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Introduction: The broad and sustained efficacy of apremilast for psoriasis has been demonstrated in randomized and real-world observational studies. Data from Central and Eastern Europe (CEE) are lacking. Moreover, apremilast use in this region is limited by country-specific reimbursement criteria. This is the first study to report data on the real-world use of apremilast in the region. Methods: APPRECIATE (NCT02740218) was an observational, retrospective, cross-sectional study assessing psoriasis patients 6 (± 1) months after apremilast treatment initiation. The study aimed to describe the characteristics of patients with psoriasis receiving apremilast, estimate treatment outcomes, including Psoriasis Area Severity Index (PASI), Body Surface Area (BSA), and Dermatology Life Quality Index (DLQI), and assess dermatologists' and patients' perspectives on treatment using questionnaires including the Patient Benefit Index (PBI). Adverse event reports were taken from the medical records. Results: Fifty patients (Croatia: 25; Czech Republic: 20; Slovenia: 5) were enrolled. In patients continuing apremilast at 6 (± 1) months, mean (± SD) PASI score was reduced from 16.2 ± 8.7 points at treatment initiation to 3.1 ± 5.2 at 6 (± 1) months; BSA from 11.9% ± 10.3% to 0.8% ± 0.9%; DLQI from 13.7 ± 7.4 points to 1.6 ± 3.2. PASI 75 was reached by 81% of patients. Physicians reported that the overall treatment success fulfilled their expectations in more than two thirds of patients (68%). At least three-quarters of patients reported apremilast had a quite or very high benefit on the needs they identified as being most important. Apremilast was well tolerated; no serious or fatal adverse events were identified. Conclusion: Apremilast was effective in reducing skin involvement and improving quality of life in CEE patients having severe disease. Treatment satisfaction among physicians and patients was very high. These data add to the growing body of evidence showing consistent effectiveness of apremilast across the continuum of psoriasis disease severity and manifestations. Trial registration: ClinicalTrials.gov identifier, NCT02740218. [ABSTRACT FROM AUTHOR]

The occurrence of pruritus in psoriasis was previously underestimated but is a significant burden. Secukinumab (SEC), a monoclonal anti-interleukin-17A antibody, efficiently controls signs of psoriasis, but the effect on pruritus and cutaneous neuroanatomy remained unknown. The primary objective of this study (NCT02362789) was to evaluate the superiority of SEC treatment vs placebo on pruritus intensity (visual analogue scale; VAS). Furthermore, the treatment-dependent course of pruritus in association with absolute Psoriasis Area Severity Index (PASI) score, as well as cutaneous histopathology and neuroanatomy, was assessed. Open-label SEC 300 mg s.c. was administered regularly until week 16. Patients who reached a ≥ 98% PASI reduction (PASI ≥ 98) were randomized to receive either placebo or SEC up to week 32. Punch biopsies were collected from lesional psoriatic (baseline, weeks 16 and 32) and non-lesional (baseline) skin for histopathological and neuroanatomical analyses. VAS scores improved significantly after open-label SEC treatment but relapsed upon placebo (29.92 ± 33.8) compared with SEC (12.30 ± 22.6; p = 0.036). After SEC-dependent improvement in PASI, histopathology, marker expression and neuroanatomy, relapse was observed with treatment discontinuation in all parameters except neuroanatomy. SEC was superior to placebo by efficiently controlling reduced pruritus intensity, clinically normalizing skin lesions, and reversing histopathological abnormalities. The neuroanatomy recovered upon SEC and remained stable even after withdrawal.

Immunogenicity assessment is vital in clinical trials and is measured through a multi-tiered approach (screening, confirmatory and titer assays). However, recent studies have suggested that titer results could be reported from ADA signal-to-noise ratios (S/N ratios=sample mean signal/negative control mean signal). More data analysis using two clinical trials of adalimumab: SB5-1003 (single-dose, healthy participants) and SB5-4001 (multiple-dose, interchangeability study, patients with plaque psoriasis), therefore, is indispensable whether substituting ADA S/N ratio as an alternative way of reporting titer results has no impact on interpretation on clinical outcome. In this study, we demonstrated that there is a strong correlation between S/N ratios and titers and no impact on overall PK results. Nonetheless, sub-analyses with time or adalimumab level showed a change in the regression between S/N ratios and titers, leading to different titer values from the same S/N ratio. These data demonstrate that S/N ratios may fully replace titers in limited circumstances such as a biosimilar study which goal is to prove equivalence between the originator and candidate product, but need a caution in other cases., Competing Interests: Declarations Conflict of Interest The authors declare no conflicts of interest. Clinical Trial Registry [SB5-1003] 1.Trial registry name: clinicaltrials.gov2.Registration identification number: NCT045147963.The URL for the registry for the clinical trials performed: https://clinicaltrials.gov/study/NCT04514796?intr=SB5&rank=2.[SB5-4001] 1.Trial registry name: clinicaltrials.gov2.Registration identification number: NCT055100633.The URL for the registry for the clinical trials performed: https://clinicaltrials.gov/study/NCT05510063?intr=SB5&rank=4., (© 2024. The Author(s).)

