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Abstract Introduction Palmoplantar pustulosis (PPP) is a pruritic, painful, chronic dermatitis that greatly impacts functioning and quality of life and can be difficult to treat. Approved treatment options for PPP are limited, and many patients do not fully respond to current treatments. Methods This was a randomized, double-blind, placebo-controlled, phase 2 study in Japanese patients with moderate to severe PPP and inadequate response to topical treatment. Patients were randomized 1:1 to receive apremilast 30 mg twice daily or placebo for 16 weeks followed by an extension phase where all patients received apremilast through week 32. PPP Area and Severity Index (PPPASI), modified PPPASI (which evaluates pustules and vesicles separately), and Palmoplantar Severity Index (PPSI) total scores and subscores (erythema, pustules/vesicles, and desquamation/scales) were evaluated over 32 weeks of apremilast treatment. Achievement of ≥ 50% improvement in PPPASI (PPPASI-50) was evaluated at week 16 among baseline demographic and clinical characteristic subgroups. Results At week 16, improvements in total score and subscores for PPPASI, modified PPASI, and PPSI, as well as rates of PPPASI-50 were at least moderately greater with apremilast than placebo. Mean PPPASI total score decreased by − 68.3% from baseline to week 32 with continued apremilast treatment. At week 32, mean change from baseline in PPPASI/modified PPPASI subscores ranged from − 58.5% to − 77.0% with apremilast. At week 32, PPSI total score for physician and patient assessments decreased by − 51.3% and − 40.0%, respectively, with continued apremilast treatment. PPPASI-50 response at week 16 was greater with apremilast versus placebo in most demographic and baseline characteristic subgroups. Conclusions Improvements in all PPPASI and PPSI total scores and subscores observed with apremilast over 16 weeks were maintained through 32 weeks in patients with moderate to severe PPP and inadequate response to topical treatment. Rates of PPPASI-50 response at week 16 were mostly consistent across patient subgroups. ClinicalTrials.gov NCT04057937.

Abstract Introduction Patients with moderate-to-severe psoriasis (PsO) treated with interleukin (IL)-inhibitors may require treatment modification to achieve disease control. This study evaluated discontinuation and switching of IL-inhibitors for PsO patients in Japan. Methods Japan Medical Data Center claims (1/2005–5/2022) were used to identify patients with PsO diagnosis preceding a first IL-inhibitor claim (index date) with ≥ 6 months of eligibility prior. Treatment switch (claim for another biologic) and discontinuation (gap in care ≥ 150% of the days’ supply of the preceding prescription) were assessed up to 24 months following initiation. Censored Kaplan–Meier time-to-event analyses calculated rates, and Cox proportional hazards models estimated hazard ratios (HRs) adjusting for baseline characteristics. Results The study included 1481 unique patients treated with brodalumab (BRO; n = 159), guselkumab (GUS; n = 360), ixekizumab (IXE; n = 279), risankizumab (RIS; n = 327), secukinumab (SEC; n = 366), tildrakizumab (n = 40; excluded due to limited data), and ustekinumab (UST; n = 262). At 12/24 months, 25.9%/38.6% of patients overall had discontinued their index IL-inhibitor and 13.5%/21.2% had switched to another biologic. Discontinuation at 12/24 months was lowest for RIS (11.2%/17.4%), followed by UST (17.9%/32.2%), IXE (27.0%/37.0%), GUS (29.8%/43.0%), SEC (35.6%/53.8%), and BRO (37.2%/47.2%). Switching showed a similar trend: RIS (5.7%/10.7%), UST (11.2%/19.9%), SEC (14.7%/25.7%), IXE (14.8%/21.5%), GUS (16.9%/23.2%), and BRO (19.7%/26.8%). HRs of discontinuation relative to RIS were 2.07 for UST, 2.59 for IXE, 2.70 for GUS, 3.65 for BRO, and 3.69 for SEC (all P ≤ 0.001). HRs of switching relative to RIS were 2.05 for IXE, 2.45 for GUS, 2.67 for SEC, 2.73 for UST, and 2.77 for BRO (all P ≤ 0.01). Conclusion Treatment modification of IL-inhibitors for PsO was commonly observed and could indicate insufficient disease control and/or incremental economic burden. Discontinuation and switching rates were lowest for RIS regardless of time point and adjustment for patient characteristics.

