AD is a chronic immune-mediated inflammatory disease marked by an over-expression of Th2 cytokines, including IL-4 and IL-13. IL-4/IL-13 plays a pivotal role in the signalling pathways that lead to chronic skin inflammation.
AD is estimated to affect about 10-20% of the child population and 3% of the adult population, at some point in their lives.
The therapeutic options are limited and include UV, moisturizers and corticosteroids (topical, oral).
As yet there is no cure available and the cause is unknown.
However, there seems to be a genetic association, and a hygiene hypothesis has been proposed.
In AD, there are disturbances in the composition of the skin microbiome with reduced microbial diversity and an overabundance of Staphylacoccus aureus spp. (S. aureus) compared to healthy controls .
Targeting the IL-4Rα, dupilumab blocks the receptor subunit for IL-4/IL-13, thus reducing the Th2 response.
This action is hypothesized to assist in stabilising the skin microbiome and reducing the abundance of S. aureus.
A double-blind, placebo-controlled randomized clinical trial (NCTO1979016) outlined subcutaneous injection of dupilumab or placebo (400 mg at week 0 and 200 mg every 2 weeks until week 16) to all enrolled subjects.
Age ≥18 years with moderate-severe AD.
Investigator’s Global Assessment (IGA) ≥3 (on the 0-4 IGA scale).
Body surface area ≥10%.
AD present for ≥3 years.
Inadequate response to topical medication.
Clinical score: EASI score, SCORAD (SCORing AD).
Biomarkers: Pulmonary and activation-regulated chemokine (PARC/CCL17) and serum thymus and activation-regulated chemokine (TARC/CCL18) with ELISA kits.
Bacterial abundance: qPCR all bacteria, qPCR S. aureus.
A total of 54 patients met the inclusion criteria and accepted to be enrolled in the study (from 66 patients screened).
Patients were randomized into the treatment or placebo arm and treatment was performed for 16 weeks.
Final follow-up was at 32 weeks.
Prior to treatment the baseline lesional skin was found to have higher bacterial counts, higher S. aureus counts and lower microbial diversity, compared to non-lesional skin.
There were higher TARC and PARC scores of CCL18 and CCL17 respectively, associated with higher concentrations of S. aureus specific DNA (rCFU/cm2).
The microbial diversity was significantly increased during the treatment phases for lesional and non-lesional skin, and the abundance of S. sureus reduced, but there were no significant differences at week 32 (16 weeks from the last infiltration) compared to baseline (unpublished data).
Monoclonal antibody treatment reversed the AD-associated microbial (dysbiotic) signature for as long as patients were receiving treatment:
Clinical score improved
Microbial diversity increased; S. aureus abundance decreased.
More healthy skin microbiome & more healthy skin.
Strong links between the skin microbial community, type 2 inflammation, and AD severity; AD severity is reduced with an improvement in the skin microbiome.
It is still unknown whether S. aureus is causative or only correlated with AD.
There is an interplay between the immune system and the skin microbiome.
With this collection of summaries from selected presentations at SPIN 2019, and interviews with international experts, we hope to share with you some of the highlights of this year’s congress. The international network met … [ Read all ]