麻豆传媒

It took as little as 3 days for dupilumab (Dupixent) to achieve substantial decreases in Staphylococcus aureus colonization among adults with moderate-to-severe atopic dermatitis (AD) in a recent trial.

In this randomized, double-blind, placebo-controlled trial, all study participants (n=71) were colonized with S. aureus on their non-lesional and lesional skin surface at baseline. Dupilumab treatment resulted in significant S. aureus reductions after 3 days. As early as day 14-21 of the trial, patients receiving dupilumab saw greater reductions in several AD severity scores compared with the placebo group.

Lisa Beck, MD, is a dermatologist-researcher and principal investigator in the Atopic Dermatitis Research Network at the University of Rochester Medical Center in New York state. She also was the senior author of this report, which appeared recently in . Beck recently discussed the study and its findings with the Reading Room. The exchange has been edited for length and clarity.

What motivated you and this team to pursue this particular research question when it comes to the AD armamentarium?

Beck: For more than 6 years, the biologic called dupilumab which blocks the biologic actions of two key allergic cytokines, IL-4 and IL-13, has been approved by the FDA to treat adults with AD. One of the key questions with targeted new and highly effective therapies is what pathophysiological features of the disease are they improving that are likely to be key drivers of the clinical improvement we observe with dupilumab treatment?

Most studies tend to look 4-6 weeks out, and we realized that by 6 weeks, 85% of the clinical improvement was already seen in the adult trial.

So, we thought, if that's the case, let's do a really deep dive. We wanted to collect biospecimens at very early timepoints into dupilumab treatment and look at changes in the skin bacteria, measures of skin barrier function, and biomarkers indicating blockade of IL-4 and IL-13 pathways. When do they dramatically change? And we can relate that all back to clinical improvement.

How would you summarize your key findings?

Beck: The reduction in the abundance of the bacterial pathogen, S. aureus became evident after only 3 days, and became even more significant with subsequent study visits (days 7, 14, 21, 28, and 42). It appeared to plateau by around 28 days.

This S. aureus reduction was also observed in non-lesional skin. We saw significant improvements in disease severity by 2-3 weeks. So, if we're using that as a marker, this really was dramatically earlier than that.

We also measured lesional and non-lesional barrier function, which is abnormal at both skin sites and is thought to significantly contribute to eczema patients' xerosis. We observed improvement in lesional barrier function after 6 weeks of dupilumab treatment.

What do you think are the underpinnings of this association?

Beck: We are still searching for mechanisms that explain the rapid reduction in S. aureus, which was honestly quite shocking to us. It does not seem to be explained by dupilumab-induced increases in antimicrobial peptides. Our lead hypothesis is that we changed the skin interface in such a way that it promoted so called "good bacteria" to compete against S. aureus. We also believe dupilumab treatment may have enhanced neutrophil functions.

What are your take-home messages for clinicians in light of these findings?

Beck: I think this is promising news for the dermatology community because it suggests that eczema patients who frequently get S. aureus infections of the skin and other organs will get these complications less frequently if they are on dupilumab. But this result may have relevance beyond dermatology as well.

Worldwide, there is a concerted effort to better understand who's at risk for and prophylactically prevent orthopedic S. aureus infections arising from joint replacements. One might wonder if it would be worth studying the effect of a single loading dose of dupilumab in at-risk individuals before they undergo surgery requiring placement of a prosthetic device.