Clobetasol propionate 0.05% lotion in the treatment of moderate to severe atopic dermatitis: a randomized evaluation versus clobetasol propionate emollient cream

Journal of Drugs in Dermatology, May-June, 2005 by Debra Breneman, Alan B. Fleischer, Jr., David Kaplan, Mark Lebwohl, Bruce Miller, David Pariser, Toivo Rist, L. Swinyer, Yin Liu, Valerie Foley

Abstract

Atopic dermatitis (AD) is a chronic inflammatory and pruritic skin disorder marked by alternating periods of relapse and remission. This multicenter, randomized, active- and vehicle-controlled, investigator-blinded study compared the efficacy and safety of clobetasol propionate lotion to clobetasol propionate cream formulation and lotion vehicle in the treatment of moderate to severe AD. A total of 229 subjects applied treatment twice-daily for 2 weeks. Clobetasol propionate lotion was significantly more effective than its lotion vehicle at 2 weeks and comparable to the cream formulation. Clinical success after a 2-week, treatment-free follow-up period was greater in the clobetasol propionate lotion group than in the cream group. Clobetasol propionate lotion is effective, safe, well tolerated and offers a better remission profile in the treatment of moderate to severe AD as compared to clobetasol propionate emollient cream.

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Introduction

Atopic dermatitis (AD) is a common inflammatory and pruritic skin disorder that often presents in early childhood, may continue into later life, and usually appears in a personal or family history of atopy. (1-4) AD is a chronic disease marked by alternating periods of exacerbations and remissions with up to 20% of school-aged children being affected by AD, potentially profoundly influencing their quality of life. (5,6)

Due to their potency in inflammatory skin disease, topical corticosteroids are the mainstay of treatment for various dermatoses, and are among the most frequently used dermatologicals. (7,8) An increasing number of preparations of topical corticosteroids have been developed in the past few years focusing on the development of more powerful compounds with improved bioavailability and reduced risk of side effects. (8)

Clobetasol propionate, one of these high-potency topical corticosteroid compounds, has anti-inflammatory, antipruritic, vasoconstrictive, and immune-modulating properties. It is currently used in the treatment of a variety of hyperproliferative and/or inflammatory dermatoses, including psoriasis and AD. (10-12)

Recently, a new lotion formulation of clobetasol propionate 0.05% (Clobex[TM] lotion, Galderma Laoratories L.P. Fort Worth, TX) has been launched to provide a greater breadth of treatment options. The objective of this multicenter, randomized, investigator-blinded, active- and vehicle-controlled, parallel comparison was to demonstrate the efficacy and safety profile of the clobetasol propionate lotion formulation relative to the clobetasol propionate emollient cream formulation and the lotion vehicle in the treatment of moderate to severe AD.

Methods

The study was conducted in accordance with the Declaration of Helsinki and its amendments and with the Guidelines for Good Clinical Practices. IRB approvals for all study sites were obtained before the start of the study and subjects provided written informed consent prior to any study related procedures.

Subjects

A total of 224 male and female subjects with stable moderate to severe AD were enrolled in the study. Individuals had to have a total baseline Dermatological Sum Score (DSS, sum of erythema, excoriation, and induration/papulation) of at least 6 in the target area and at least 3 of the following signs and symptoms: pruritus, flexural lichenification, linearity in adults with a variety of skin lesions, chronic or chronically-relapsing dermatitis, or personal or family history of atopy (asthma, allergic rhinitis, AD). Subjects with concomitant medical or dermatologic disorders precluding accurate evaluation of the AD, or using interfering concomitant therapies or with known sensitivities to any ingredients of the study treatments were not allowed to participate. Specific wash-out periods were to be respected for topical and systemic AD treatments. Topical treatments (excluding sunscreen on the face) other than the test material were not permitted.

Test Material

Each investigator enrolled approximately 10 to 20 subjects. Qualified subjects were randomized into consecutive balanced blocks of 7 to receive clobetasol propionate 0.05% lotion (hereafter named lotion), clobetasol propionate emollient 0.05% cream (hereafter named emollient cream or cream), or the lotion vehicle in a ratio of 3:3:1. Subjects received both verbal and written instructions as to the proper dosing and study medication application techniques.

Since the active products were 2 different formulations, the comparison versus emollient cream was investigator-blinded only. Drugs were dispensed by a third person, independent from the investigator, and subjects were asked not to discuss the external aspects of the study medication with the investigator. Application of test material was made as a thin coating twice-daily for 2 weeks to the designated target lesion, as well as to other affected areas.

Clinical Assessments

Efficacy and safety were assessed at baseline, weeks 1, 2, and 4. The primary efficacy variable was the success rate, which was derived from Global Severity scale dichotomized as "success" or "failure," where success was defined as a Global Severity score of 0, 0.5, or 1 (none to mild) and failure was defined as Global Severity scores of 2, 3, or 4 (moderate to very severe). Secondary efficacy variables for this study were Global Severity (full-scale); DSS, individual disease scores (scale 0 [none] to 4 [severe]) of erythema, excoriation, induration/papulation, lichenification, oozing/crusting, and dryness/scaling; pruritus, global improvement. For variables describing 2 signs or symptoms (ie, induration/papulation), the score that best described the most severe sign or symptom was chosen when the scored signs or symptoms differed. For example, a subject who presented with "mild" induration and "moderate" papulation was scored as moderate induration/papulation. A 2-week follow-up period served to assess the durability of response following treatment discontinuation.