PracticeUpdate: Dermatology - Winter 2018

IID 2018 25

Two Topical Preparations ShowPromise for Eczema Results of two studies, of topical collagen-derived dipeptide plus Grifola frondosa extract, and SB414 cream, have shown promise against eczema. Results of an open-label, single-center, crossover clinical trial (topical collagen-derived dipeptide + Grifola frondosa extract) and two preclinical studies (SB414 cream) were reported at IID 2018. Topical collagen-derived dipeptide + Grifola frondosa extract K entaro Naito, PhD, of the University of Tsukuba in Japan, set out to assess the efficacy and safety of topical water loss, visual analog scale of pruritus, and observational analysis of the stratum corneum, were performed. Transepidermal water loss revealed that daily application of collagen-derived dipeptide + Grifola frondosa extract lotion to affected areas alleviated eczema signif- icantly vs placebo.

and biopsied for Staph aureus counts and tissue cytokine levels in all treatment groups (interleukins 13, 4, 17A, thymic stro- mal lymphopoietin, and interferon γ). Upregulation of individual cytokines in the untreated group ranged from three- to 18-fold. All cytokine levels in the SB414- treated group, except interleukin 17A, were statistically indistinguishable from unin- fected, baseline tissue cytokine values. Interleukin 4 was reduced by 87% and interleukin 13, by 76% versus mice that received placebo. Thymic stromal lymphopoietin, an initia- tor of the atopic response, and a sensitive marker of chemical irritation, was not elevated in SB414-treated infected or uninfected mice. This lack of elevation demonstrated the local tolerability of the nitric oxide-releasing cream. Staph aureus levels in the skin of SB414- treated mice were decreased to 0.5 x 10 5 colony-forming units, a >90% reduction ver- sus untreated mice and those who were administered vehicle. Importantly, the anti- Staph aureus effects of SB414 were not driven by increased interferon γ tissue cytokine levels. Mr. Hollenbach concluded that the data demonstrated the ability of topically applied 6% SB414 to reduce key Th2 cytokines such as interleukins 4 and 13, and to reduce the Staph aureus burden in a mouse model of atopic dermatitis. www.practiceupdate.com/c/68654

application of collagen-derived dipeptide + Grifola frondosa extract for mild to mod- erate eczema. The 8-week study was composed of 4-week treatments with a lotion containing collagen-derived dipeptide and Grifola frondosa extract and placebo. Initially, 24 patients (20 females and 4 males) with moderate eczema received placebo for 4 weeks. They then received collagen- derived dipeptide + Grifola frondosa extract once daily for 4 weeks. Diagnostic evaluation and clinical eczema- related tests, including transepidermal compared to healthy control skin. At week 12, mean PASI improvement form week 0 of treatment was 87.1%, with 100% of patients achieving at least 75% improvement in mean PASI. From weeks 0–12, the percentage of interleukin 17-expressing CD4-positive T effector cells in lesional skin decreased from 11.6% to 5.8%, vs a baseline percent- age of 7.5% in healthy controls. The percentage of interleukin 17-express- ing CD8-positive T cells decreased from 13.5% to 7.6%, vs 2.0% in controls. The percentage of CD4-positive Treg cell-expressing interleukin 17 decreased from 3.6% to 0.9%, vs to 1.6% among controls. Dr. Yang concluded that secukinumab treatment reduced the percentage of interleukin 17-expressing immune cells greatly in lesioned skin. The proportion of interleukin 17-expressing CD4-positive T effector and Treg cells decreased to levels similar to or below that of healthy controls. Not only CD4-positive Th17 cells, but also CD8- and CD4-positive Treg cells produce interleukin 17 in psoriasis. Secukinumab

Subcutaneous and diagnostic findings remained unchanged following placebo application, but improved significantly fol- lowing application of collagen-derived dipeptide + Grifola frondosa extract lotion. Comparedwith baseline, visual analog scale scores of pruritus were also reduced signif- icantly after application of collagen-derived dipeptide + Grifola frondosa extract lotion. Dr. Naito concluded that a potential benefit, and safety, of collagen-derived dipep- tide + Grifola frondosa extract lotion was suggested for treating mild to moderate eczema. SB414 cream S tanley Hollenbach, BS, of Novan Inc., Morrisville, North Carolina, explained that eczema is a chronic inflamma- tory skin disease in which >90% of patients exhibit Staphylococcus aureus coloniza- tion of lesional skin. Density of Staph aureus colonization has been correlated with both severity of eczema lesions and the degree of cutaneous inflammation. A filaggrin-defect eczema mouse model (FLG ft/ft mice) has been used previously to correlate the depth of Staph aureus skin penetration with upregulation of interleu- kins 4, 13, and other cytokines. Using this model in which mice are first sen- sitized by ovalbumin and then exposed to 1 x 10 6 colony-forming units of Staph aureus , Mr. Hollenbach conducted a pilot study to identify the time course of peak cytokine levels (48 h) after cutaneous infection with Staph aureus . The optimal treatment win- dow, with dosing initiated at 24 h, was determined. In a second study, animals were treated topically after the 24-h Staph aureus incu- bation period, and again 8 h later, with vehicle or 6% SB414. SB414 releases nitric oxide. After 48 h, mice were euthanized

reduces these significantly. www.practiceupdate.com/c/68649

Courtesy of IID 2018

VOL. 2 • NO. 3 • 2018