PracticeUpdate Conference Series: IID 2018

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. 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 sensitized 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 cuta- neous infection with Staph aureus . The optimal treatment window, 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 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 uninfected, baseline tissue cytokine values. Interleukin 4 was reduced by 87% and interleukin 13, by 76% vs mice that received placebo. Thymic stromal lymphopoietin, an initiator 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 vs 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.

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 application of collagen-derived dipeptide + Grifola frondosa extract for mild to moderate 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-de- rived dipeptide + Grifola frondosa extract once daily for 4 weeks. Diagnostic evaluation and clinical ecze- ma-related tests, including transepidermal 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 sig- nificantly vs placebo. Subcutaneous and diagnostic findings remained unchanged following placebo application, but improved significantly following application of collagen-derived dipeptide + Grifola frondosa extract lotion. Compared with baseline, visual analog scale scores of pruritus were also reduced significantly after application of collagen-derived dipeptide + Grifola frondosa extract lotion. Dr. Naito concluded that a potential benefit, and safety, of collagen-derived dipeptide + Grifola frondosa extract lotion was suggested for treating mild to mod- erate eczema. SB414 cream S tanley Hollenbach, BS, of Novan Inc., Morrisville, North Carolina, explained that eczema is a chronic inflammatory skin disease in which >90% of patients exhibit Staphylococcus aureus colonization of lesional skin. Density of Staph aureus colonization has been correlated with both severity of eczema

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Courtesy of IID 2018

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