Abstract Janus kinase (JAK) inhibitors are efficacious for atopic dermatitis (AD). However, some patients receiving JAK inhibitors develop acne, especially younger patients, or herpes zoster, especially elderly patients, and desire to switch to dupilumab. We experienced two patients with immediate exacerbation of AD after switching from upadacitinib to dupilumab, and herein report these cases. This phenomenon is attributed to the difference in elimination half‐life of the two drugs and a slower onset of efficacy of dupilumab than upadacitinib. When switching from a JAK inhibitor to dupilumab, short‐term concomitant use, intensifying topical treatment, and/or rescue with cyclosporine should be considered.

Abstract Dupilumab was approved for treating adult patients with atopic dermatitis (AD) refractory to topical therapy in Japan in April 2018, and self‐injection of dupilumab has been available since May 2019. Subcutaneous self‐injection of medication has benefits for patients and the healthcare system. However, anxiety about self‐injection, lack of confidence, and the complicated procedure could prevent initiating self‐injection. In this study, we assessed the experience of AD patients treated with dupilumab before and after introducing self‐injection, utilizing the Self‐Injection Assessment Questionnaire (SIAQ). Adult AD patients who received dupilumab by self‐injection and had been treated for more than 3 months after initiating self‐injection in our hospital from March 1, 2020, to June 19, 2021, were included in this study. Patients rated their perceptions about self‐injections using the SIAQ before the first self‐injection and 3 months after initiating self‐injection. Data were collected retrospectively from their charts. Data on 36 patients were analyzed. The mean age was 34.1 ± 11.5 years. Twenty patients used a prefilled auto‐injector, and the others used a prefilled syringe. Scores on self‐confidence and satisfaction with self‐injection significantly improved after introducing self‐injection. Feelings about injections improved in patients over 40 years and in those who felt anxious about self‐injection. A strong correlation in scores between satisfaction with self‐injection and the ease of use was observed. The results were not affected by clinical severity, gender, or device. Our results could encourage patients who dither to introduce self‐injection of dupilumab due to anxiety and/or lack of self‐confidence about self‐injection to initiate self‐injection.

Abstract Background Generalized pustular psoriasis (GPP) is a rare and often refractory disease, and GPP flares can be life threatening. The rarity of GPP prevents the development and evaluation of effective GPP‐specific treatments and obstructs disease understanding. Objectives To evaluate the frequency and severity of GPP flares and the clinical background and treatment history of patients with GPP in Japan. Methods This retrospective, longitudinal, Japanese chart review study included patients diagnosed with GPP (according to Japanese Dermatological Association [JDA] diagnostic criteria), with ≥6 months of continuous observation within 10 years of protocol approval at study sites. Primary outcomes: the frequency and severity of GPP flares during follow‐up. Secondary outcomes: patient characteristics (at time of initial GPP diagnosis) and GPP treatment during follow‐up. Results Overall, 205 Japanese patients were included; 106/205 (51.7%) were male, 146/205 (71.2%) were aged

In the past, psoriasis was considered a skin disease caused only by keratinocyte disorders. However, the efficacy of immunosuppressive drugs and biologics used to treat psoriasis proves that psoriasis is an immune-mediated disease. Indeed, a variety of immune cells are involved in the pathogenesis of psoriasis, including dendritic cells, Th17 cells, and resident memory T cells. Furthermore, keratinocytes play a role in the development of psoriasis as immune cells by secreting antibacterial peptides, chemokines, tumor necrosis factor-α, interleukin (IL)-36, and IL-23. These immune cells and skin cells interact and drive the aberrant differentiation and proliferation of keratinocytes. This crosstalk between keratinocytes and immune cells critical in the pathogenesis of psoriasis forms an inflammatory loop, resulting in the persistence or exacerbation of psoriasis plaques.

Abstract Introduction Evidence on treatment effectiveness in patients with psoriasis having anxiety or depressive symptoms helps shared decision-making. This single-arm, open-label, prospective study—ProLOGUE—was conducted to assess the effectiveness of brodalumab on self-assessed anxiety and depressive symptoms in Japanese patients with psoriasis. Methods Patients aged ≥ 18 years with plaque psoriasis without peripheral arthritis symptoms who had responded inadequately to current therapies were enrolled at 15 Japanese facilities and received brodalumab 210 mg subcutaneously. Results A total of 73 patients were enrolled (male, 82%; median age, 54 years). The proportion of patients without anxiety symptoms changed significantly from baseline (72.6%) to weeks 12 (88.9%, p = 0.008) and 48 (87.7%, p = 0.02); the proportion of patients without depressive symptoms did not change significantly. The Generalized Anxiety Disorder-7 score (median [quartile(Q)1–Q3], 1.0 [0.0–5.0] at baseline; 0.0 [0.0–2.0] at week 12, p = 0.008; and 0.0 [0.0–1.0] at week 48, p = 0.007) and Patient Health Questionnaire-8 score (median [Q1–Q3], 2.0 [0.0–4.0] at baseline; 1.0 [0.0–4.0] at week 12, p = 0.03; and 0.0 [0.0–2.0] at week 48, p = 0.004) significantly decreased after treatment. The median Psoriasis Area and Severity Index scores after treatment were

