Impact of 1-year treatment with dupilumab on work productivity in Japanese patients with atopic dermatitis.

Atopic dermatitis (AD) places a burden on work productivity. Recently, dupilumab was approved for AD, but its impact on work productivity in Japanese patients has not been reported. Furthermore, data on the effect of long-term treatment with dupilumab on work productivity are limited. We investigated the work productivity and activity in Japanese patients with moderate-to-severe AD, utilizing the Japanese version of the Work Productivity and Activity Impairment (WPAI-AD-Japan) questionnaire. Furthermore, we examined the impact of dupilumab on work productivity. Adult moderate-to-severe AD patients treated with dupilumab for more than 12 months from March 2020 to June 2022 who filled out the WPAI-AD-Japan questionnaire were included. Twenty-eight adult AD patients were analysed. Absenteeism was low (mean: 5.3%), but presenteeism, work productivity loss and activity impairment were high (36.8%, 39.7%, 48.9%, respectively). Significant positive correlations were observed between work productivity loss and visual analogue scale (VAS) score of pruritus and between activity impairment and dermatology life quality index (DLQI). Dupilumab treatment significantly reduced presenteeism, work productivity loss and activity impairment at both 6 and 12 months. The extent of their amelioration was numerically higher at 12 months than at 6 months. The reduction rates in presenteeism, work productivity loss and activity impairment were positively correlated with the reduction rates in DLQI and VAS score of pruritus at 12 months. Dupilumab improved work productivity in Japanese AD patients. Long-term remission of pruritus and improved quality of life are important for comprehensive improvement of work productivity.

Serum levels of angiogenesis-related factors in patients with psoriasis.

Psoriasis is characterized by increased dermal vascularity, indicating that aberrant angiogenesis is associated with the pathogenesis of psoriasis. Data on angiogenesis-related factors in psoriasis patients are limited. We explored serum levels of angiogenesis-related factors in patients with psoriasis, and investigated their association with clinical severity and laboratory data. Psoriasis patients visiting our hospital from April 2013 to April 2018 and healthy controls were included in this study. Serum levels of angiopoietin-1, fibroblast growth factor (FGF)-basic, epidermal growth factor (EGF), platelet endothelial cell adhesion molecule (PECAM)-1, placental growth factor, and vascular endothelial growth factor (VEGF) were measured by LEGENDplex. Serum samples obtained from 10 healthy controls, 18 patients with psoriasis vulgaris (PsV), 24 patients with psoriatic arthritis (PsA), and 13 patients with generalized pustular psoriasis (GPP) were analyzed. The serum angiopoietin-1 level was elevated in the PsV, PsA, and GPP patients. GPP patients had a higher serum VEGF level than healthy controls. In contrast, serum levels of EGF and PECAM-1 were lower in the PsV, PsA, and GPP patients than in healthy controls. The serum FGF-basic level was lower in the PsA and GPP patients than in healthy controls. Serum levels of FGF-basic in PsA and GPP patients, PECAM-1 in PsA patients, and VEGF in GPP patients became closer to the respective levels in healthy controls after systemic therapy. The serum FGF-basic level was positively correlated with the psoriasis area and severity index and the number of circulating eosinophils in GPP patients. The serum VEGF level was correlated positively with the serum C-reactive protein (CRP) level and erythrocyte sedimentation rate, and negatively with the serum albumin level in GPP patients. In conclusion, our exploratory study revealed that psoriasis affects serum levels of certain angiogenesis-related factors. Some of these factors could be biomarkers of treatment outcomes, clinical severity, and systemic inflammation.

Macrophage-derived exosomes induce inflammatory factors in endothelial cells under hypertensive conditions.

Hypertension is one of the most important cardiovascular risk factors and results in macrophage infiltration of blood vessels. However, how macrophages coordinate inflammatory responses with endothelial cells (ECs) remains unclear. In this study, we investigated whether exosomes upregulate the expression of inflammatory factors in ECs under hypertensive conditions. Hypertension was induced in rats by continuous infusion of angiotensin II (Ang II). Exosomes were purified from rat serum by density gradient and ultracentrifugation and used to stimulate human coronary artery ECs (HCAECs). Moreover, the interactions between HCAECs and exosomes from human THP-1-derived macrophages were analyzed. Administration of Ang II enhanced the expression of CD68, a macrophage marker, in rat hearts, suggesting enhanced infiltration of macrophages. In addition, the expression of intracellular adhesion molecule-1 (ICAM1) and plasminogen activator inhibitor-1 (PAI-1), a proinflammatory factor, was increased in hypertensive rat hearts compared with control rats. CD68 protein expression and an increase in the expression of some exosome markers were detected in exosomes from hypertensive rat serum. Moreover, the exosomes upregulated the expression levels of ICAM1 and PAI-1 in HCAECs. The level of miR-17, a negative regulator of ICAM1 expression, was markedly decreased in exosomes from hypertensive rat serum compared with exosomes from control rats. Interestingly, Ang II-stimulated THP-1-derived exosomes also enhanced the expression of ICAM1 and PAI-1 and contained reduced levels of miR-17 compared with exosomes from unstimulated cells. These results suggest that inflammation of ECs under hypertensive conditions is caused, at least in part, by macrophage-derived exosomes.