arcus Bioscience. S. Rothenfusser: None. N. Reisch: None.

A switch from conventional glucocorticoid to modified-release hydrocortisone treatment in patients with congenital adrenal hyperplasia restores levels of regulatory T cells. Background: Patients with classic congenital adrenal hyperplasia (CAH) require glucocorticoid replacement (GC) therapy. Conventional glucocorticoids however fail to mimic circadian cortisol release. Modified-release hydrocortisone (MR-HC, Efmody) has been shown to imitate the early morning cortisol surge in CAH. The aim of the study was to investigate potential benefits of MR-HC on the immune phenotype in patients with CAH. Methods: This single centre study included 28 patients with classic CAH (females 16, males 12), with a median age of 35,5 years (IQR 15) and a median BMI of 25,22 kg/m2 (IQR 3,94), who had been switched from conventional hydrocortisone (n =13) or prednisolone (n =15) -regimens in equivalent doses to MR-HC treatment and 28 sex, age, and BMI matched healthy controls. Peripheral blood mononuclear cells were isolated at the beginning of the study, after 3 and 6 to 10 months of MR-HC replacement. Using multicolour flow cytometry, immune cell subsets following a four-hour stimulation with PMI/ionomycin were analysed. Results: We observed a significantly increased proportion of CD4+CD25+ lymphocytes in patients that are treated with conventional GCs (p=0,0033), whereas patients treated with MR-HC show similar proportions compared to the control group. In a direct comparison of data before and after medication change, the percentage in patients treated with conventional GC was higher than after switch to MR-HC treatment (p=0,0485). Strikingly, a lower percentage of CD4+CD25+Foxp3+ regulatory T cells (Tregs) was detected with conventional GC treatment compared to the control group (p=0,0007), while after switch to MR-HC treatment, the percentage of Tregs was similar to those of control subjects. In patients receiving dose reductions due to excellent therapeutic control between the timepoints 3 to 6 months after switch to MR-HC, an increase in the percentage of T helper cells (p=0,0034) and decreasing CD94+ NK cells (p=0,0312) was observed. Conclusion: Our data suggests a profound effect of improved circadian cortisol replacement on the immunophenotype of patients with CAH. By mimicking the early morning cortisol surge, MR-HC seems to partially restore the physiological activity of immune cells. A switch from conventional GC to MR-HC treatment eventually results in reprogramming Tregs towards levels shown by the healthy control cohort potentially improving antiviral or antitumor immunity.

Presentation: 6/1/2024