Abstract Introduction Bimekizumab treatment resulted in improved clinical outcomes in patients with moderate-to-severe plaque psoriasis in BE VIVID, a 52-week, phase 3, randomized, ustekinumab and placebo-controlled study. We present data from the BE VIVID Japan patient subpopulation. Methods Globally, patients were randomized to receive bimekizumab 320 mg every 4 weeks (Q4W), ustekinumab (45/90 mg weight-based at baseline and week 4, then every 12 weeks), or placebo (Q4W through week 16, then bimekizumab 320 mg Q4W). Efficacy endpoints included week 16 Psoriasis Area and Severity Index (PASI) 90 and Investigator’s Global Assessment (IGA) 0/1, and other outcomes [PASI 100, PASI 75, IGA 0, Dermatology Life Quality Index (DLQI) 0/1, absolute PASI, scalp IGA, Psoriasis Symptoms and Impacts Measure (P-SIM) responses]. Safety analyses were conducted. Results There were 108 Japanese randomized patients (bimekizumab: 62; ustekinumab: 29; placebo: 17). At week 16, bimekizumab-treated patients had a higher clinical response versus ustekinumab and placebo (PASI 90: 85.5% versus 51.7% and 5.9%; IGA 0/1: 82.3% versus 48.3% and 0.0%). Over 52 weeks, improved clinical response was maintained with bimekizumab, including patients switching from placebo at week 16. Overall, the safety profile in Japanese patients was consistent with that observed in the global population. Conclusion Bimekizumab resulted in improved clinical response versus ustekinumab and placebo, and was well-tolerated in Japanese patients. Trial registration NCT03370133. Graphical Abstract

Recently, Jak inhibitors such as baricitinib, upadacitinib, and abrocitinib were approved for the treatment of atopic dermatitis (AD) in addition to biologics, including dupilumab, tralokinumab, and nemolizumab. The increase in treatment options can be a benefit to patients with AD. Meanwhile, it could make it difficult for physicians to choose the best treatment among those treatment options. Biologics and Jak inhibitors differ in efficacy, safety, route of administration, and whether or not there is a concern about immunogenicity in addition to the evidence on comorbidities. Among the three Jak inhibitors, the degree of inhibition of signal transducer and activator of transcription differs in each Jak inhibitor. Therefore, the efficacy and safety profiles of the three Jak inhibitors are different. Physicians who treat patients with AD with Jak inhibitors and biologics need to understand the current evidence and choose the best treatment for individual patients. In this review, we discuss how integrating knowledge of the mechanisms of action of Jak inhibitors and biologics, the potential significant adverse events of these drugs, and the age and comorbidities of the patient can help achieve optimal clinical benefit for patients with moderate-to-severe AD refractory to topical agents.

Abstract Dupilumab demonstrated high efficacy and tolerable safety profiles in moderate‐to‐severe atopic dermatitis (AD) patients in clinical trials; however, certain patients suffer from facial redness, while obtaining good responses on the trunk and limbs to dupilumab in the real‐world setting. In our study, we investigated the effectiveness of tacrolimus ointment on facial lesions refractory to topical corticosteroid in patients with AD receiving dupilumab. This study included Japanese adult patients with moderate‐to‐severe AD who developed facial lesions during dupilumab treatment and whose facial lesions became refractory to topical corticosteroid treatment. Nine patients (one female, eight males) were included in this study. One patient newly developed facial erythema after initiating dupilumab. Facial lesions were refractory to dupilumab treatment in the other patients. Five of the nine patients showed improvement in EASI scores of head and neck by switching the facial treatment from topical corticosteroid to tacrolimus ointment. The patient who developed newly facial erythema showed improvement after applying tacrolimus ointment. Although we explored the predictors of effectiveness of tacrolimus ointment in patients with facial lesions during dupilumab treatment, no significant differences were observed in age, duration of dupilumab prior treatment, or prior head and neck EASI between patients who showed improvement after changing to tacrolimus and those who did not. Tacrolimus ointment is worth trying if facial lesions are refractory to topical corticosteroid.