Background: Psoriasis, characterized by chronic inflammation, is a persistent skin condition that is notoriously challenging to manage and prone to relapse. Despite significant advancements in its treatment, many adverse reactions still occur. Therefore, exploring the mechanisms behind the occurrence and development of psoriasis is extremely important., Methods: The weighted correlation network analysis (WGCNA) algorithm was used to identify phenotype-related genes in patients with psoriasis. We recruited clinical samples of patients with psoriasis, and used single-cell RNA sequencing (scRNA-seq) to visualize divergent genes and metabolisms of varied cells for the psoriasis. Various machine-learning methods were used to identify core genes, and molecular docking was used to analyze the stability of leptomycin B targeting pituitary tumor transforming 1 (PTTG1). Immunofluorescence (IHC) analysis, multiplex immunofluorescence (mIF) analysis, and quantitative reverse transcription polymerase chain reaction (qRT-PCR) were used to validate the results., Results: Our results identified 1391 genes associated with the phenotype in patients with psoriasis and highlighted the significant alterations in T-cell functionality observed in the disease by WGCNA. There were nine distinct cellular clusters in psoriasis analyzed with the aid of scRNA-seq data. Each subtype of cell exhibited distinct genetic profiles, functional roles, signaling mechanisms, and metabolic characteristics. Machine-learning methods further demonstrated the potential diagnostic value of T cell-derived PTTG1 and its relationship with T-cell exhaustion in psoriasis. Lastly, the leptomycin B was scrutinized and verified had high stability targeting PTTG1., Conclusions: This study elucidates the biological basis of psoriasis. At the same time, it was discovered that PTTG1 derived from exhausted T cells serves as a diagnostic biomarker for psoriasis. Leptomycin B could be a potential drug for targeted treatment of psoriasis on PTTG1., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Psoriasis is a prevalent, inflammatory skin disease without cure. Further research is required to unravel dysregulated processes and develop new therapeutic interventions. The lack of suitable in vivo and in vitro preclinical models is an impediment in the psoriasis research. Recently, the development of 3D skin models has progressed including replicas with disease-like features. To investigate the use of in vitro models as preclinical test tools, the study focused on treatment responses of 3D skin replicas. Cytokine-priming of skin organoids induced psoriatic features like inflammation, antimicrobial peptides (AMP), hyperproliferation and impaired differentiation. Topical application of dexamethasone (DEX) or celastrol (CEL), a natural anti-inflammatory compound reduced the secretion of pro-inflammatory cytokines. DEX and CEL decreased the gene expression of inflammatory mediators. DEX barely affected the psoriatic AMP transcription but CEL downregulated psoriasis-driven AMP genes. Subcutaneous application of adalimumab (ADM) or bimekizumab (BMM) showed anti-psoriatic effects via protein induction of the differentiation marker keratin-10. Dual blockage of TNF-α and IL-17A repressed the inflammatory psoriasis phenotype. BMM inhibited the psoriatic expression of AMP genes and induced KRT10 and cell-cell contact genes. The present in vitro model provides a 3D environment with in vivo-like cutaneous responses and represents a promising tool for preclinical investigations., Competing Interests: Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Objective: This post hoc analysis compared the immunogenicity of the biosimilar adalimumab-adbm (Cyltezo) with the adalimumab reference product (RP; Humira) across indications, including rheumatoid arthritis (RA), Crohn's disease (CD) and plaque psoriasis (PsO), and by patient sex in the VOLTAIRE trials programme., Methods: In each active-comparator randomised controlled trial (RCT), immunogenicity was assessed at various time points by the proportion of patients with antidrug antibodies (ADAs) and neutralising antibodies (nAbs), using acid dissociation followed by electrochemiluminescence assay. Assay sensitivity was 50 ng/mL, and drug tolerance was ≥30 µg/mL (free drug) at the low positive control level., Results: Minor differences in immunogenicity parameters (ADAs, ADA titres and nAbs) were evident between adalimumab-adbm and adalimumab RP across these three immune-mediated inflammatory diseases (IMIDs). The proportion of ADA-positive and nAb-positive patients increased from baseline over time in all three RCTs, as expected, and was similar in the RA and CD RCTs but with higher numbers of ADA-positive and nAb-positive patients reported in the PsO trial. Subgroup analysis by patient sex showed the same trend., Conclusions: Differences among