SMARTValidation of a Novel Composite of Skin Biomarkers as a Primary Outcome Measure for Evaluating the Safety of Treatments for Atopic Dermatitis: a Randomized Controlled Trial (Phase 2) Comparing the Effects of Crisaborole 2% Ointment to Betamethasone Valerate 0.1% Cream on Skin Structure and Function in Participants With Atopic Dermatitis.

The first-line drug treatment for mild-moderate AD are currently topical corticosteroids (TCS) with recognized efficacy. However, their prolonged or inappropriate use, can lead to local adverse effects. Side-effects of topical corticosteroids comprise a variety of skin changes in the sense of skin atrophy thinning of the skin and in some cases development of telangiectasia, spontaneous scars, folliculitis, striae distensae (stretch marks), contact dermatitis, acne or rosacea depending on potency, galenic formulation, patient age and body area to which the medication will be applied, exposure time. Assessing the safety (local adverse effects) of current or new treatments and new treatment approaches using existing treatments through noninvasively monitor on possible early skin (subclinical) changes associated with the local clinical adverse effects of treatment may be an effective step for an enhanced AD treatment management. Primary Aim: To further develop and validate two new non-invasive technologies for the assessment of early sub-clinical skin changes associated with adverse effects and to derive an optimum panel of safety biomarkers for use in future clinical trials of topical anti-inflammatory treatments. The safety of two topical anti-inflammatory treatments for AD will be compared in this clinical trial, with a focus on early sub-clinical signs: crisaborole 2% ointment and betamethasone valerate 0,1% cream. Step 1 involves the collection of data on the early sub-clinical skin changes using the non-invasive technologies: OCT and FTIR spectroscopy. The data from this study will then be used to identify and refine biophysical biomarkers of skin atrophy and skin barrier disruption in steps 2 and 3. Secondary Aim: To determine the relative local skin effects of crisaborole (2%) ointment compared to a potent and moderately potent TCS in participants with mild to moderate AD. The focus is on 'early biomarkers' of 'local skin changes'and not clinical efficacy, which has been established in previous trials. Rationale for selecting the two comparators are related to prescription behaviors in UK (Betamethasone valerate 0,1% cream) and with no reported TCS-like local adverse effects profile (crisaborole 2% ointment)