This case report describes a 44‐year‐old male patient with atopic dermatitis who developed malignant lymphoma (diffuse large B‐cell lymphoma) during the dupilumab treatment.

Psoriasis is a chronic inflammatory skin disease characterized by scaly indurated erythema. This disease impairs patients’ quality of life enormously. Pathological findings demonstrate proliferation and abnormal differentiation of keratinocytes and massive infiltration of inflammatory immune cells. The pathogenesis of psoriasis is complicated. Among immune cells, dendritic cells play a pivotal role in the development of psoriasis in both the initiation and the maintenance phases. In addition, it has been indicated that macrophages contribute to the pathogenesis of psoriasis especially in the initiation phase, although studies on macrophages are limited. In this article, we review the roles of dendritic cells and macrophages in the pathogenesis of psoriasis.

Abstract is missing (Short communication)

Atopic dermatitis (AD) is a chronic inflammatory skin disease with pruritus, characterized by recurrent eczema with exacerbations and remissions. AD impairs patients’ QOL and places a heavy burden on patients. Recently, dupilumab, an anti–IL-4Rα antibody, was approved for the treatment of patients with moderate-to-severe AD who are refractory to topical agents and/or conventional systemic therapy. Clinical trials of dupilumab for AD demonstrated high efficacy and tolerable safety profiles. Furthermore, real-world evidence of dupilumab for AD is accumulating. Most of these data show favorable effectiveness and safety profile; however, they also clarified issues, including conjunctivitis and facial redness. There are still a certain number of patients with significant failure. In this article, we review real-world evidence of dupilumab for AD, identify concerns specific to dupilumab, and discuss unmet needs and issues to be addressed in the future.

Systemic plasmacytosis is a rare skin disorder characterized by marked infiltration of plasma cells in the dermis. IgG4-related disease is pathologically characterized by lymphoplasmacytic infiltration rich in IgG4+ plasma cells, storiform fibrosis, and obliterative phlebitis, accompanied by elevated levels of serum IgG4. Reports of cases of systemic plasmacytosis with abundant infiltration of IgG4+ plasma cells has led to discussion about the relationship between systemic plasmacytosis and IgG4-related disease. This study examined IgG4+/IgG+ plasma cell ratios in 4 patients with systemic plasmacytosis and 12 patients with other skin diseases that show marked infiltration of plasma cells. Furthermore, we examined whether these cases met one of the pathological diagnostic criteria for IgG4-related disease (i.e. IgG4+/IgG plasma cells ratio of over 40%). Only one out of 4 patients with systemic plasmacytosis met the criterion. These results suggest that systemic plasmacytosis and IgG4-related disease are distinct diseases.

Objective: To develop N. dimidiatum-specific single PCR-based identification with DNA sequences of nuclear ribosomal internal transcribed spacer (ITS) 1 region primers to facilitate the rapid and accurate detection of N. dimidiatum. Methods: N. dimidiatum-specific PCR primers were designed based on the sequence of the internal transcribed spacer 1 region, which is located between 18S and 5.8S nuclear rDNA. Fungal DNA extracted from common causative species for superficial fungal infection including: 2 strains of N. dimidiatum, 9 species of dermatophyte (DMP) and 25 species of non-dermatophyte (NDM) colonies grown on culture plates were used for PCR analysis. Also, 30 clinical specimens collected from 30 patients clinically diagnosed with fungal nail and feet infection who attended Dermatology clinic Siriraj Hospital during October 2015 to November 2015 were used for PCR assay. Results: Using N. dimidiatum-specific PCR primers, the PCR product was amplified from two standard strains of N. dimidiatum, and there was no amplification from other DMP or NDM species. Regarding sensitivity as lower limit of detection, this PCR method was able to detect 10 pg of N. dimidiatum DNA with ethidium bromide staining and could detect N. dimidiatum in clinical samples. Conclusion: This newly developed N. dimidiatum-specific PCR identification system is rapid, sensitive, and specific. This diagnostic method will facilitate early and accurate diagnosis and accelerate appropriate treatment in patients with N. dimidiatum infection.

