Effect of Calcipotriene Plus Betamethasone Dipropionate Topical Suspension on the Hypothalamic-Pituitary-Adrenal Axis and Calcium Homeostasis in Subjects With Extensive Psoriasis Vulgaris: An Open, Non-Controlled, 8-week Trial
August 2013 | Volume 12 | Issue 8 | Original Article | 882 | Copyright © August 2013
Shane Silver MD,a Raj Tuppal MD,b Aditya K Gupta MD,c Fabrice Clonier MSc,d
Martin Olesen MD,e Randy Leeder PhD,e and Victoria Taraska MDf
aDermadvances Research, Winnipeg, MB, Canada
bOshawa Clinic, Oshawa, ON, Canada
cDermsearch/ Mediprobe Research, London ON, Canada
dBiometrics Department, LEO Pharma A/S, Ballerup, Denmark
eMedical Department, LEO Pharma A/S, Ballerup, Denmark
fWinnipeg Clinic, Winnipeg, MB, Canada
OBJECTIVE: To evaluate the systemic effects of once-daily use of two-compound topical suspension/gel on the hypothalamic-pituitary-adrenal (HPA) axis and calcium homeostasis in subjects with extensive psoriasis vulgaris.
METHODS: An open-label, single-group, 8-week trial in 43 subjects with extensive psoriasis covering 15–30% of the body surface area. Blood and 24-hour urine samples were collected and a standard-dose adrenocorticotropic hormone (ACTH) stimulation test was performed at baseline, weeks 4 and 8. Primary endpoints were serum cortisol 30 minutes after ACTH injection (HPA axis response abnormal at serum cortisol ≤18 μg/dL) and changes from baseline in albumin-corrected serum calcium (sCa), 24-hour urinary calcium excretion (24hCa) and urine calcium:creatinine ratio (Ca:Crea).
RESULTS: Two (4.7%) subjects showed signs of adrenal suppression based on the ACTH stimulation test results at week 4; both were withdrawn from treatment and had normal serum cortisol 30-minute values at follow-up 4 weeks later. None of the subjects who continued treatment to week 8 showed signs of adrenal suppression. There were no clinically relevant mean changes from baseline to weeks 4 and 8 in sCa, 24hCa or Ca:Crea and no subject had sCa above the reference range.
CONCLUSION: The two-compound topical suspension/gel containing calcipotriene plus betamethasone dipropionate may be applied once daily to extensive psoriasis vulgaris without generally causing adrenal suppression or disturbance of calcium homeostasis, consistent with previous findings. In a small number of patients with extensive psoriasis treated with large volumes of topical suspension, adrenal suppression may be observed. In the real-world setting, it is anticipated that systemic side-effects would occur in only a few cases within the general psoriasis patient population.
J Drugs Dermatol. 2013;12(8):882-887.
ClinicalTrials.gov Identifier: NCT 01229098