Novel biophysical skin biomarkers discriminate topical anti-inflammatory treatments based on their potential for local adverse effects

Abstract

Background

Topical corticosteroids (TCS) are efficacious treatments for inflammatory skin conditions, however, there is a risk of adverse effects; understanding how best to use these treatments is an unmet research priority shared by patients and healthcare professionals.

Objectives

To develop non-invasive biomarkers of local adverse effects to facilitate the optimisation of topical therapy.

Methods

An observer-blind randomised within-subject controlled trial in atopic dermatitis patients was undertaken (NCT04194814) comparing betamethasone valerate 0.1% cream (BMV) to a non-steroidal anti-inflammatory treatment, crisaborole 2% ointment (CRB). Participants underwent 4 weeks twice-daily treatment with CRB on one forearm and BMV on the other (left/right randomised). Skin properties were assessed on days 1, 15, 29 of treatment and again on day 57, including imaging of skin microstructure using Optical Coherence Tomography (OCT) and Attenuated Total Reflectance (ATR)-Fourier Transform Infrared (FTIR) spectroscopic assessment of stratum corneum molecular structure. The primary outcome was the difference in the change in epidermal thickness from days 1 to 29.

Results

Thirty-seven participants received the first dose, of which 32 completed the study (all 37 were included in the analysis). Pathologic epidermal thinning at day 29 was significantly greater (p < 0.0001) at sites treated with BMV (−31.66; 95% confidence interval: −35.31, −28.01 µm) compared to CRB (−13.76; −17.42, −10.10 µm). From a panel of exploratory biomarkers, superficial plexus depth and stratum corneum carboxyl group levels had the greatest ability to discriminate the effects of the TCS treatment (p < 0.0001).

Conclusions

BMV induced 2.3x more pathologic epidermal thinning than CRB after 4 weeks of treatment, suggesting that CRB may be more appropriate for longer-term, proactive-based, treatment strategies where the risks of adverse effects are greatest. By monitoring treatment effects using OCT and ATR-FTIR spectroscopy, two new non-invasive biomarkers of skin health have been identified with the potential to help optimise future safe treatment strategies.