Abstract is missing (Short communication)

BACKGROUND: Bortezomib is a proteasome inhibitor that has shown impressive efficacy in the treatment of multiple myeloma. In mice, the addition of dextran sulfate sodium (DSS) to drinking water leads to acute colitis that can serve as an experimental animal model for human ulcerative colitis. METHODOLOGY/PRINCIPAL FINDINGS: Bortezomib treatment was shown to potently inhibit murine DSS-induced colitis. The attenuation of DSS-induced colitis was associated with decreased inflammatory cell infiltration in the colon. Specifically, bortezomib-treated mice showed significantly decreased numbers of CD4(+) and CD8(+) T cells in the colon and mesenteric lymph nodes. Bortezomib treatment significantly diminished interferon (IFN)-γ expression in the colon and mesenteric lymph nodes. Furthermore, cytoplasmic IFN-γ production by CD4(+) and CD8(+) T cells in mesenteric lymph nodes was substantially decreased by bortezomib treatment. Notably, bortezomib enhanced T cell apoptosis by inhibiting nuclear factor-κB activation during DSS-induced colitis. CONCLUSIONS/SIGNIFICANCE: Bortezomib treatment is likely to induce T cell death, thereby suppressing DSS-induced colitis by reducing IFN-γ production.

Cathepsin B (CTSB) is a proteolytic enzyme potentially modulating angiogenic processes and extracellular matrix remodeling. While matrix metalloproteinases are shown to be implicated in tissue fibrosis and vasculopathy associated with systemic sclerosis (SSc), the role of cathepsins in this disease has not been well studied. The aim of this study is to evaluate the roles of CTSB in SSc. Serum pro-CTSB levels were determined by enzyme-linked immunosorbent assay in 55 SSc patients and 19 normal controls. Since the deficiency of transcription factor Fli1 in endothelial cells is potentially associated with the development of SSc vasculopathy, cutaneous CTSB expression was evaluated by immunostaining in Fli1(+/-) and wild type mice as well as in SSc and control subjects. The effects of Fli1 gene silencing and transforming growth factor-β (TGF-β) on CTSB expression were determined by real-time PCR in human dermal microvascular endothelial cells (HDMECs) and dermal fibroblasts, respectively. Serum pro-CTSB levels were significantly higher in limited cutaneous SSc (lcSSc) and late-stage diffuse cutaneous SSc (dcSSc) patients than in healthy controls. In dcSSc, patients with increased serum pro-CTSB levels showed a significantly higher frequency of digital ulcers than those with normal levels. CTSB expression in dermal blood vessels was increased in Fli1(+/-) mice compared with wild type mice and in SSc patients compared with healthy controls. Consistently, Fli1 gene silencing increased CTSB expression in HDMECs. In cultured dermal fibroblasts from early dcSSc, CTSB expression was decreased compared with normal fibroblasts and significantly reversed by TGF-β1 antisense oligonucleotide. In conclusion, up-regulation of endothelial CTSB due to Fli1 deficiency may contribute to the development of SSc vasculopathy, especially digital ulcers, while reduced expression of CTSB in lesional dermal fibroblasts is likely to be associated with skin sclerosis in early dcSSc.

Background: Generalized pustular psoriasis (GPP) is a rare and highly heterogene)ous skin disease, characterized by flares of neutrophilic pustules and erythema. As a rare disease with few clinical studies and no standardized management approaches, there is a paucity of knowledge regarding GPP. Objectives: Conduct a Delphi panel study to identify current evidence and gain ad)vanced insights into GPP. Methods: A systematic literature review was used to identify published literature and develop statements categorized into four key domains: clinical course and flare defi)nition; diagnosis; treatment goals; and holistic management. Statements were rated on a Likert scale by a panel of dermatologists in two rounds of online questionnaires; the threshold for consensus was agreement by ≥80%. Results: Twenty-one panellists reached consensus on 70.9%, 61.8%, 100.0% and 81.8% of statements in the ‘clinical course and flare definition’, ‘diagnosis’, ‘treat)ment goals’ and ‘holistic management of GPP’ domains, respectively. There was clear consensus on GPP being phenotypically, genetically and immunologically distinct from plaque psoriasis. Clinical course is highly variable, with an extensive range of complications. Clinical and histologic features supporting GPP diagnosis reached high levels of agreement, and although laboratory evaluations were considered help)ful for diagnosis and monitoring disease severity, there was uncertainty around the value of individual tests. All acute and long-term treatment goals reached consensus, including rapid and sustained clearance of pustules, erythema, scaling and crust, clearance of skin lesions and prevention of new flares. Potential triggers, associated comorbidities and differential diagnoses achieved low rates of consensus, indicating that further evidence is needed. Conclusions: Global consensus between dermatologists was reached on clinically meaningful goals for GPP treatment, on key features of GPP flares and on approaches for assessing disease severity and multidisciplinary management of patients. On this basis, we present a management algorithm for patients with GPP for use in clinical practice. [ABSTRACT FROM AUTHOR]