the RCTs may partially be explained by concomitant background therapy (methotrexate) in the RA trial, stable doses of azathioprine, 6-mercaptopurine or methotrexate in 36% of patients with CD and absence of background therapy in the PsO RCT. The analyses further confirm the biosimilarity of adalimumab-adbm with the adalimumab RP across IMIDs and provide supporting evidence that adalimumab-adbm is an interchangeable biosimilar with consistent clinical results in patients originally treated with the RP., Trial Registration Numbers: VOLTAIRE-RA (NCT02137226; EudraCT 2012-002945-40); VOLTAIRE-CD (NCT02871635; EudraCT 2016-000612-14); VOLTAIRE-PsO (NCT02850965; EudraCT 2016-000613-79)., Competing Interests: Competing interests: VS reports consulting for AbbVie, Amgen, Aria, AstraZeneca, Bayer, Bioventus, BlackRock, BMS, Boehringer Ingelheim, Celltrion, ChemoCentryx, Equillium, Gilead, Genentech/Roche, Glenmark, GSK, Horizon, Inmedix, Janssen, Kiniksa, Kypha, Lilly, Merck, MiMedx, Novartis, Pfizer, Priovant, Regeneron, Rheos, R-Pharma, Samsung, Sandoz, Sanofi, Scipher, Setpoint, Sorrento, Spherix and Tonix. SB reports previous employment by Boehringer Ingelheim Pharmaceuticals. DM reports previous employment by Boehringer Ingelheim Pharmaceuticals., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Psoriasis, a chronic inflammatory skin disease, is associated with systemic complications that extend beyond cutaneous lesions, including cardiovascular risks and sexual dysfunction. Erectile dysfunction (ED) is notably more prevalent in male psoriasis patients, likely driven by both systemic inflammation and psychological stress. Adalimumab (ADA), a tumor necrosis factor-alpha (TNF-α) inhibitor, has been shown to effectively reduce psoriasis severity, but its effects on sexual and reproductive health remain underexplored. This study investigates the impact of ADA on erectile function, sperm parameters, and hormonal profiles in male psoriasis patients. This six-month prospective observational study included 33 biologic-naïve male patients aged 18-50 years with moderate-to-severe plaque psoriasis (Psoriasis Area and Severity Index [PASI] > 10). Patients received ADA according to standard clinical protocols. Erectile function was assessed using the International Index of Erectile Function (IIEF-5). Sperm parameters, including ejaculate volume, sperm concentration, total sperm count, motility, vitality, and morphology, were analyzed following World Health Organization (WHO) 2010 criteria. Hormonal profiles (testosterone, luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol, and prolactin) were measured via standardized assays. Statistical analyses were performed using paired t-tests or Wilcoxon signed-rank tests, with p-values < 0.05 considered significant. ADA significantly improved erectile function, as the mean IIEF-5 score increased from 21.3 ± 2.2 to 22.2 ± 1.9 (p = 0.03). The percentage of patients with ED decreased from 51.5% at baseline to 36.4% post-treatment (p < 0.001). Progressive sperm motility and vitality showed statistically significant improvement post-treatment (p = 0.02 and p = 0.04, respectively), while other sperm parameters remained unchanged. Total testosterone levels significantly increased from 3.4 ± 0.4 ng/ml to 3.5 ± 0.4 ng/ml (p = 0.02), while LH, FSH, estradiol, and prolactin levels showed no significant changes. The anti-inflammatory properties of adalimumab, through the inhibition of TNF-α, not only reduce psoriasis severity but also appear to exert positive effects on male sexual and reproductive health. Our study demonstrated significant improvements in erectile function, sperm motility, vitality, and testosterone levels in male psoriasis patients after adalimumab therapy. These findings suggest that beyond its role in controlling psoriatic skin lesions, adalimumab may help mitigate the systemic inflammatory burden that contributes to sexual dysfunction and impaired spermatogenesis. Future long-term studies are essential to further explore the sustained impact of TNF-α inhibition on male fertility and reproductive outcomes., Competing Interests: Declarations Consent of publication This paper is submitted with consent and knowledge of all co-authors. Informed consent All patients supplied consent with the awareness that this information might. be made publicly available, according to the consent for the publication of recognized patient. data or other identifying material that was received by the authors and included at the time of article submission to the journal. Competing interests The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Psoriasis, an autoimmune inflammatory disease characterized by hyperproliferation of keratinocytes, affects 0.2-4.8% of the global population. The disease manifests primarily as plaque psoriasis, causing chronic physical and psychological burdens. Although