The paradigm shift in drug development for atopic dermatitis: Addressing the variables of the equation leading to...

The recent development of new therapies for atopic dermatitis (AD) has greatly benefited from the advances in understanding the mechanisms underlying this disease. This progress now allows one to envisage pushing the therapeutic boundaries beyond the simple symptomatic treatment of the exacerbations of AD and considering new therapeutic strategies aimed to allow an off-therapy long-term and deep remission, that is, disease modification. Owing to the complexity of the phenotype and underlying mechanisms of AD, it is expected that this will not fit to the current one-size-fits-all model in drug development. Thus, aiming at disease modification will lead to a paradigm shift in drug development strategy in AD requiring the consideration of a precision medicine approach with a phenotype-endotype (biomarker)-based stratification as well as a consensus definition of specific study endpoints for the clinical development program. This review addresses the scientific rationale for this strategy, some general aspects of the design of confirmatory clinical trials, and the variables along the Population, Intervention, Comparator, and Outcome framework to be addressed for reaching the ultimate goal of disease modification in AD.