Introduction Real-world studies complement randomized controlled trials (RCT), providing treatment-pattern and effectiveness data within a heterogenous population. In several RCTs, dupilumab has demonstrated a robust efficacy profile in patients with moderate-to-severe atopic dermatitis (AD). The main objectives of the ongoing GLOBOSTAD (NCT03992417) study are characterizing the patient population treated with dupilumab, their usage patterns, long-term effectiveness, and safety of dupilumab in real-world AD treatment. However, clinical practice details can differ among countries and/or regions. Objectives: To give a comprehensive overview of patients in Japan enrolled in the GLOBOSTAD study -demographics, history of comorbidities, prior AD treatments, and reasons for initiating dupilumab treatment at baseline; to report on dupilumab effectiveness through physician-assessed AD clinical tools and patient-reported outcomes; and to provide a summary of adverse events one year after initiating dupilumab treatment. Methods: The GLOBOSTAD five-year, multinational, prospective, observational study enrolled patients aged =12 years with moderate-to-severe AD. Patients received dupilumab based on country-specific prescribing information. In Japan, dupilumab is indicated for patients with moderate-to-severe AD who have not responded adequately to topical anti-inflammatory treatments.1 Assessments were performed at baseline, 3 months (M; ±1M), 6M (±2M), and 12M (±2M). Data are reported as observed for enrollment/safety (N=118; data cutoff: March 2023) and follow-up (N=114) populations. Results: Of the 118 patients enrolled in Japan in the GLOBOSTAD study, 69 (58.5%) were aged 18 to 39 years and 43 (36.4%) aged 40 to 64, with mean (standard deviation, SD) age of 37.2 (14.2) years. The population comprised 84 (71.2%) male and 34 (28.8%) female patients. Prior to enrollment, one or more comorbidities were reported in 66 (55.9%) patients, of which type 2 inflammatory comorbidities, such as allergic rhinitis (45; 38.1%), asthma (27; 22.9%), and food allergies (20; 16.9%), were the most frequently reported. Thirty-three (28.0%) patients reported using systemic AD treatments prior to enrollment, primarily systemic immunosuppressants (17; 14.4%) and systemic corticosteroids (13; 11.0%). Eighty (67.8%) patients reported using non-systemic treatments for AD, including topical corticosteroids (70; 59.3%) and topical calcineurin inhibitors (25; 21.2%). The predominant reason for initiating dupilumab treatment was previous treatment failure (95; 80.5%). Dupilumab treatment was initiated in 117 patients with a loading dose of 600 mg dupilumab, and in 1 patient with 300 mg dupilumab. During the study, mean (SD) Eczema Area and Severity Index (EASI; >21=severe; ≤7=mild/no disease) score rapidly improved from 30.2 (12.3) at baseline to 9.3 (10.3) at 3M, and further to 6.5 (8.2) at 6M and 4.6 (7.5) at the end of observation period (12M). Similarly, mean (SD) patient-reported pruritus Numerical Rating Scale (NRS) score improved from 5.6 (2.4) at baseline to 1.9 (2.1) at 3M, and further to 1.5 (1.9) at 6M and 1.2 (1.6) at 12M. Dupilumab-related adverse events were reported in 30 (25.4%) patients; no events led to dupilumab discontinuation. Conclusion: Most adults with moderate-to-severe AD enrolled in the GLOBOSTAD study in Japan reported previously using systemic and/or non-systemic AD treatments; previous treatment failure was cited as the main reason for dupilumab initiation. In line with the local indication, in the 12 months prior to dupilumab initiation, reported systemic immunosuppressant use was less, whereas reported TCS/TCI use was greater, compared to the total GLOBOSTAD population.2 Real-world effectiveness of dupilumab was evaluated using clinical AD tools and patient-reported outcomes; EASI and pruritus NRS scores rapidly improved when patients initiated dupilumab treatment. Improved scores were sustained through the end of the one-year observation period, and safety data were consistent with previous studies. Similar to the overall population enrolled in the GLOBOSTAD study, patients in Japan achieved clinically meaningful improvements in AD signs/symptoms on initiating dupilumab treatment. [ABSTRACT FROM AUTHOR]

