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Endocrine Abstracts (2016) 41 GP14 | DOI: 10.1530/endoabs.41.GP14

ECE2016 Guided Posters Adrenal (1) (10 abstracts)

A Phase 3b, open-label, extension study to evaluate the long-term safety of once-daily, dual-release hydrocortisone (DR-HC) in patients with adrenal insufficiency (AI)

Anna Nilsson 1 , Ragnhildur Bergthorsdottir 1 , Pia Burman 2 , Per Dahlqvist 3 , Bertil Ekman 4 , Britt Edén Engström 5 , Oskar Ragnarsson 1 , Stanko Skrtic 1, , Jeanette Wahlberg 4 , Heinrich Achenbach 7 , Sharif Uddin 8 , Claudio Marelli 7 & Gudmundur Johannsson 1

1Department of Endocrinology, Sahlgrenska University Hospital and Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; 2Department of Endocrinology, Skåne University Hospital Malmö, University of Lund, Malmö, Sweden; 3Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden; 4Department of Endocrinology and Department of Medical and Health Sciences, Linköping University, Linköping, Sweden; 5Department of Medical Sciences, Endocrinology and Mineral Metabolism, University Hospital, Uppsala, Sweden; 6AstraZeneca R&D, Mölndal, Sweden; 7Shire International GmbH, Zug, Switzerland; 8Shire, Lexington, Massachusetts, USA.

Introduction: Glucocorticoid replacement for adrenal insufficiency (AI) remains inadequate, resulting in high morbidity, premature mortality and quality-of-life (QoL) impairment. This study investigated the long-term safety of dual-release hydrocortisone (DR-HC) in patients with primary AI.

Methods: AI patients who completed a randomized, 3-month crossover study of once-daily DR-HC versus thrice-daily conventional immediate-release hydrocortisone plus a 6-month extension of DR-HC (Study 1; n=55) or who were newly recruited (n=16) were included in an open-label, 5-year study of DR-HC (Study 2). Outcomes included safety, intercurrent illness episodes and QoL. Study 2 results are presented for baseline (start of Study 2) to 5 years.

Results: In Study 1, DR-HC was well tolerated and improved metabolic factors, blood pressure and QoL [Johannsson et al. J Clin Endocrin Metab 2012;97:473−81]. In Study 2, 88.7% of patients completed the 5-year visit. Seventy patients (98.6%) reported 1060 adverse events (AEs), of which 84.8% were unrelated to DR-HC. Of 65 serious AEs reported by 32 patients (45.1%), four were possibly related to DR-HC: acute AI (n=2), gastritis (n=1), syncope (n=1). Two deaths were reported (fall from height, subarachnoid haemorrhage), both unrelated to DR-HC. For each 12-month period of the 5-year study, mean number of intercurrent illness episodes per patient varied from 2.64 to 5.42 and mean hydrocortisone dose per episode varied from 18.7 to 23.5 mg. Mean fasting plasma glucose (0.7 mmol/l; P<0.0001) and HDL-cholesterol (0.2 mmol/l; P<0.0001) increased. Patient-assessed DR-HC tolerability was better in 29.5% of patients, equal in 60.7% and worse in 9.8% at 5 years versus baseline (P=0.02). There were no significant changes in Fatigue Impact Scale (FIS) or Psychological General Well Being total scores, but FIS physical functioning worsened (P=0.008).

Conclusions: Long-term DR-HC therapy for AI patients was well tolerated with no safety concerns. Intercurrent illness episodes were stable, and fasting glucose and HDL-cholesterol increased during 5 years’ treatment.

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