Targeting IL-13 with tralokinumab may improve microbial dysbiosis in atopic dermatitis

Tralokinumab, a high-affinity monoclonal antibody that specifically neutralizes interleukin-13, improved microbial diversity and reduced Staphylococcus aureus among patients with moderate to severe atopic dermatitis, according to a study.

“Studies have pointed to a lack of microbial diversity and increased bacterial load with pathogenic strains such as Staphylococcus aureus on AD skin,” Lisa A. Beck, MD, of the department of dermatology at the University of Rochester Medical Center in Rochester, New York, and colleagues wrote. “Individuals with AD are colonized with high levels of S. aureus in both lesional and non-lesional skin at approximately 90%, while only 10% of healthy individuals harbor S. aureus.”

The study examined the impact of tralokinumab on microbial diversity in the lesional skin of adults with moderate to severe AD. The examined data was taken from a subset of patients from the 52-week, phase 3 ECZTRA 1 trial, during which adults with moderate to severe AD were randomly assigned 3:1 to subcutaneous tralokinumab or placebo. After a loading dose of tralokinumab 600 mg or placebo, patients received 300 mg of the study drug or placebo every 2 weeks through week 16, at which point those who met the response criteria were randomly assigned 2:2:1 to tralokinumab 300 mg dosed either every 2 or 3 weeks or placebo. Those who did not meet the response criteria at week 16 received open-label tralokinumab 300 mg every two weeks and had the option of also receiving corticosteroids.

During 16 weeks of treatment, S. aureus was reduced from a median 1,157 gene copies per square centimeter to 56 gene copies per square centimeter — a 20.7-fold reduction — in the tralokinumab group compared with a non-statistically significant 2.1-fold reduction of 471 gene copies per square centimeter to 352 gene copies per square centimeter in the placebo group.

Researchers also observed increased microbial diversity in those taking tralokinumab compared with placebo. Relative abundance of major phyla and genera remained the same in lesional skin for placebo-treated participants, whereas the relative abundance of the genus Staphylococcus was reduced 47.5% from baseline in tralokinumab-treated participants by week 16. The decrease in Staphylococcus was due to the decrease in S. aureus from comprising 32% of all bacteria at baseline to less than 8% at week 16.

Staphylococcus argenteus also decreased from 5% of the genus to 2%, whereas the relative abundance of commensal coagulase-negative staphylococci was increased.

“The results for this study are similar to those observed with dupilumab,” Beck and colleagues wrote. “However, the similarity between the results for dupilumab, which targets both [interleukin (IL)]-13 and IL-4 signaling, and tralokinumab, which specifically targets IL-13, suggests that IL-13 may be the key driver of the altered AD skin microbiome, and that targeting only IL-13 is enough to change the microbial dysbiosis in AD skin.”