Skin bioMARkers for atopic eczema Therapy evaluation
Research type
Research Study
Full title
Validation 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.
IRAS ID
269415
Contact name
Dipak Patel
Contact email
Sponsor organisation
Sheffield Teaching Hospitals NHS Foundation Trust
Eudract number
2019-002643-23
Clinicaltrials.gov Identifier
Clinicaltrials.gov Identifier
21304/0271/001-0001, MHRA CTA Number
Duration of Study in the UK
1 years, 5 months, 30 days
Research summary
The first-choice drug treatment for mild-moderate eczema is currently a topical corticosteroid. By topical, we mean the treatment is intended for application directly to the skin. Whilst topical corticosteroids are effective at treating eczema, they have been found to cause unwanted skin changes, such as skin thinning, if used inappropriately over long periods of time. Exactly how much unwarranted thinning is caused by different treatment routines is unclear, so we want to use some new non-invasive ways to measure skin thinning to better understand the problem. One of these ways is to take a 3D image of the skin using a technique called OCT, which is similar to ultrasound. Because the methods are so sensitive, the signs of skin thinning can be seen before the skin becomes visibly damaged.
Crisaborole ointment is a new non-steroidal drug treatment for eczema that appears to be as effective as some topical corticosteroids, and is not expected to cause abnormal skin thinning. Betamethasone valerate cream is one of the most commonly prescribed topical corticosteroids for eczema in the UK. Therefore, the aim of this study is to conduct a trial in eczema patients involving treatment of separate areas of their skin with either crisaborole ointment or betamethasone valerate cream. The effects of the treatments will be assessed using the non-invasive skin imaging techniques.
Both treatments have already been tested in clinical trials for clinical efficacy, and so efficacy will not be assessed again here. This study will confirm whether or not crisaborole causes the same unwarranted skin thinning caused by betamethasone valerate in a direct comparison. Having a better understanding of the unwanted effects of these treatments will be informative for prescribers/doctors and patients. The findings will also help identify important ways of measuring skin thinning for use in future clinical trials.Summary of Results
The first-choice drug treatment for mild-moderate eczema is currently a topical corticosteroid. By topical, we mean the treatment is intended for application directly to the skin. Whilst topical corticosteroids are effective at treating eczema, they have been found to cause unwanted skin changes, such as epidermal thinning, if used inappropriately or over long periods of time. Exactly how much unwarranted thinning is caused by different treatment routines is unclear, so we wanted to use some new non-invasive ways to measure skin thinning to better understand the problem. One of these ways is to take a 3D image of the skin using a technique called OCT, which is similar to ultrasound. Because the methods are so sensitive, the signs of underlying skin thinning can be seen before the skin becomes visibly damaged.
Crisaborole ointment is a new non-steroidal drug treatment for eczema that appears to be as effective as some topical corticosteroids, and is not expected to cause abnormal skin thinning. Betamethasone valerate cream is one of the most commonly prescribed topical corticosteroids for eczema in the UK. Therefore, the aims of this study were to conduct a trial in eczema patients involving treatment of separate areas of their skin with crisaborole ointment and betamethasone valerate cream, and to confirm whether crisaborole causes the same unwarranted skin thinning as the corticosteroid. The effects of the treatments were assessed using the non-invasive skin imaging techniques described.
In the SMART study, patients with eczema applied betamethasone valerate 0.1% cream to the underside of one arm and crisaborole 2% ointment to the other every morning and evening for 4 weeks. We assessed the skin on these areas before, during and after treatment. None of the patients had visible signs of eczema on their forearms when the study started.
We found that, after only 2 weeks, the epidermis was around 30% thinner on the arms treated with betamethasone valerate cream. This is more than twice the thinning we observed after 4 weeks of treatment with crisaborole ointment. We also saw changes to the blood vessel arrangement in the skin on arms treated with the steroid cream. After one month of treatment, arms where crisaborole has been applied showed better skin barrier integrity – generally better functioning skin – than arms treated with the betamethasone valerate cream.
We also assessed the skin 4 weeks after treatment finished. Arms treated with crisaborole had almost fully returned to normal by this point but there was still some evidence of thinning on arms treated with betamethasone valerate cream.
From the results of the SMART study, we can say that crisaborole may be a more suitable long-term treatment for people with eczema where thinning of the skin may be likely to happen and cause further problems. The non-invasive imaging techniques used in this trial have identified new important markers of skin health. We can use these techniques in the future to monitor skin changes caused by topical treatments and make better decisions when prescribing.REC name
East Midlands - Derby Research Ethics Committee
REC reference
20/EM/0006
Date of REC Opinion
23 Mar 2020
REC opinion
Further Information Favourable Opinion