New topical drug development in atopic dermatitis: a place for hope
Authors: C. Paul
Journal: British Journal of Dermatology (2012)

Conflicts of interest C.P. has served as a consultant to Astellas, Novartis and Pierre Fabre and has performed clinical studies for Astellas, Galderma, Novartis and Pierre Fabre. Atopic dermatitis is a chronic disease affecting children and adults with an increasing prevalence in industrialized countries. There are several barriers to topical drug development in atopic dermatitis which may explain the limited number of topical treatment options available today, mainly topical corticosteroids and topical calcineurin inhibitors. Firstly, clinical development programs for new drugs have to run in parallel in children and adults. Secondly, topical drug penetration and permeation issues as well as tolerability of formulations must be considered carefully. Finally, selection of endpoints and evaluation of long‐term treatment strategies are factors which add to the complexity. In this issue of the British Journal of Dermatology, Bissonnette et al. report on the efficacy of a new topical agent, WBI‐1001 in adults with mild to severe atopic dermatitis affecting 3–20% of the body surface area.1 The compound appears to be a stilbene derivative, having both antimicrobial and anti‐inflammatory properties in vitro.2 The authors provide substantial preliminary evidence that the topical agent is effective in atopic dermatitis with some degree of dose–effect relationship, although a wider range of concentrations should have been tested. When looking at the Investigator’s Global Assessment (IGA), a categorical scale frequently considered as a gold standard for atopic dermatitis evaluation, between 50% and 63% of patients experienced treatment success after 6 weeks of twice‐daily treatment. The definition of treatment success in the WBI‐1001 study was less stringent compared with that from the tacrolimus studies, and disease severity was different, making historical efficacy comparisons irrelevant. The level of disease improvement observed with WBI‐1001, if confirmed in subsequent studies, is certainly clinically meaningful. Intriguingly, the 95% confidence intervals for the IGA treatment success rates reported in the article do not include the point estimate, which raises questions. The main limitation of the study is represented by the primary endpoint selection, the mean reduction from baseline in the IGA, a categorical score the researchers inappropriately transformed into a continuous score and expressed as percentage reduction from baseline. Despite these limitations the study results raise new hope for patients and practitioners involved in atopic dermatitis care. Randomized controlled studies against active comparators are needed to understand the relative efficacy of WBI‐1001 vs. topical corticosteroids and calcineurin inhibitors. Pharmacokinetic studies in patients with atopic dermatitis with large body area surface involvement are also required to evaluate the potential for systemic absorption. The local side‐effects described as papular eruption and contact dermatitis in the study need better characterization. Ultimately, meaningful evaluation of treatment effect in atopic dermatitis pivotal trials requires the selection of validated endpoints.3 In this respect, the ongoing international HOME (Harmonizing Outcome Measurements in Eczema) initiative which has already identified core outcome domains relevant to patients, physicians and regulatory representatives should help to facilitate new drug development in atopic dermatitis.4