Introduction In multiple randomized controlled clinical trials, dupilumab demonstrated robust efficacy in patients with moderate-to-severe atopic dermatitis (AD). Long-term effectiveness of dupilumab in real-world AD treatment is one of the main objectives of the ongoing GLOBOSTAD study. Comprehensive data on Asian patients with moderate-to-severe AD treated with dupilumab are limited. Objectives: To report patient-reported outcomes and physician-assessed AD clinical measures to evaluate disease characteristics, severity, and treatment effectiveness 1 year after initiating dupilumab treatment in Asian patients. The baseline disease severity and patient demographics have been reported previously. Methods: This 5-year, multinational, multicentre, prospective, observational study (GLOBOSTAD; NCT03992417) included Asian patients ≥12 years-old with moderate-to-severe AD who initiated dupilumab treatment based on country-specific prescribing criteria. Eczema Area and Severity Index (EASI), Scoring Atopic Dermatitis (SCORAD), Patient-Oriented Eczema Measure (POEM), Peak Pruritus Numerical Rating Scale (PP-NRS) and Dermatology Life Quality Index (DLQI) were assessed at baseline, 3 months (± 1 month), 6 months (± 2 months), and 12 months (± 2 months). Data are reported as observed in patients self-reported as Asian for enrolment/safety (N = 204; data cutoff: March 2023) and follow-up (N = 194) populations. Results: During the study, EASI (>21 = severe; ≤7 = mild/no disease) score improved from 28.0 (12.1), mean (SD) at baseline to 7.4 (8.5) at 3 months, 5.7 (6.9) at 6 months, and was sustained until the end of observation period, 12 months, at 4.7 (7.1). Similarly, SCORAD (>50 = severe; <25 = mild/no disease) score improved from 61.5 (16.9) at baseline to 25.4 (16.6) at 3 months, 22.5(14.8) at 6 months, and further improved to 18.6 (13.3) at 12 months. During the study, patients also reported early improvements in POEM, mean (SD) from 19.1 (7.3) at baseline to 8.0 (5.8) at 3 months, 7.6 (5.5) at 6 months, and to 7.2 (5.0) at end of observation period (12 months); PP-NRS decreased from 5.7 (2.3) to 2.1 (2.2) to 1.7 (1.8), and to 1.4 (1.7) at 3 months, 6 months, and 12 months respectively; and DLQI improved from 13.2 (7.4) to 4.9 (4.6) to 4.0 (3.8), and to 4.1 (4.0) at 3 months, 6 months and 12 months respectively. Dupilumab-related adverse events were reported in 44 (21.5%) patients while 4 (2.0%) reported dupilumab-related severe adverse events. Conclusion In Asian patients, the initiation of dupilumab treatment led to early improvements in all AD outcome measures, sustained throughout the 1-year observational period. Safety and treatment effectiveness were consistent with overall population. [ABSTRACT FROM AUTHOR]

Objectives. Chemerin is a member of adipocytokines with a chemoattractant effect on plasmacytoid dendritic cells and macrophages and pro-angiogenic properties. We investigated the potential role of chemerin in the development of SSc. Methods. Chemerin expression was evaluated by immunostaining and/or real-time quantitative RT-PCR in human and murine skin. The mechanisms regulating chemerin expression in dermal fibroblasts and endothelial cells were examined using the gene silencing technique and chromatin immunoprecipitation. Serum chemerin levels were determined by ELISA in 64 SSc patients and 19 healthy subjects. Results. In SSc lesional skin, chemerin was up-regulated in small blood vessels, while it was downregulated in fibroblasts surrounded with thickened collagen bundles. The decreased expression of chemerin was significantly reversed by TGF-b1 antisense oligonucleotide in cultured SSc dermal fibroblasts and chemerin expression was markedly decreased in dermal fibroblasts of bleomycin-treated mice. Gene silencing of transcription factor Fli1, which binds to the chemerin promoter, induced chemerin expression in human dermal microvascular endothelial cells and Fli1+/- mice exhibited elevated chemerin expression in dermal blood vessels. Serum chemerin levels inversely correlated with estimated glomerular filtration rate in SSc patients with renal dysfunction. In SSc patients with normal renal function, patients with digital ulcers had higher serum chemerin levels than those without. Conclusion. Chemerin is down-regulated in SSc dermal fibroblasts by autocrine TGF-b, while it is upregulated in SSc dermal blood vessels through endothelial Fli1 deficiency. Increased chemerin expression in dermal blood vessels may be associated with the development of digital ulcers in SSc. [ABSTRACT FROM AUTHOR]

