Short-term safety assessment of clobetasol propionate 0.05% shampoo: hypothalamic-pituitary-adrenal axis suppression, atrophogenicity, and ocular safety in subjects with scalp psoriasis

Journal of Drugs in Dermatology, April, 2006 by Philippe Andres, Michel Poncet, Farzaneh Sidou, Pascale Soto

Abstract

Clobetasol propionate is known to be a very effective treatment for psoriasis; however, its use is limited by potent corticosteroid class related side effects such as hypothalamic-pituitary-adrenal (HPA) axis suppression and atrophogenicity. The aim of this single-center, parallel group, randomized study was to assess the HPA axis suppression potential, atrophogenicity, and ocular tolerability of clobetasol propionate shampoo in 26 patients with scalp psoriasis. Suitable subjects were treated once daily for 4 weeks with clobetasol propionate shampoo, to be rinsed off after 15 minutes or with a leave-on clobetasol propionate gel.

The study demonstrated that clobetasol propionate shampoo did not lead to HPA axis suppression or to skin atrophy. Conversely, the gel led to HPA axis suppression and a decrease in skin thickness. Neither formulation had an impact on ocular safety. Despite the short contact application time, the clobetasol propionate shampoo provides similar efficacy results to the gel.

Introduction

The efficacy of topical, very strong (or super-potent) corticosteroids, such as clobetasol propionate, is well established. (1-3) However, their good efficacy profile is tempered by safety issues such as hypothalamic-pituitary-adrenal (HPA) axis suppression, skin thinning, iatrogenic Cushing's syndrome, and glaucoma (rise of the intraocular pressure). (1,4-12) Throughout various clinical studies it could be demonstrated that the risk of a clinically significant HPA axis suppression increases with duration of use; very strong topical corticosteroids are therefore only recommended for short treatment periods. (1,5-11)

Other studies have demonstrated the occurrence of skin atrophy after the topical administration of very strong corticosteroids, including clobetasol propionate. (13-17) However, all these studies were performed either in healthy volunteers or on psoriasis areas other than the scalp. To our knowledge, no clinical study has been conducted so far to investigate the impact on skin atrophy of clobetasol propionate applied locally to the scalp.

Various publications report that corticosteroids, when in contact with the eyes, may induce irritation and cataracts as well as glaucoma. (18-21) As the risk of contact with the eyes during application or rinsing of clobetasol propionate shampoo can not be excluded, ocular safety is certainly to be taken into consideration.

The present clinical study was conducted to assess the impact of clobetasol propionate shampoo (Clobex Shampoo[R], Galderma Laboratories L.P., Ft Worth, Texas, USA) on the HPA axis function, the potential for skin thinning and the ocular safety compared to a currently available gel formulation (Dermoval[R]/Temovate[R] gel, 0.05% Glaxo Welcome, France), both indicated for the treatment of scalp psoriasis.

Methods

The present study received approval by the local ethics committee before subject enrollment, and was conducted in accordance with the Declaration of Helsinki and its amendments. All subjects gave written informed consent before entering the study.

Study Design and Population

The study had a single center, parallel-group, randomized design, using an active comparator. The study period was 4 weeks; evaluations took place at baseline, Week 2, and Week 4. To be included in the study, subjects had to have scalp psoriasis involving at least 25% of the scalp surface and a dermatological sum score (DSS, see below) of at least 3. Subjects taking or applying topical or systemic treatments likely to interfere with either psoriasis status or HPA axis function were required to undergo specific wash-out periods. Women were excluded if they were pregnant or breastfeeding, or at risk of pregnancy. Individuals suffering from ophthalmological disorders or wearing contact lenses were not suitable for this study.

Treatments

Subjects received either clobetasol propionate 0.05% shampoo or clobetasol propionate 0.05% gel in accordance with a computer generated randomization list. Investigators did not know the treatment provided to the subjects. However, due to the different formulations and ways of administration, it was not possible to mask the identity of the treatment from the subjects.

For all subjects, the planned length of treatment was 4 weeks. Subjects assigned to clobetasol propionate gel were instructed to apply the product once-daily to a dry scalp. Individuals assigned to clobetasol propionate shampoo were instructed to apply the product once daily to a dry scalp, and then rinse off after 15 minutes.

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Safety and Efficacy Assessments

During the course of the study, serum cortisol measurements, atrophogenicity, ocular safety, as well as efficacy of clobetasol propionate were evaluated.

All cortisol measurements had to be conducted between 7:30 am and 8:30 am, prior to receiving the applied dose of study medication for that study day. To avoid intra-subject variations for serum cortisol levels as much as possible, only a half an hour gap from the previous visit time was authorized at each visit. After collecting the pre-stimulation serum cortisol sample, subjects were given an intravenous injection of 0.25 mg cosyntropin (Synacthene[R], Novartis Pharma, France), and a further blood sample was taken 60 minutes later for measurement of stimulated serum cortisol. Cortisol measurements were conducted with Mini-Vidas analyzer (Bio-Meriuex, France) using the ELFA (Enzyme Linked Fluorescent Assay) technique.