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COPYRIGHT 2006 Journal of Drugs in Dermatology, Inc.
Abstract
Background: MAS063DP cream has received marketing authorization in the US and the European Union for symptom relief of atopic dermatitis (eczema) and contact dermatitis.
Design: A multicenter, randomized, vehicle-controlled, phase IV study was completed in the US.
Methods: 218 patients aged 18 to 84 years joined this 50-day study. Patients self-administered MAS063DP cream (N=145) or vehicle cream (N=73) 3 times per day to affected areas and those areas prone to be affected. The primary endpoint for efficacy was the change in EASI at Day 22 of treatment, comparing the 2 treatment groups. Secondary outcomes included EASI scores at other time points, IGA, pruritus (100mm VAS), % BSA, and the need for rescue medication.
Results: MAS063DP was statistically (p<.0001) more effective than vehicle in all outcomes at all time points. The incidence of rash was 2.1% in the MAS063DP group versus 5.5% in the vehicle group. Only 2 patients discontinued MAS063DP due to an adverse event.
Conclusion: MAS063DP cream was confirmed to be a safe and effective treatment for mild to moderate atopic dermatitis in adults.
Introduction
Atopic dermatitis (AD) is the most common type of eczematous dermatitis, a group of common inflammatory skin conditions characterized by pruritus, pale, erythematous or violaceous hues, vesiculation, erosion, exudation and crusting, scaling, and lichenification. (1) For the diagnosis of AD, the eczema must have a distribution characteristic for the age of the patient, be accompanied by xerosis and a personal or family history of atopy, be of early onset, and follow a chronic or chronically relapsing course. (2) Studies have shown that AD is a global problem with prevalence of approximately 10%. (3) Patients with AD have an abnormal skin barrier that results in increased transepidermal water loss and enhanced penetration of allergens and microbial organisms, especially S. aureus. (4,5) AD has a significant impact on the quality of life of patients and is a disease that carries a high economic burden. (6) The successful management of AD may require a multi-prong approach that includes the use in a permutational paradigm of systemic agents, some with significant toxicity: phototherapy, topical agents with immunoregulatory and barrier repair functions, and preventive educational and psycho/social intervention. (7)
MAS063DP is a cream containing glycyrrhetinic acid, vitis vinifera, telmestine, capryloyl glycine, shea butter, and hyaluronic acid in a hydrolipidic base that has shown efficacy and safety in both open and randomized, double-blind, vehicle-controlled studies in eczema and AD, in Europe. (8,9) It also showed efficacy in the treatment of irritant contact dermatitis in a recent double-blind vehicle-controlled US study. (10) The 2% glycyrrhetinic acid (GrA) contained in the MAS063DP formulation is believed to contribute to its anti-pruritic and anti-inflammatory properties. 18-[beta]-GrA is the major active metabolite of glycyrrhizin, the main component of the root extract of Glycyrrhiza glabra (licorice). GrA exhibits anti-inflammatory properties in different organs in various animal models (11-12) with a potency comparable to that of indomethacine. (13) A proposed mechanism of action for the anti-inflammatory activities of GrA includes the inhibition of 11-[beta]-hydroxysteroid hydrogenase, an enzyme responsible for the metabolism of cortisol into cortisone (14-16) and the selective inhibition of the classical complement cascade. (17) GrA has a chemical structure related to cortisone and has been shown to potentiate the action of hydrocortisone on skin. (18) A gel formulation containing 2% GrA was recently reported to be effective in the treatment of AD. (19) However, the formulation contains several other agents such as telmestine, sodium hyaluronate, and proanthocyanidines, all of which could theoretically suppress the symptoms or process of inflammation, as well as a novel emulsion formulation intended to rehydrate the tissues and restore the barrier function of the skin. The standardized extract of vitis vinifera (grapevine) in MAS063DP contains proanthocyanidines (OPC), natural substances belonging to the group of bioflavonoids with particular anti-oxidant activity, which synergistically augment the inhibition of membrane lipid peroxidation effects of alpha tocopherol (vitamin E), and other antioxidant enzymes like superoxide dismutase (SOD). (20) OPC decrease pro-inflammatory interleukin 8, over-expressed in AD and irritant contact dermatitis. (21) In addition, OPC form a barrier to the concentration of elastase, hyaluronidase and B-glucuronidase, enzymes involved in the catabolism of elastine, collagen, and hyaluronic acid. (22) These free radical scavenging anti-lipo-peroxidant, antiprotease, and glycosidase actions of OPC are used to explain their in vivo anti-inflammatory effects, (23-24) including anti-erythemal action induced by UV and exogenous variants. (25)
MAS063DP also contains telmesteine, which has antielastase and anticollagenase activity in vitro and inhibits metalloproteinases MMP2 and MMP9 over-expressed in AD and psoriasis. (26,27) Capryloyl glycine is both a preservative for its antibacterial and antimycotic activity (with piroctone olamine), and a vector for glycine (collagen contains 35% glycine). (28) Shea butter in the formulation is from Butyrospermum parkii composed principally of triglycerides and fatty acids including linoleic acid rich in phytosterols and tocopherols, highly purified to eliminate antigenic proteins. Finally, MAS063DP contains hyaluronic acid and glycosaminoglycan, that is part of the ground substance of connective tissue and may play a role in wound healing by enhancing epithelial cell migration and differentiation; it also...
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