Epidemiological survey of the quantity and anatomical position of facial pigmented spots in relation to age in 454 Japanese women.

Facial pigmented spots are one of the phenotypes of skin aging, but no quantitative analysis of spot features such as color intensity, size, anatomical position, and number on the cheek has yet been performed. In the current study, we conducted an epidemiological survey of 454 Japanese women in their 20s to 70s and analyzed age-related changes and site differences of facial pigmented spots. Using image analysis of high-resolution digital facial photographs, 4912 individual pigmented spots were quantified according to color, size, anatomical position, and total number on the cheek. As a result of color analysis, the color intensity of individual pigmented spots increased with aging, significantly so between ages 30s and 50s. The age-related increase in melanin index of facial spots was confirmed in all sites but did not significantly differ between facial subregions. Regarding the size of pigmented spots, the frequency of large spots increased with age, and large spots were detected in all facial sites. The total number of pigmented spots on the entire cheek increased with aging, significantly so between the 20s and 40s. The number of pigmented spots tended to increase from the region near the canthi to the lower cheeks. The number of spots was markedly increased in the buccal regions compared with the infraorbital and zygomatic regions. The data and methodology presented in the current study can link the state of facial pigmentation with the various factors involved in the histological development of pigmented spots, opening new possibilities in the fields of skin pharmacology and dermatology.

Cost-efficacy and pharmacoeconomics of scalp lesions of psoriatic patients in current Japanese health-care insurance system.

Psoriatic scalp lesion is occasionally recalcitrant to topical or systemic treatments including biologic agents. The combined active vitamin D3 /corticosteroids are more expensive despite their marked efficacy. The aim of the present study is to evaluate total costs as well as costs versus efficacy of topical scalp psoriasis treatments under the current Japanese health-care insurance system. A prospective study was performed from the database of an outpatient clinic. The medical costs of scalp psoriasis patients were evaluated in a prospective manner in each case over a total 12-month duration from July 2017 until August 2019. The total cost of the combined active vitamin D3 /corticosteroid gel (combined gel) was higher (¥79 350) than that of topical corticosteroid lotion (¥22 970). The cost versus efficacy of the combined gel was lower (¥2026/cost for the reduction of 1 Psoriasis Scalp Severity Index [1PSSI] score) than that of topical corticosteroid lotion (¥2316/1PSSI). The reduction of PSSI score was observed by changing from topical corticosteroid lotion to topical combined gel. The combined gel showed the best cost efficacy in terms of medical economic burden in the current Japanese insurance system.

Safety, tolerability and efficacy of repeated intravenous infusions of KHK4083, a fully human anti-OX40 monoclonal antibody, in Japanese patients with moderate to severe atopic dermatitis.

BACKGROUND: KHK4083, a fully human anti-OX40 monoclonal antibody, is a potential novel therapeutic option for moderate to severe atopic dermatitis (AD), targeting the immunopathogenic pathways. OBJECTIVE: Assess the safety and tolerability of repeated doses of KHK4083 in patients with moderate to severe AD, and investigate the pharmacokinetics and immunogenicity of KHK4083. Additionally, assess the clinical efficacy and pharmacodynamics as exploratory objectives. METHODS: In this phase 1, single-center, open-label, repeated-dose study, a total of 22 patients received KHK4083 10 mg/kg IV on Day 1, Day 15 and Day 29, and were followed until Day 155. RESULTS: There were no deaths, serious adverse events (SAEs), or discontinuations due to adverse events (AEs). Common treatment-emergent AEs were mild or moderate pyrexia (11 patients, 50.0 %), and chills (8 patients, 36.4 %). No clinically meaningful changes in the laboratory values, vital signs, and electrocardiogram recordings were observed. The Cmax was 267 ± 53 µg/mL and the t1/2 was 303 ± 88 h at Day 29. The overall assessment of antibodies against KHK4083 (immunogenicity) showed low positive responses. Continued improvement in the Eczema Area and Severity Index (EASI) and Investigator's Global Assessment (IGA) scores were observed throughout the study. The mean and median percent changes in thymus and activation-regulated chemokine (TARC) continued to decrease over time to -70.4 and -78.8 % until Day 155. CONCLUSION: Repeated intravenous infusion of KHK4083 had an acceptable safety profile in patients with moderate to severe AD. Sustained improvement in the symptoms of AD was observed after completion of KHK4083 treatment.

Cost-efficacy and pharmacoeconomics of psoriatic patients in Japan: Analysis from a single outpatient clinic.

Compared with topical corticosteroids, topical combined active vitamin D3 /corticosteroids and especially biologics are more expensive despite their marked efficacy in the treatment of psoriasis. The aim of the present study is to evaluate total costs as well as costs versus efficacy of various psoriasis treatments under the current Japanese health-care insurance system. A prospective study was performed from the database of a single clinic located in Hokkaido Prefecture. Cost and quality of life of psoriatic patients were evaluated in a prospective manner during a total of 12 months from March 2017 until June 2018. Quality-adjusted life year (QALY) of biologics was the highest among all treatments. Among the topical treatments, the cost versus efficacy of combined active vitamin D3 /corticosteroid was lowest (¥10 557/1 Psoriasis Area and Severity Index). Furthermore, incremental cost-effectiveness ratio (ICER) of combined active vitamin D3 /corticosteroid was ¥1 024 031/QALY when compared with topical corticosteroid treatment alone. The topical combined active vitamin D3 /corticosteroid treatment showed the best cost-efficacy in terms of medical economic burden.

