Long-term safety of once-daily, dual-release hydrocortisone in patients with adrenal insufficiency: a phase 3b, open-label, extension study

Abstract

ObjectiveTo 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).DesignProspective, open-label, multicenter, 5-year extension study of DR-HC conducted at five university clinics in Sweden.MethodsSeventy-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.ResultsTotal 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).ConclusionsIn 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.

Improved insulin sensitivity and secretion in prediabetic patients with adrenal insufficiency on dual‐release hydrocortisone treatment: a 36‐month retrospective analysis

“…By contrast, in a Swedish 5‐year study on 71 patients with PAI treated with DR‐HC, an increase in fasting glucose and HDL‐C was observed, without any change in anthropometric parameters.…”

Improved salivary cortisol rhythm with dual-release hydrocortisone

“…None of the GC therapies previously used (HC or CA) were able to mimic perfectly the physiological cortisol circadian rhythm ( 7 ), exposing to under- as well as over-treatment ( 7 , 8 , 9 , 13 ). Recently, DR-HC has been proposed to patients with AI: its new GC formulation revealed encouraging results in terms of properly mimicking the circadian cortisol profile, closer to normal subjects, reporting a reduction in total daily cortisol exposure, thus leading to an improvement in metabolic and immune parameters ( 10 , 11 , 12 , 23 , 24 ). We proposed to use salivary cortisol to evaluate the cortisol profile in outpatients with AI, since it is a non-invasive and simple tool to assess the adequacy of GC treatment ( 13 , 14 ).…”

An Update on Addison’s Disease

“…In order to improve the pharmacokinetic properties and to better provide circadian cortisol concentrations with a morning peak, a dual-release preparation of hydrocortisone that needs to be given as a single oral dose in the morning has been developed [65]. Early clinical data are promising with regard to drug efficacy and safety [66]. In addition to more patient satisfaction due to the single-dose application, favourable effects with regard to body weight, blood pressure and glycaemic control have been described as compared to standard therapy [67,68].…”