December 12, 2016
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Glucocorticoid replacement therapy varies widely in real-world practice

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Approximately one in eight European patients with primary or secondary adrenal insufficiency are receiving a higher-than-recommended dose of glucocorticoid replacement therapy, whereas 7% of patients are receiving doses that fall below guideline recommendations, according to a recent database analysis.

“The intention of current treatment regimens is to mimic the normal circadian pattern of endogenous plasma cortisol,” Robert D. Murray, MD, MRCP, of the Leeds Center for Diabetes and Endocrinology at St. James’s University Hospital, United Kingdom, and colleagues wrote. “However, in the absence of a specific biomarker to guide glucocorticoid replacement, treatment is guided by the subjective health status of the individual, alongside clinical assessment of signs and symptoms of glucocorticoid over- or under-replacement. These variables lead to individualization of glucocorticoid replacement regimens. This analysis highlights that a multitude of different regimens, in terms of dosage, frequency, dose regimen and glucocorticoid type, are utilized.”

Murray and colleagues analyzed data from 1,166 adults with primary or secondary adrenal insufficiency participating in the European Adrenal Insufficiency Registry (EU-AIR), a prospective, multinational, observational study initiated in August 2012 to monitor the long-term safety of glucocorticoid replacement therapy in routine clinical practice in Germany, the Netherlands, Sweden and the United Kingdom (mean age, 54 years; 53% women; mean disease duration, 16.1 years). Researchers assessed the glucocorticoid therapy type, dose and frequency in the cohort.

Within the cohort, 31.2% had primary adrenal insufficiency; 68.7% had secondary adrenal insufficiency. Hydrocortisone was the most frequently used glucocorticoid replacement therapy (87.4%), followed by prednisone (5.1%), cortisone acetate (4%) and dexamethasone (0.1%).

The daily dose of therapy varied widely, according to researchers, ranging from 5 mg to 45 mg. The most common dose range was between 20 mg and 25 mg per day (42.2% of patients), followed by doses between 25 mg and 30 mg (15.2% of patients); 12.6% of patients were prescribed at least 30 mg per day.

“A substantial proportion of patients within our cohort appear to be over-replaced, increasing the risk of reduced bone mineral density, cardiovascular disease and an adverse metabolic profile,” the researchers wrote. “At the other end of the spectrum, inadequate glucocorticoid replacement also has important clinical consequences. In this study, 7.2% of patients were receiving hydrocortisone doses of < 15 mg per day.”

Most patients were prescribed hydrocortisone either twice daily (48.7%) or three times daily (43.6%), with patients with primary adrenal insufficiency more likely to be prescribed therapy three times per day vs. those with secondary adrenal insufficiency.

The timing of dosing also varied widely, according to researchers, who identified 25 different dosing regimens used to deliver a daily dose of 20 mg hydrocortisone. The most common regimen was 10 mg administered in the morning, 5 mg at midday and 5 mg in the evening (28.2% of patients), followed by a twice-daily regimen of 10 mg in the morning and 10 mg at midday (18%).

“The majority of these regimens provide a larger dose on waking, followed by one or two smaller doses throughout the day to approximate the physiological cortisol secretion profile,” the researchers wrote. “How glucocorticoid replacement is delivered is of importance, as it can result in non-physiological spikes and troughs in cortisol levels and nighttime cortisol exposure.”

The researchers noted that future data from EU-AIR could help inform best practice in the management of patients with adrenal insufficiency. – by Regina Schaffer

Disclosure: Shire Development LLC funded EU-AIR and supported this study. All researchers report receiving honoraria for talks and consultancy fees from ViroPharma/Shire or are employees of Shire.