Replace: a randomized controlled trial on the effect of hydrocortisone or placebo in patients with reported symptoms of glucocorticoid-induced adrenal insufficiency after terminating prednisolone for polymyalgia rheumatic/giant cell arteritis

Dreyer Anja Fenger; Borresen Stina Willemoes; Hansen Simon Boggild; Hajir Al-Jorani; Bislev Lise Sofie; Boesen Victor Brun; Christensen Louise Lehmann; Dorte Glintborg; Jensen Richard Christian; Jorgensen Nanna Thurmann; Marianne Klose; Lund Marie Louise; Jelena Stankovic; Randi Tei; Ulla Feldt-Rasmussen; Jorgensen Jens Otto; Marianne Andersen

doi:10.1530/endoabs.99.P126

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Endocrine Abstracts (2024) 99 P126 | DOI: 10.1530/endoabs.99.P126

ECE2024 Poster Presentations Pituitary and Neuroendocrinology (120 abstracts)

Replace: a randomized controlled trial on the effect of hydrocortisone or placebo in patients with reported symptoms of glucocorticoid-induced adrenal insufficiency after terminating prednisolone for polymyalgia rheumatic/giant cell arteritis

Anja Fenger Dreyer ^1,2 , Stina Willemoes Borresen ^3,4 , Simon Bøggild Hansen ^5,6 , Hajir Al-Jorani ^1,2 , Lise Sofie Bislev ^5,6 , Victor Brun Boesen ^3,4 , Louise Lehmann Christensen ^1,2 , Dorte Glintborg ^1,2 , Richard Christian Jensen ¹ , Nanna Thurmann Jørgensen ^3,4 , Marianne Klose ^3,4 , Marie Louise Lund ^3,4 , Jelena Stankovic ^5,6 , Randi Tei ^5,6 , Ulla Feldt-Rasmussen ^3,4 , Jens Otto Jørgensen ^5,6 & Marianne Andersen ^1,2

Err

Author affiliations

¹Odense University Hospital, Department of Endocrinology, Odense C, Denmark; ²University of Southern Denmark, Department of Clinical Research, Faculty of Health Sciences, Odense C, Denmark; ³Copenhagen University Hospital, Department of Endocrinology and Metabolism, Rigshospitalet, Copenhagen, Denmark; ⁴Copenhagen University, Department of Clinical Medicine, Faculty of Health and Clinical Sciences, Copenhagen, Denmark; ⁵Aarhus University Hospital, Department of Endocrinology and Internal Medicine, Aarhus, Denmark; ⁶Aarhus University, Department of Clinical Medicine, Aarhus, Denmark

Background: Glucocorticoid-induced adrenal insufficiency (GIA) may occur after termination of long-term glucocorticoid (GC) treatment. GIA is usually diagnosed by a short-synacthen-test (SST), but peak cortisol response to SST may not validly assess normalisation of the diurnal hypothalamic-pituitary-adrenal (HPA)-axis. In patients with polymyalgia rheumatic (PMR) and giant cell arteritis (GCA), we report at this meeting a surprisingly low prevalence of GIA of 1.6% after cessation of prednisolone treatment; whereas 33% of these patients reported symptoms of GIA (scores ≤85) according to the Addison’s disease-specific quality-of-life questionnaire (AddiQoL-30) (ECE 2024 abstract ID: 5059). The primary study aim is to generate evidence-based guidance for management of GIA in patients using patient reported outcomes as a key tool for inclusion and outcome.

Methods: This is the first RCT to randomize patients with low AddiQoL-30 score after long-term GC use to hydrocortisone treatment or placebo. The REPLACE study is a multi-centre randomised, double-blinded, placebo-controlled study. Eligible patients have PMR and/or GCA and are in GC free remission for 2-12 weeks after long-term prednisolone treatment (>12 weeks). Patients are assigned to one of the study groups according to results of AddiQoL-30 and SST: All groups will participate in a standardized baseline visit. The RCT-group is randomized to either hydrocortisone or placebo for 16 weeks with repetition of baseline investigations at end of study.


RCT-group	AddiQoL-score ≤85 or 30 min. cortisol level >100 nmol/l and <420 nmol/l n=100
Control-group 1	AddiQoL-score >85 and 30 min. cortisol level ≥420 nmol/l n=150
Control-group 2	30 min. cortisol level ≤100 nmol/l regardless of AddiQoL-score n=20

Outcomes: Change in GIA symptom burden (AddiQoL-30) at 16-week follow-up is the primary outcome. Secondary outcomes are generic health-related QoL questionnaire scores (CushingQoL, SF-36v2, Single item Sleep Quality Scale, and the International Physical Activity Questionnaire-S7S). Participants will daily report on intercurrent illness and stress, and symptoms attributable to GIA, using a study smartphone application (app). Baseline and follow-up investigations of cardiovascular health, body composition, muscle function, and glucose homeostasis will be completed.

Ethics and dissemination: The REPLACE study is in accordance with the Declaration of Helsinki; registered at EudraCT (2020-006121-65) and publications will be according to the International Committee of Medical Journal Editors recommendations.

Funding: The REPLACE study is funded by the Novo Nordisk Foundation as part of a collaborative grant entitled ‘DOUBLE EDGE – Characterization and mitigation of adverse effects of glucocorticoid treatment’ (NNF20OC0063280).

Status: Recruiting.