August 11, 2022
2 minute read
Disclosures: Berdyshev reports receiving research grants from LEO Pharma and Sanofi Genzyme. Please see the study for relevant financial information from all other authors.
Key points to remember:
- Patients treated with dupilumab showed statistically significant improvements in transepidermal water loss.
- Additionally, patients with AD saw rapidly and significantly (P
- These improvements occurred in both lesional and non-lesional skin.
According to a study published in Allergy.
These improvements occurred in both lesional and non-lesional skin, Yevgeny V BerdyshevPhD, an associate professor and researcher in the division of pulmonary care, critical care, and sleep medicine at National Jewish Health in Denver, and colleagues wrote in the study.
According to the researchers, skin lipids known as ceramides are essential for providing the barrier function of the skin. Skin ceramides also include ultra-long chain fatty acids and unique omega-esterified (EO) ceramides that are highly hydrophobic.
IL-4 and IL-13, the main cytokines implicated in the pathogenesis of AD, block the formation of very long chain fatty acids and EO-type ceramides, interfering with skin barrier function and decreasing the total hydrophobicity of cutaneous ceramides. Dupilumab (Dupixent, Sanofi Genzyme/Regeneron) targets the alpha subunit on the IL-4 receptor and blocks signaling initiated by IL-4 and IL-13.
The study cohort (42% female; 80.8% Caucasian) included 26 patients with moderate to severe AD and 26 healthy volunteers. Each group included 20 adults (median age at baseline, 40.5 years; range, 18-63 years) and six adolescents (median age at baseline, 13.5 years; range, 12-17 years).
Patients with AD received 600 mg of dupilumab subcutaneously on day 1, followed by 300 mg every other week, from week 2 to week 14. Patients weighing less than 60 kg received an initial dose 400 mg and subsequent doses of 200 mg.
Patients treated with dupilumab showed statistically significant improvements in transepidermal water loss (TEWL), measured by area under the curve over 10 consecutive skin strips (AUC10). This improvement occurred from baseline to as early as day 15 and was maintained through week 16 (P
The median TEWL AUC10 in the intent-to-treat population was 608 g/m2 × hour (95% CI, 479-737) at baseline and 227 g/m2 × hour (95% CI, 156-299) at week 16, with no significant difference between AD patients and healthy volunteers. Similar results were observed in non-lesional skin.
TEWL results before the skin strip test and after five and 10 skin strips showed similar improvements to the TEWL AUC10 measurements, with statistically significant improvements seen from day 15 to week 16 on lesional skin (P P
Additionally, dupilumab provided levels of esterified omega-hydroxy fatty acids and sphingosine C-18 (EO[C18]S-ceramides) to the levels found in healthy volunteers during treatment, with the greatest effects seen in the first month.
Dupilumab also rapidly restored EOS ceramide levels with longer sphingoid bases in lesional and non-lesional skin, with some restoration of NS ceramide levels with sphingosine C20 and sphingosine C22 in both lesional and non-lesional skin as well. .
Additionally, dupilumab significantly improved the ratio of EOS ceramides to NS ceramides (P
Overall, the researchers wrote, dupilumab restored EOS-ceramide levels and their proportion to corresponding NS-ceramides by restoring the biosynthesis of very long-chain fatty acids, such as IL-4 and IL-13 usually have an impact.