numerous treatments exist, there is ongoing exploration for novel therapies due to concerns about the toxicity, efficacy, and costs of current options. An A3 adenosine receptor (A3AR) agonist called Piclidenoson has been shown to reduce inflammation and could be used to treat moderate to severe psoriasis. This meta-analysis evaluates the safety and efficacy of Piclidenoson in psoriasis treatment. This meta-analysis was conducted accordance with the PRISMA guidelines and has been registered on PROSPERO (CRD42024566459). A comprehensive search on Cochrane CENTRAL, PubMed/MEDLINE, and Google Scholar was conducted up to July 2024. Included studies were randomized controlled trials (RCTs) involving Piclidenoson. Efficacy outcomes included PASI 75 and PGA 0 or 1, while safety outcomes included adverse events. Pooled outcomes were presented as odds ratio (OR) with 95% confidence intervals (CI). Statistical analysis employed the Mantel-Haenszel random-effects model, and heterogeneity was assessed using the I 2 and X 2 index. Three RCTs with 574 patients (313 Piclidenoson, 261 placebo) met the inclusion criteria. The pooled analysis showed no significant difference in achieving PASI 75 between Piclidenoson and placebo (OR: 1.62, 95% CI 0.70-3.75, P = 0.26, I 2  = 12%). However, Piclidenoson significantly improved PGA scores (OR: 2.74, 95% CI 1.22-6.16, P = 0.01, I²=0%). Safety assessment revealed no significant differences in adverse events, including nervous system, gastrointestinal, musculoskeletal, renal, and infections, compared to placebo. Piclidenoson demonstrates a significant improvement in PGA scores and a favorable safety profile, suggesting it could be a valuable addition to plaque-like psoriasis treatment. Further research with larger, longer-term RCTs is needed to confirm its efficacy and optimize clinical use., Competing Interests: Declarations Ethics approval and consent to participate Not applicable. Consent for publication Consent for publication is not applicable as this study involves publicly available data. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Janus kinase (JAK) inhibitors have gathered interest as treatments for several inflammatory and autoimmune diseases. The four first marketed inhibitors target JAK1, with varying selectivity towards other JAK family members, but none inhibit tyrosine kinase-2 (TYK2) at clinically relevant doses. TYK2 is required for the signaling of the interleukin (IL)-12 and IL-23 cytokines, which are key to the polarization of T H 1 and T H 17 cells, respectively; two cell subtypes that play major roles in inflammatory diseases. Herein, we report our effort towards the optimization of a potent and selective dual JAK1/TYK2 inhibitor series starting from a HTS hit. Structural information revealed vectors required to improve both JAK1 and TYK2 potency as well as selectivity towards JAK2. The potent inhibition of both JAK1 (3.5 nM) and TYK2 (5.7 nM) in biochemical assays by our optimized lead compound, as well as its notable selectivity against JAK2, were confirmed in cellular and whole blood assays. Inhibition of TYK2 by the lead compound was demonstrated by dose-dependent efficacy in an IL-23-induced psoriasis-like inflammation mouse model., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: All authors were employees of Galapagos at the time of the work. Ghjuvanni Coti, Line Oste, Steve De Vos, Miriam López-Ramos, René Galien, and Caroline Joannesse are employees of Galapagos. Raphaël Geney was an employee of Galapagos at the time of the study and is now an employee of Cabinet Nony. Céline Cottereaux, Isabelle Parent, Catherine Jagerschmidt and Béatrice Vayssiere were employees of Galapagos at the time of the study and are now employees of NovAliX. Oscar Mammoliti was an employee of Galapagos at the time of the study and is now an employee of Janssen. Christel Menet and Ann De Blieck were employees of Galapagos at the time of the study and are now employees of Confo Therapeutics. Javier Blanc was an employee of Galapagos at the time of the study and is now an employee of Farmacia Blanc CB. Koen Ostyn was an employee of Galapagos at the time of the study and is now an employee of FOD Financiën - SPF Finances. Adeline Palisse was an employee of Galapagos at the time of the study and is now an employee of Acerta Pharma B.V. Evelyne Quinton was an employee of Galapagos at the time of the study and is now an employee of AGC Pharma Chemicals Europe. Benoit Schmitt, Monica Borgonovi, and David Amantini were employees of Galapagos at the time of the study. Reginald Brys was an employee of Galapagos at the time of the study and is now an employee of Agomab Therapeutics. Kenji Shoji was an employee of Galapagos at the time of the study and is now an employee of Oncodesign Precision Medicine., (Copyright © 2024 Galapagos NV. Published by Elsevier Ltd.. All rights reserved.)

