TY - JOUR
T1 - Prospective evaluation of long-term safety of dual-release hydrocortisone replacement administered once daily in patients with adrenal insufficiency.
AU - Nilsson, Anna G
AU - Marelli, Claudio
AU - Fitts, David
AU - Bergthorsdottir, Ragnhildur
AU - Burman, Pia
AU - Dahlqvist, Per
AU - Ekman, Bertil
AU - Edén Engström, Britt
AU - Olsson, Tommy
AU - Ragnarsson, Oskar
AU - Ryberg, Mats
AU - Wahlberg, Jeanette
AU - Lennernas, Hans
AU - Skrtic, Stanko
AU - Johannsson, Gudmundur
PY - 2014
Y1 - 2014
N2 - Objective: The objective was to assess the long-term safety profile of dual-release hydrocortisone (DR-HC) in patients with adrenal insufficiency. Design: Randomized, open-label, crossover trial of DR-HC or thrice-daily hydrocortisone for 3 months each (stage 1) followed by two consecutive, prospective, open-label studies of DR-HC for 6 months (stage 2) and 18 months (stage 3) at five university clinics in Sweden. Methods: Sixty-four adults with primary AI started stage 1 and an additional 16 entered stage 3. Patients received DR-HC 20-40 mg once daily and hydrocortisone 20-40 mg divided into three daily doses (stage 1 only). Main outcome measures were adverse events (AEs) and intercurrent illness (self-reported hydrocortisone use during illness). Results: In stage 1, patients had a median 1.5 (range 1-9) intercurrent illness events with DR-HC and 1.0 (1-8) with thrice-daily hydrocortisone. AEs during stage 1 were not related to the cortisol exposure-time profile. The percentage of patients with one or more AEs during stage 1 (73.4% with DR-HC; 65.6% with thrice-daily hydrocortisone) decreased during stage 2, when all patients received DR-HC (51% in the first 3 months; 54% in the second 3 months). In stages 1-3 combined, 19 patients experienced 27 serious AEs, equating to 18.6 serious AEs/100 patient-years of DR-HC exposure. Conclusions: This long-term prospective trial is the first to document the safety of DR-HC in patients with primary AI, and has demonstrated that such treatment is well tolerated during 24 consecutive months of therapy.
AB - Objective: The objective was to assess the long-term safety profile of dual-release hydrocortisone (DR-HC) in patients with adrenal insufficiency. Design: Randomized, open-label, crossover trial of DR-HC or thrice-daily hydrocortisone for 3 months each (stage 1) followed by two consecutive, prospective, open-label studies of DR-HC for 6 months (stage 2) and 18 months (stage 3) at five university clinics in Sweden. Methods: Sixty-four adults with primary AI started stage 1 and an additional 16 entered stage 3. Patients received DR-HC 20-40 mg once daily and hydrocortisone 20-40 mg divided into three daily doses (stage 1 only). Main outcome measures were adverse events (AEs) and intercurrent illness (self-reported hydrocortisone use during illness). Results: In stage 1, patients had a median 1.5 (range 1-9) intercurrent illness events with DR-HC and 1.0 (1-8) with thrice-daily hydrocortisone. AEs during stage 1 were not related to the cortisol exposure-time profile. The percentage of patients with one or more AEs during stage 1 (73.4% with DR-HC; 65.6% with thrice-daily hydrocortisone) decreased during stage 2, when all patients received DR-HC (51% in the first 3 months; 54% in the second 3 months). In stages 1-3 combined, 19 patients experienced 27 serious AEs, equating to 18.6 serious AEs/100 patient-years of DR-HC exposure. Conclusions: This long-term prospective trial is the first to document the safety of DR-HC in patients with primary AI, and has demonstrated that such treatment is well tolerated during 24 consecutive months of therapy.
U2 - 10.1530/EJE-14-0327
DO - 10.1530/EJE-14-0327
M3 - Article
C2 - 24944332
SN - 1479-683X
VL - 171
SP - 369
EP - 377
JO - European Journal of Endocrinology
JF - European Journal of Endocrinology
IS - 3
ER -