Epidemiological survey from 2009 to 2012 of psoriatic patients in Japanese Society for Psoriasis Research.

Since 1982, the Japanese Society for Psoriasis Research has conducted annual epidemiological surveys of patients with psoriasis. Kawada et al. have reported data for 1982-2001 and Takahashi et al. have reported data for 2002-2008. The present study evaluated 9290 psoriatic cases according to age and sex (2009-2012). The male : female ratio was 2.08:1 (6281 male patients [67.6%] to 3009 female patients [32.4%]). The most prevalent type was psoriasis vulgaris (85.6% of all cases), which was followed by psoriasis arthropathica (6.0%), psoriasis guttate acuta (3.2%), Zumbusch-type generalized pustular psoriasis (1.8%) and psoriasis erythroderma (1.5%). Psoriasis vulgaris was the most prevalent type for all ages, while psoriasis arthropathica and psoriasis guttate acuta were most prevalent among patients aged less than 65 years. The present survey detected an increased number of cases with comorbid diabetes and/or arthritis symptoms compared with the previous surveys. We found that treatments frequently involved topical corticosteroids (89.7% of cases) and vitamin D3 ointments (78.0% of cases), with a notable increase in the use of vitamin D3 ointments. Systemic treatments were used in 33.3% of cases, including cyclosporin (33.6%), etretinate (19.5%), methotrexate (8.6%), infliximab (11.4%), adalimumab (10.9%) and ustekinumab (6.2%). Phototherapy was used in 30.9% of cases. Although psoralen plus ultraviolet A therapy was the predominant phototherapy during previous studies, the present survey revealed that narrowband ultraviolet B therapy was used in 84.5% of phototherapy-treated cases. Thus, the present survey revealed major changes in treatment trends.

Economic burden of psoriatic patients in Japan: Analysis from a single outpatient clinic.

Topical and systemic agents have dramatically improved the treatment efficacy of psoriasis. Few reports, however, exist describing the economic burden in Japanese psoriatic patients. The aim of the study was to evaluate the total costs as well as cost versus efficacy of topical and systemic treatments of psoriatic patients under the Japanese health insurance system. The retrospective study was performed from the database of our clinic, which is located in Hokkaido Prefecture. Cost and effectiveness of psoriatic patients were evaluated during the 12-month period from April 2015 to March 2016. Data were collected and calculated for the total cost per year, treatment efficacy and cost versus efficacy. The mean total cost of topical corticosteroid treatment was ¥18 184/year and was lowest among the treatments. The systemic treatment with biologics was most expensive and the costs were over ¥400 000/year. Among the topical treatments, calcipotriol/betamethasone dipropionate was most expensive (¥34 693/year). However, cost versus efficacy was not significantly different from that of topical corticosteroid treatments. The cost of secukinumab was highest among all the treatments (¥631 600/year). However, treatment day per cost was lowest of all the psoriasis treatments. Biologics showed the highest cost than topical or systemic treatments. However, they showed most marked efficacy in terms of improving the psoriatic skin lesions.

Cytokine biomarkers to predict antitumor responses to nivolumab suggested in a phase 2 study for advanced melanoma.

Promising antitumor activities of nivolumab, a fully humanized IgG4 inhibitor antibody against the programmed death-1 protein, were suggested in previous phase 1 studies. The present phase 2, single-arm study (JAPIC-CTI #111681) evaluated the antitumor activities of nivolumab and explored its predictive correlates in advanced melanoma patients at 11 sites in Japan. Intravenous nivolumab 2 mg/kg was given repeatedly at 3-week intervals to 35 of 37 patients enrolled from December 2011 to May 2012 until they experienced unacceptable toxicity, disease progression, or complete response. Primary endpoint was objective response rate. Serum levels of immune modulators were assessed at multiple time points. As of 21 October 2014, median response duration, median progression-free survival, and median overall survival were 463 days, 169 days, and 18.0 months, respectively. The overall response rate and 1- and 2-year survival rates were 28.6%, 54.3%, and 42.9%, respectively. Thirteen patients remained alive at the end of the observation period and no deaths were drug related. Grade 3-4 drug-related adverse events were observed in 31.4% of patients. Pretreatment serum interferon-γ, and interleukin-6 and -10 levels were significantly higher in the patients with objective tumor responses than in those with tumor progression. In conclusion, giving repeated i.v. nivolumab had potent and durable antitumor effects and a manageable safety profile in advanced melanoma patients, strongly suggesting the usefulness of nivolumab for advanced melanoma and the usefulness of pretreatment serum cytokine profiles as correlates for predicting treatment efficacy.

Cutaneous S100-negative, CD1a-positive histiocytosis successfully treated with combination therapy of oral methotrexate and corticosteroid.

S100-negative, CD1a-positive histiocytosis is a rare histiocytic disorder characterized by proliferation of histiocytic cells possessing a phenotype of epidermal Langerhans cells except for the lack of S100 expression and Birbeck granules. We report the case of a Japanese man suffering from S100-negative, CD1a-positive histiocytosis. The patient showed numerous smooth erythematous 5-10-mm papules/nodules on most of his body. The key histopathological feature was the presence of dermal infiltrates of non-epidermotropic S100-negative CD1a-positive mononuclear cells. No systemic involvement was detected. Initially bath-psoralen plus ultraviolet A therapy was effective, but the lesions became recalcitrant to this treatment. Methylprednisolone pulse therapy followed by low-dose methotrexate (up to 30 mg/week) in combination with prednisolone (15 mg/day) effectively controlled the skin lesions.