Psoriasis is a chronic inflammatory skin disease characterized by excessive proliferation of keratinocytes and infiltration of immune cells. Although psoriasis has entered the era of biological treatment, there is still a need to explore more effective therapeutic targets and drugs due to the presence of resistance and adverse reactions to biologics. Remetinostat, an HDAC inhibitor, can maintain its potency within the skin with minimal systemic effects, making it a promising topical medication for treating psoriasis. But its effectiveness in treating psoriasis has not been evaluated. In this study, the topical application of remetinostat significantly improved psoriasiform inflammation in an imiquimod-induced mice model by inhibiting CD86 expression of CD11C + I-A/I-E + dendritic cells (DCs) in the skin. Moreover, remetinostat could dampen the maturation and activation of bone marrow-derived DCs in vitro, as well as the expression of psoriasis-related inflammatory mediators by keratinocytes. In addition, remetinostat could promote keratinocyte differentiation without affecting its proliferation. Our findings demonstrate that remetinostat improves psoriasis by inhibiting the maturation and activation of DCs and the differentiation and inflammation of keratinocytes, which may facilitate the potential application of remetinostat in anti-psoriasis therapy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: The emergence of biological agents and small molecule drugs has revolutionized the treatment landscape for psoriasis, yet there remains a lack of systematic reviews elucidating the efficacy and safety of drugs for patients with psoriasis and mental disorders (MDs). The aim was to systemically evaluate the efficacy and safety of FDA-approved psoriasis drugs on MD symptoms and MD drugs on psoriasis symptoms., Methods: We conducted comprehensive literature searches of the PubMed, Embase, and Cochrane Library from inception to March 24, 2024, identifying 116 relevant studies for inclusion., Results: Our review encompasses 62 clinical trials and 54 case reports/series. Analyses of clinical trials revealed a positive impact of psoriasis drugs on MD, with notable exceptions including lithium and benzodiazepine receptor agonists, which exhibited adverse effects on psoriasis. Furthermore, analysis of case reports/series highlighted the efficacy of drugs such as apremilast, etanercept, infliximab, and secukinumab in ameliorating MD symptoms, contrasting with detrimental effects observed with methotrexate (MTX), cyclosporine, adalimumab, and secukinumab. Notably, tumor necrosis factor alpha (TNF-α) inhibitors and interleukin inhibitors demonstrated superior efficacy compared to conventional treatments. In the anxiety group, secukinumab showed the largest effective size as assessed by the Hospital Anxiety and Depression Scale - Anxiety (HADS-A) index; In the depression group, ixekizumab showed the largest effective size assessed by the 16-item Quick Inventory of Depressive Symptomology - Self-Report (QIDS-SR16) index., Limitations: The extracted data cannot be meta-analyzed, as the measurement scale is not uniform., Conclusions: This systematic review provides robust evidence regarding treatment options for individuals with psoriasis and MD, emphasizing the potential benefits of specific drugs in managing both conditions concurrently., Competing Interests: Declaration of competing interest The authors have no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Psoriasis is a prevalent chronic inflammatory and immunological disorder. Its lesions are present as scaly erythema or plaques. Disruptions in the body's immune system play a significant role in developing psoriasis. Recent evidence suggests a potential role of the gut microbiome in autoimmune diseases. Short-chain fatty acids (SCFAs) are the primary metabolites created by gut microbes and play a crucial fuction in autoimmunity. SCFAs act on various cells by mediating signaling to participate in host physiological and pathological processes. These processes encompass body metabolism, maintenance of intestinal barrier function, and immune system modulation. SCFAs can regulate immune cells to enhance the body's immune function, potentially influencing the prevention and treatment of psoriasis. However, the mechanisms underlying the role of SCFAs in psoriasis remain incompletely understood. This paper examines the relationship between SCFAs and