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
Abstract
BACKGROUND: The two-compound topical suspension/gel containing calcipotriene plus betamethasone dipropionate is effective and safe in the treatment of psoriasis on the body and scalp within the general psoriasis patient population.
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Two (4.7%) subjects showed signs of adrenal suppression based on the ACTH stimulation test results at week 4; both were withdrawn from treatment and had normal serum cortisol 30-minute values at follow-up 4 weeks later.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
INTRODUCTION
A two-compound ointment containing 50 μg/g calcipotriene plus 0.5 mg/g betamethasone (as dipropionate) has good efficacy and is a safe treatment for psoriasis vulgaris of the body.1 However, in some patients, ointments are unacceptably greasy and messy to use, resulting in decreased treatment adherence.2 A two-compound, lipophilic and non-alcoholic topical suspension (described as a gel in some countries) containing 50 μg/g calcipotriene plus 0.5 mg/g beta-methasone(as dipropionate) has also been developed, and is effective and safe for treating psoriasis of the body and scalp.1,3
Topical psoriasis treatments are typically used on limited body surface areas. However, in cases of extensive psoriasis, the large volumes of topical treatment required can increase the risk of systemic side effects if sufficient quantities of the active substances are applied and absorbed. The main potential consequences with the two-compound product are effects on calcium homeostasis due to the vitamin D analogue calcipotriene4 and suppression of the hypothalamic-pituitary-adrenal (HPA) axis due to the potent corticosteroid betamethasone dipropionate.5
Adrenal suppression is more likely to occur with the higher potency topical corticosteroids.6 It tends to occur early in the course of treatment and may decrease with continued therapy as the skin heals,7 although prolonged treatment may also increase