Angiopoietin-like protein 3 (ANGPTL3), which is part of a family of secreted glycoproteins that are structurally similar to angiopoietins, is principally expressed in the liver and is involved in lipid metabolism and angiogenesis. The aim of this study was to determine the clinical significance of serum ANGPTL3 levels, measured with a specific enzyme-linked immunosorbent assay, in patients with systemic sclerosis. Serum ANGPTL3 levels correlated positively with skin score in diffuse cutaneous systemic sclerosis with a disease duration ≤ 6 years. Furthermore, the prevalence of digital ulcers was significantly higher in patients with elevated serum ANGPTL3 levels than in other patients. Moreover, among patients excluding diffuse cutaneous systemic sclerosis with disease duration ≤ 6 years, serum ANGPTL3 levels correlated positively with estimated right ventricular systolic pressure. In conclusion, ANGPTL3 may contribute to the development of progressive skin sclerosis and proliferative obliterative vasculopathy, such as digital ulcers and pulmonary vascular involvement leading to pulmonary arterial hypertension, in systemic sclerosis. [ABSTRACT FROM AUTHOR]

Angiogenesis is a crucial process in the growth and progression of cancer, correlating with the metastatic potential of tumour cells. Angiopoietins are ligands for the endothelium-specific tyrosine kinase Tie2 receptor, which comprise 4 structurally related proteins, termed angiopoietin (Ang)-l, Ang-2, Ang-3 and Ang-4. The roles of Ang-1 and Ang-2 have recently been clarified as crucial in angiogenesis. In this report, we measured serum Ang-1 and Ang-2 levels in patients with cutaneous T-cell lymphoma (CTCL). Serum levels of Ang-2, but not Ang-1, in patients with Sézary syndrome were significantly higher than those in patch mycosis fungoides (MF), plaque/tumour MF, and healthy controls. In patients with CTCL, serum Ang-2 correlated with disease activity. Moreover, the numbers of Ang-2+ cells in lesional skin of CTCL were significantly larger than those in normal skin. These results suggest that Ang-2 may have important roles in the development of CTCL. [ABSTRACT FROM AUTHOR]

Objectives. Cathepsin V (CTSV) is a proteolytic enzyme potentially modulating angiogenic processes, collagen degradation and keratinocyte differentiation. We aimed to investigate the clinical association of serum CTSV levels and the mechanism by which CTSV expression is altered in SSc. Methods. Serum CTSV levels were determined by ELISA in 51 SSc and 18 healthy subjects. CTSV expression was evaluated by immunostaining in SSc and normal skin and by RT-real-time PCR in normal and SSc dermal fibroblasts, normal dermal fibroblasts treated with TGF-β1 or Fli1 siRNA and human dermal microvascular endothelial cells (ECs) treated with Fli1 siRNA. Results. Serum CTSV levels were significantly lower in dcSSc and lcSSc patients than in healthy controls. In early-stage dcSSc, serum CTSV levels were remarkably and uniformly decreased compared with healthy controls. The decrease in serum CTSV levels in mid- and late-stage dcSSc and in lcSSc was linked to the development of proliferative vasculopathy. CTSV expression was decreased in microvascular ECs, pericytes/vascular smooth muscle cells and keratinocytes of dcSSc and lcSSc skin and in dermal fibroblasts of dcSSc skin compared with control skin. Consistently, CTSV expression was decreased in cultured dermal fibroblasts from early-stage dcSSc. Furthermore, mRNA levels of the CTSV gene were significantly decreased in normal fibroblasts treated with TGF-β1 or Fli1 siRNA and in human dermal microvascular ECs treated with Fli1 siRNA. Conclusion. Loss of CTSV expression may contribute to the development of fibrosis, vasculopathy and the altered phenotype of keratinocytes in SSc. [ABSTRACT FROM AUTHOR]

The article presents a study which examined the soluble form of herpesvirus entry mediator (sHVEM) receptor expression and its ligand, lymphotoxin-like expression (LIGHT), in patients with cutaneous T-cell lymphoma (CTCL). The sHVEM, serum interleukin-2R, interleukin-4 and interleukin-10 and eosinophil levels of patients with mycosis fungigoides and Sézary were measured. A higher level of sVEM and LIGHT levels was recorded.