psoriasis, elucidating how SCFAs influence the immune system, inflammatory response, and gut barrier in psoriasis. According to the study, in psoriasis, SCFAs have been shown to regulate neutrophils, macrophages, and dendritic cells in the adaptive immune system, as well as T and B cells in the innate immune system. Additionally, we explore the role of SCFAs in psoriasis by maintaining intestinal barrier function, restoring intestinal ecological homeostasis, and investigating the potential therapeutic benefits of SCFAs for psoriasis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Ethnopharmacological Relevance: Psoriasis, a widespread skin condition impacting over 100 million individuals globally, is characterised by uncontrolled hyperproliferation of keratinocytes, abnormal apoptosis, and excessive secretion of inflammatory cytokines and angiogenic factors. Traditional use of Alstonia scholaris (L.) R.Br., Wrightia tinctoria (Roxb.) R.Br. and Solanum xanthocarpum Schrad. & Wendl. in Ayurveda and Siddha medicinal systems have shown promising anti-inflammatory and wound-healing properties. However, underlying mechanisms of their phytoactivity in addressing psoriasis-like skin inflammation on human keratinocytes remain largely unexplored., Aim of the Study: The study was aimed to investigate anti-psoriatic potential of ethyl acetate and ethanolic extracts of A. scholaris, W. tinctoria and S. xanthocarpum in human keratinocyte cell line (HaCaT)., Material and Methods: Ethyl acetate and ethanolic extracts of A. scholaris (ASEA and ASE), W. tinctoria (WTEA and WTE) and S. xanthocarpum (SXEA and SXE) were first subjected to phytochemical screening through high-performance liquid chromatography (HPLC) using their marker compound loganin, kaempferol and chlorogenic acid, respectively. The proliferation inhibition efficiency of these extracts was measured using MTT assay on HaCaT cell line. Subsequently, the apoptotic effect of these extracts on HaCaT cell line was determined by JC-1 and Annexin V assays. Furthermore, IL-8 and RANTES levels were measured in TNF-alpha-induced HaCaT cell line post-treatment with these extracts to determine their anti-inflammatory properties., Results: ASEA, ASE, WTEA, WTE, SXEA and SXE significantly inhibited proliferation of keratinocytes (HaCaT cells) and resulted in the induction of apoptotic markers (mitochondrial membrane potential and phosphatidyl serine externalization). Additionally, pro-inflammatory markers (IL-8 and RANTES levels) were downregulated in HaCaT cells. The anti-proliferative effects were particularly distinct at higher concentrations (200 μg/mL), with inhibition rates reaching over 85% for W. tinctoria and S. xanthocarpum extracts. In apoptotic assays, notable increases in late apoptotic or necrotic cell populations and significant losses in mitochondrial membrane potential were observed. All extracts markedly reduced the secretion of inflammatory mediators IL-8 and RANTES., Conclusion: All three plants exerted an anti-psoriatic effect at the cellular level via multiple parameters (anti-proliferative, pro-apoptotic, anti-inflammatory effect). This study provides insight into the mechanism of action of ASEA, ASE, WTEA, WTE, SXEA and SXE and highlights their promising potential for development as herbal therapeutic agents for psoriasis. It emphasizes the need for further pharmacological evaluation and toxicological studies of these extracts., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Treating psoriasis presents a major clinical challenge because of the limitations associated with traditional topical glucocorticoid therapy. This study introduced a drug delivery system utilizing zinc-doped mesoporous silica nanoparticle (Zn-MSN) and microneedle (MN), designed to enhance drug utilization for prolonged anti-inflammatory and anti-itch effects. The MN system facilitated the transdermal delivery of betamethasone dipropionate (BD), allowing its slow release. The BD@Zn-MSN-MN system promoted the polarization of macrophages towards the anti-inflammatory M2 phenotype, achieving superior anti-inflammatory effects compared to the clinically used BD cream. Additionally, this study demonstrated that BD@Zn-MSN-MN could further alleviate itching in psoriasis-afflicted mice by decreasing the excitability of the transient receptor potential vanilloid V1 (TRPV1) ion channel positive neurons and reducing the release of calcitonin gene-related peptide (CGRP) in the dorsal root ganglion (DRG). These findings offer new insights and effective therapeutic options for the future design of transdermal drug delivery for psoriasis., Competing Interests: Declarations Ethics approval and consent to participate The animal experiments were approved by the Ethics Committee for Experimental Use of Animals of the Shanghai Jiao Tong University School of Medicine (approval code: #SYXK-2013-0050). Consent for publication All authors agree for publication. