| 1. |
- Murray, Robert D., et al.
(författare)
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Management of glucocorticoid replacement in adrenal insufficiency shows notable heterogeneity - data from the EU-AIR
- 2017
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Ingår i: Clinical Endocrinology. - : WILEY. - 0300-0664 .- 1365-2265. ; 86:3, s. 340-346
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Tidskriftsartikel (refereegranskat)abstract
- Context and objectiveTreatment for adrenal insufficiency (AI) remains suboptimal. Despite glucocorticoid replacement, patients with AI have reduced life expectancy and quality of life. This study aimed to describe the spectrum of management of glucocorticoid replacement in patients with AI enrolled in the European Adrenal Insufficiency Registry (EU-AIR). Design, setting and patientsEU-AIR is a prospective, multinational, multicentre, observational study initiated in August 2012 to monitor the long-term safety of glucocorticoid replacement in routine clinical practice in Germany, the Netherlands, Sweden and the UK (ClinicalTrials.gov identifier: NCT01661387). This analysis included 1166 patients with primary and secondary AI (mean disease duration 16amp;lt;boldamp;gt;amp;lt;/boldamp;gt;1 11amp;lt;boldamp;gt;amp;lt;/boldamp;gt;6 years) receiving long-term glucocorticoid replacement therapy. Main outcome measureGlucocorticoid type, dose, frequency and treatment regimen were examined. ResultsMost patients (87amp;lt;boldamp;gt;amp;lt;/boldamp;gt;4%) were receiving hydrocortisone. The most common dose range, taken by 42amp;lt;boldamp;gt;amp;lt;/boldamp;gt;2% of patients, was 20 to amp;lt;25 mg/day; however, 12amp;lt;boldamp;gt;amp;lt;/boldamp;gt;6% were receiving doses of 30 mg/day. Hydrocortisone was being taken once daily by 5amp;lt;boldamp;gt;amp;lt;/boldamp;gt;5%, twice daily by 48amp;lt;boldamp;gt;amp;lt;/boldamp;gt;7%, three times daily by 43amp;lt;boldamp;gt;amp;lt;/boldamp;gt;6% and four times daily by 2amp;lt;boldamp;gt;amp;lt;/boldamp;gt;1%. Patients with primary AI received higher replacement doses than those with secondary AI (23amp;lt;boldamp;gt;amp;lt;/boldamp;gt;4 +/- 8amp;lt;boldamp;gt;amp;lt;/boldamp;gt;9 and 19amp;lt;boldamp;gt;amp;lt;/boldamp;gt;6 +/- 5amp;lt;boldamp;gt;amp;lt;/boldamp;gt;9 mg/day, respectively). Twenty-five different regimens were being used to deliver a daily hydrocortisone dose of 20 mg. ConclusionsWe have shown significant heterogeneity in the type, dose, frequency and timing of glucocorticoid replacement in real-world clinical practice. This reflects dose individualization based on patient symptoms and lifestyle in the absence of data supporting the optimal regimen.
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| 2. |
- Nilsson, Anna G., et al.
(författare)
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Long-term safety of once-daily, dual-release hydrocortisone in patients with adrenal insufficiency : a phase 3b, open-label, extension study
- 2017
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Ingår i: European Journal of Endocrinology. - : Bioscientifica. - 0804-4643 .- 1479-683X. ; 176:6, s. 715-725
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To investigate the long-term safety and tolerability of a once-daily, dual-release hydrocortisone (DR-HC) tablet as oral glucocorticoid replacement therapy in patients with primary adrenal insufficiency (AI).Design: Prospective, open-label, multicenter, 5-year extension study of DR-HC conducted at five university clinics in Sweden.Methods: Seventy-one adult patients diagnosed with primary AI who were receiving stable glucocorticoid replacement therapy were recruited. Safety and tolerability outcomes included adverse events (AEs), intercurrent illness episodes, laboratory parameters and vital signs. Quality of life (QoL) was evaluated using generic questionnaires.Results: Total DR-HC exposure was 328 patient-treatment years. Seventy patients reported 1060 AEs (323 per 100 patient-years); 85% were considered unrelated to DR-HC by the investigator. The most common AEs were nasopharyngitis (70%), fatigue (52%) and gastroenteritis (48%). Of 65 serious AEs reported by 32 patients (20 per 100 patient-years), four were considered to be possibly related to DR-HC: acute AI (n = 2), gastritis (n = 1) and syncope (n = 1). Two deaths were reported (fall from height and subarachnoid hemorrhage), both considered to be unrelated to DR-HC. From baseline to 5 years, intercurrent illness episodes remained relatively stable (mean 2.6-5.4 episodes per patient per year), fasting plasma glucose (0.7 mmol/L; P < 0.0001) and HDL cholesterol (0.2 mmol/L; P < 0.0001) increased and patient-/investigator-assessed tolerability improved. QoL total scores were unchanged but worsening physical functioning was recorded (P = 0.008).Conclusions: In the first prospective study evaluating the long-term safety of glucocorticoid replacement therapy in patients with primary AI, DR-HC was well tolerated with no safety concerns observed during 5-year treatment.
