Comparison of three methods for measuring psoriasis severity in clinical studies (Part 1 of 2): change during therapy in Psoriasis Area and Severity Index, Static Physician's Global Assessment and Lattice System Physician's Global Assessment

BackgroundAccurate and reliable assessment of changes in psoriasis severity is critical in clinical trials of therapies.ObjectiveTo compare Psoriasis Area and Severity Index (PASI), static Physician's Global Assessment (sPGA), and the Lattice System Physician's Global Assessment (LS‐PGA) in a trial of systemic treatments for plaque psoriasis vulgaris and to assess whether they measure change in psoriasis induced by therapy.MethodsPatients were randomized to voclosporin or cyclosporine for 24 weeks (the ‘24‐week‐treatment’ group, n = 366), or placebo for 12 weeks followed by voclosporin for 12 weeks (the ‘initial‐placebo’ group, n = 89).ResultsAll scoring systems changed in concert and were sensitive enough to detect reductions in severity during placebo therapy as well as with active therapy (P < 0.01 for each measurement). At study onset, there were poorer correlations of sPGA with PASI (r = 0.45) and LS‐PGA (r = 0.39) than between PASI and LS‐PGA (r = 0.68). After therapy, all correlations were stronger, but sPGA continued to be less well correlated (with PASI, r = 0.85; with LS‐PGA, r = 0.79) than LS‐PGA with PASI (r = 0.90). Two‐ or three‐step improvements in LS‐PGA showed very good to excellent accuracy in corresponding to PASI‐50 and PASI‐75, respectively, and were more accurate than comparable changes in sPGA.ConclusionPASI, sPGA and LS‐PGA are responsive to the varying degrees of improvement in psoriasis induced by either placebo or active therapy. While the three systems capture similar information, each has different reasons for use in a clinical trial.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/111966/1/jdv13132.pd

角质形成细胞中的 HG 和 KdPT 的影响

Summary 糖尿病是一种常见病,影响全世界数百万人。它表现为血液和身体内的葡萄糖浓度增高。慢性足部溃疡是糖尿病最严重的并发症之一,影响高达 10% 的糖尿病患者。这类溃疡依然难以治疗,导致医疗保健系统成本高昂和患者中的死亡率增高。这项来自德国的研究旨在了解高血糖对表皮角质形成细胞的影响,这种细胞是皮肤最外层的细胞,也是伤口愈合的关键细胞。此外,该研究还调查了一种称为 KdPT 的小分子能否使角质形成细胞免于葡萄糖引发应激和毒性的伤害。作者们在有或无 KdPT 的情况下,通过细胞培养物模型和来自健康受试者的皮肤活检标本调查了角质形成细胞在高糖条件下的各种功能。高糖可减少角质形成细胞的细胞增殖和活力(意味着导致细胞数量减少和健康细胞数量减少)以及迁移(细胞运动)。它还改变了细胞大小和弹性。除了上述发现,还观察到对细胞具有毒性的活性氧簇数量增加和细胞内应激。但是,KdPT 缓解了高血糖的部分负面影响。作者们的这些发现强调了 KdPT 的一种新作用,即,可能被用于开发针对糖尿病皮肤溃疡的新疗法。 Linked Article: Gkogkolou et al. Br J Dermatol 2019; 180:836–84

HG in keratinocytes and the impact of KdPT

Summary Diabetes is a common disease affecting millions of people worldwide. It is characterized by increased glucose concentrations in the blood and body. Chronic foot ulcers are one of the most serious complications in diabetes, affecting up to 10% of diabetic patients. Treatment of these ulcers remains difficult, resulting in high costs for healthcare systems as well as increased mortality in patients. This study from Germany aimed to characterize the effects of high glucose on epidermal keratinocytes, the cells of the outermost layer of the skin and a key cell type for wound healing. Furthermore, it examined if a small molecule, called KdPT, can protect keratinocytes from glucose‐induced stress and toxicity. The authors investigated various functions of keratinocytes under high‐glucose conditions with or without KdPT in cell culture models as well as in skin biopsies from healthy subjects. High glucose reduced cell proliferation and viability (meaning it caused a decrease in the number of cells, and a decrease in the number of healthy cells), and migration (cellular movement) of keratinocytes. It also altered the cell size and elasticity. Parallel to these changes, increased amounts of reactive oxygen species, which are toxic to cells, as well as intracellular stress were observed. However, KdPT reduced some of these negative effects of high glucose. The authors’ findings highlight a novel effect of KdPT, which could be used to develop new treatments for diabetic skin ulcers. Linked Article: Gkogkolou et al. Br J Dermatol 2019; 180:836–84

A Study of the Safety and Efficacy of Calcipotriol and Betamethasone Dipropionate Scalp Formulation in the Long-Term Management of Scalp Psoriasis

BACKGROUND: Effective and safe products are needed for long-term management of scalp psoriasis. This study investigated the long-term safety and efficacy of a two-compound formulation (calcipotriol 50 μg/g plus betamethasone dipropionate 0.5 mg/g) for scalp psoriasis. METHODS: In this 52-week, international, double-blind study, 869 patients with moderate-to-severe scalp psoriasis were randomized to either a two-compound scalp formulation (n = 429) or calcipotriol (n = 440). RESULTS: Adverse drug reactions were less frequent in the two-compound group compared with the calcipotriol group (17.2 vs. 29.5%; p < 0.001). Incidences of adverse events possibly associated with long-term corticosteroid use were low in both the two-compound (2.6%) and the calcipotriol (3.0%) groups. Disease was satisfactorily controlled in 92.3% of visits in the two-compound group versus 80.0% in the calcipotriol group (p < 0.001). CONCLUSION: The two-compound scalp formulation demonstrated a high level of safety and efficacy in long-term management of scalp psoriasis