ALBUQUERQUE – Symptoms decreased by 51% at 2 weeks and by 73% at 12 weeks in adults with atopic dermatitis who received cyclosporine A therapy in an open-label, single-arm study.
Clinical improvements correlated with suppression of epidermal hyperplasia and decreases in inflammatory biomarkers including S100A7, IL-13, and IL-22, reported Mariya Rozenblit of Mount Sinai Medical Center in New York and her associates. Ms. Rozenblit presented the results at the annual meeting of the Society for Investigative Dermatology, and the findings were published online in the Journal of Allergy and Clinical Immunology (J. Allergy Clin. Immunol. 2014 [doi:10.1016/j.jaci.2014.03.003]).
"This is the first study that establishes a link between Th2/Th22 cytokines and molecular epidermal alterations as well as correlations between clinical improvement and skin biomarkers" in atopic dermatitis, said Ms. Rozenblit and her associates.
To characterize these mechanisms and compare them with clinical outcomes in atopic dermatitis, the researchers treated 19 affected adults, aged 18-69 years, with 5 mg/kg/day of cyclosporine A. Patients were assessed at baseline, week 2, and week 12 using gene expression and immunohistochemistry studies, biopsies of lesional and nonlesional skin, and the Scoring of Atopic Dermatitis (SCORAD) measure.
"Patients had decreases in erythema and edema at week 2, with further reductions at week 12," said Ms. Rozenblit. By week 12, 17 of the 19 patients had SCORAD reductions of at least 50%, the threshold for therapeutic response, she said. The cohort’s SCORAD scores improved by an average of 51% (standard deviation, 23%) at week 2 and by 73% (SD, 18%) at week 12, she added. SCORAD results ranged from 44 to 98 (mean, 65; standard deviation, 16) at baseline, from 5.9 to 76 (mean, 33; SD, 20) at week 2, and from 0 to 59 (mean, 18; SD, 15) at week 12.
Clinical improvements correlated with significant genomic improvements as measured by gene arrays and reverse transcriptase polymerase chain reaction (PCR) testing. In particular, the researchers observed reductions of Th2, Th22, and some Th17-related molecules such as IL-13 and IL-22; modulation of epidermal hyperplasia and proliferation markers K16 and Ki67 also were noted. IL-13 as well as several S100 proteins and IL-22 were among the top genes that were decreased after treatment, said Ms. Rozenblit.
After 12 weeks of treatment, lesional skin biopsies also indicated that the granular layer had improved to the point that it resembled nonlesional skin, Ms. Rozenblit noted. "Baseline lesional skin had substantial inflammatory cell infiltrates, with decreases essentially to baseline nonlesional levels by week 12," she said. Nonlesional skin showed similar but less marked reversal of inflammatory and epidermal measures after cyclosporine A treatment.
As clinical trials investigate better-tolerated targeted agents for atopic dermatitis, understanding the biomarkers involved will provide a reference point for evaluating improvements in tissue inflammation.
Ms. Rozenblit reported no conflicts of interest. The National Institutes of Health, Rockefeller University, and a Dermatology Foundation Physician Scientist Career Development Award helped fund the research. Novartis provided cyclosporine A for U.S. patients.