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| 3. |
- Nilsson, Anna G, 1968, et al.
(författare)
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Long-term safety of once-daily, dual-release hydrocortisone in patients with adrenal insufficiency: a phase 3b, open-label, extension study.
- 2017
-
Ingår i: European journal of endocrinology. - : BIOSCIENTIFICA LTD. - 1479-683X .- 0804-4643. ; 176:6, s. 715-725
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Tidskriftsartikel (refereegranskat)abstract
- To investigate the long-term safety and tolerability of a once-daily, dual-release hydrocortisone (DR-HC) tablet as oral glucocorticoid replacement therapy in patients with primary adrenal insufficiency (AI).Prospective, open-label, multicenter, 5-year extension study of DR-HC conducted at five university clinics in Sweden.Seventy-one adult patients diagnosed with primary AI who were receiving stable glucocorticoid replacement therapy were recruited. Safety and tolerability outcomes included adverse events (AEs), intercurrent illness episodes, laboratory parameters and vital signs. Quality of life (QoL) was evaluated using generic questionnaires.Total DR-HC exposure was 328 patient-treatment years. Seventy patients reported 1060 AEs (323 per 100 patient-years); 85% were considered unrelated to DR-HC by the investigator. The most common AEs were nasopharyngitis (70%), fatigue (52%) and gastroenteritis (48%). Of 65 serious AEs reported by 32 patients (20 per 100 patient-years), four were considered to be possibly related to DR-HC: acute AI (n=2), gastritis (n=1) and syncope (n=1). Two deaths were reported (fall from height and subarachnoid hemorrhage), both considered to be unrelated to DR-HC. From baseline to 5 years, intercurrent illness episodes remained relatively stable (mean 2.6-5.4 episodes per patient per year), fasting plasma glucose (0.7mmol/L; P<0.0001) and HDL cholesterol (0.2mmol/L; P<0.0001) increased and patient-/investigator-assessed tolerability improved. QoL total scores were unchanged but worsening physical functioning was recorded (P=0.008).In the first prospective study evaluating the long-term safety of glucocorticoid replacement therapy in patients with primary AI, DR-HC was well tolerated with no safety concerns observed during 5-year treatment.
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| 4. |
- Quinkler, Marcus, et al.
(författare)
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Prednisolone is associated with a worse lipid profile than hydrocortisone in patients with adrenal insufficiency
- 2017
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Ingår i: Endocrine Connections. - : BIOSCIENTIFICA LTD. - 2049-3614. ; 6:1
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Prednisolone is used as glucocorticoid replacement therapy for adrenal insufficiency (AI). Recent data indicate that its use in AI is associated with low bone mineral density. Data on risk factors for cardiovascular disease in patients with AI treated with prednisolone are scarce, despite this condition being the predominant cause of excess mortality. We aimed to address this question using real-world data from the European Adrenal Insufficiency Registry (EU-AIR). Design/methods: EU-AIR, comprising of 19 centres across Germany, the Netherlands, Sweden and the UK, commenced enrolling patients with AI in August 2012. Patients receiving prednisolone (3-6 mg/day, n = 50) or hydrocortisone (15-30 mg/day, n = 909) were identified and grouped at a ratio of 1: 3 (prednisolone: hydrocortisone) by matching for gender, age, duration and type of disease. Data from baseline and follow-up visits were analysed. Data from patients with congenital adrenal hyperplasia were excluded. Results: Significantly higher mean +/- s. d. total (6.3 +/- 1.6 vs 5.4 +/- 1.1 mmol/L; P = 0.003) and low-density lipoprotein (LDL) cholesterol levels (3.9 +/- 1.4 vs 3.2 +/- 1.0 mmol/L; P = 0.013) were identified in 47 patients on prednisolone vs 141 receiving hydrocortisone at baseline and at follow-up (P = 0.005 and P = 0.006, respectively). HbA1c, high-density lipoprotein and triglyceride levels, body mass index, systolic and diastolic blood pressure and waist circumference were not significantly different. Conclusions: This is the first matched analysis of its kind. Significantly higher LDL levels in patients receiving prednisolone relative to hydrocortisone could predict a higher relative risk of cardiovascular disease in the former group.
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