Safety and efficacy of desonide hydrogel 0.05% in pediatric subjects with atopic dermatitis

Journal of Drugs in Dermatology,  Feb, 2007  by Adelaide A. Hebert,  Fran E. Cook-Bolden,  Sarmistha Basu,  Barry Calvarese,  Ronald J. Trancik

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Abstract

Low to mid potency corticosteroids remain a cornerstone of therapy for atopic dermatitis (AD). Since AD is most prevalent in the younger pediatric population and is chronic in nature, safety is of particular concern especially for children under 2 years of age. A novel desonide (0.05%) formulation was developed in a nonirritating and moisturizing aqueous gel (hydrogel) that is free of alcohol and surfactants. The safety and efficacy of this new class VI low potency topical steroid was substantiated in 2 phase III clinical trials in mild to moderate AD subjects aged 3 months to 18 years (mean age 6.7 years and 30% under 3 years). A total of 425 subjects were treated with desonide hydrogel and 157 subjects with the hydrogel vehicle. Desonide hydrogel 0.05% was extremely well-tolerated and provided statistically significant improvements in all primary (P<.001) and secondary (P[less than or equal to].006) efficacy endpoints in both studies. This novel desonide formulation represents an advancement in the treatment of AD.

Introduction

Atopic dermatitis (AD) is a chronic inflammatory pruritic dermatosis with a multifactorial etiology. This condition affects 10% to 20% of infants in the US (1) and is a lead diagnosis for many pediatric healthcare visits as it is the eighth most common disease in patients under the age of 25. (2,3) The exact cause of AD is unknown, but genetic factors are considered to play an important role in the development of this disease. In the vast majority of patients with AD, the condition develops during the first 2 years of life, but the likelihood of new disease onset declines and disease severity tends to improve with age although adult populations are still affected as well.

Topical corticosteroids have been the gold standard for the treatment of AD for decades. Recently, newer nonsteroid topical agents such as tacrolimus and pimecrolimus (topical calcineurin inhibitors) have been introduced; however, these agents have had diminished use due to parental and physician concerns regarding long-term safety, despite a lack of substantiating studies. (4,5) Consequently, for the management of steroid responsive dermatoses such as AD, safe and effective lower potency topical steroids will likely remain the cornerstone of therapy, especially in younger patients. Nonetheless, poor patient compliance with topical corticosteroids can often be linked to patient, parent, and care-provider fears of steroid side effects (6,7) or tolerability issues. (8,9) Similarly, validation of the safety of these products has been a practitioner concern especially with respect to their use in very young patients where increased surface to body mass ratios increase the potential risk for systemic as well as local side effects. (10)

During the past 10 years there has been very little innovation in the low potency, class VI, steroid arena. Recently, a novel formulation of desonide has been developed to address the practitioner and patient concerns discussed above. Desonide is a well known synthetic, nonfluorinated corticosteroid with anti-inflammatory and antipruritic properties. The safety and efficacy of desonide as an active pharmaceutical ingredient has been well demonstrated over many years. (11,12) Until recently, only traditional creams, ointments, and lotions were available in this potency class. This new formulation is distinguished as an alcohol and surfactant-free carbopol-based polymer that contains 0.05% (w/w) of micronized desonide. This hydrogel formulation was designed to be mild, free from sensitizing ingredients, moisturizing, cosmetically elegant, and easily applied over a large surface for AD patients aged 3 months and older.

A wide variety of studies have been performed to validate the safety and efficacy of this new product. These studies are notable in that they include patients as young as 3 months of age with a mean BSA involvement of at least 20%. These studies support a very favorable safety, tolerability and efficacy profile for 0.05% desonide hydrogel. This paper focuses on the presentation of the 2 phase III multi-center, randomized, blinded, vehicle-controlled studies in pediatric patients with mild to moderate AD which substantiates the safety, efficacy, and tolerability of this novel hydrogel formulation.

Methods

Two phase III studies of slightly different design were conducted. Both trials were randomized, blinded, vehicle-controlled trials in which neither the subject nor the investigator knew the identity of the assigned test material. Assignment to treatment arms in these studies included a desonide hydrogel to vehicle ratio of 3 to 1 for the first study and a ratio of 2 to 1 for the second study.

Unless specifically noted, analogous methods were used for both phase III studies. Protocols were reviewed and approved by institutional review boards (IRBs). All subjects provided consent prior to participation and subjects less than 18 years of age considered by their IRB to be capable of giving assent, signed a written assent form in addition to having their guardian or parent's consent to participate. The studies were conducted in accordance with the ethical principles originating from the World Medical Association Declaration of Helsinki and International Conference on Harmonization and good clinical practice guidelines.