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Psoriasis is a common, chronic, recurrent, and inflammatory skin disease, which causes physical and psychological problems in patients and lacks effective and economic therapeutics. Herein, we designed Janus kinase (JAK) and histone deacetylase (HDAC) dual inhibitors as a new strategy for the treatment of psoriasis. In particular, compound 11i was identified with excellent inhibitory activity toward JAKs (JAK2 IC 50 = 0.49 nM) and HDACs (HDAC6 IC 50 = 12 nM). Moreover, it exhibited potent activities in inhibiting the proliferation of TNF-α-induced HaCAT cells and the production of nitric oxide. Importantly, compound 11i significantly ameliorated psoriasis-like skin lesions in an imiquimod-induced murine model with low toxicity, which was superior to JAK inhibitor momelotinib, HDAC inhibitor vorinostat, and their combination. This work provided a proof-of-concept for JAK/HDAC dual inhibitors as a promising strategy for the treatment of psoriasis.

Psoriasis is a chronic, inflammatory systemic condition mediated by T-lymphocyte activation. In patients with concomitant human immunodeficiency virus (HIV) infection, treatment of psoriasis remains a therapeutic challenge due to disruptions in the immune system targeting the quality and quantity of T-cell counts. Limited data exists on the knowledge of the utilization and tolerance of small-molecule and biologic therapies used for psoriasis in HIV-positive (HIV +) individuals. This study aims to provide an updated review detailing reports of efficacy and safety trends currently reported in the literature. A systematic review of PubMed, Cochrane, and Embase databases between January 2018 and April 2024 was performed, which included original investigations, reviews, case reports, and series of reported individuals with a prior diagnosis of psoriasis, and either a previous, or novel diagnosis of HIV during initiation of treatment. 19 articles with 24 cases were included in this review, including treatments apremilast (n = 5), adalimumab (n = 1), etanercept (n = 2), ustekinumab (n = 4), secukinumab (n = 5), ixekizumab (n = 2), brodalumab (n = 1), guselkumab (n = 1), and risankizumab (n = 3). Treatments were effective at improving cutaneous symptoms of psoriasis in all cases and 2 cases reported alleviation of psoriatic arthritis. Adverse events were seldom reported and were managed without interruption of medication. Higher evidence research is necessary to objectively determine the efficacy and safety profiles of these therapies in HIV + individuals., Competing Interests: Declarations Conflicts of interest The authors declare no competing interests. Ethical approval This is a systematic review study. No ethics approval is required., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Psoriasis is chronic immune-mediated inflammatory disorder characterized by various comorbidities, erythematous plaques with silvery scale which can lead to psoriatic arthritis. The phosphodiesterase 4 (PDE4) protein is a potential drug target to control Psoriasis. In the current study, pharmacophore-based virtual screening of Diversity library of ChemDiv database was first performed, and then the screened hits were docked to the active site of PDE4 to choose the best binding modes. Forty-six hits generated during the virtual screening were prepared and docked to the PDE4 receptor by SP docking module of glide. The binding affinities of the selected hits were calculated by molecular docking and based on the affinities, ten hits were selected for the bioactivity scores prediction and ADMET analysis. Based on the ADMET profiling, four hits D356-2630, C700-2058, G842-0420 and F403-0203 were processed to MD simulations for stability analysis. The outcomes showed that these compounds showed strong binding with proteins with better binding free energies. Based on the results of our study, we proposed that these hits can function as lead in the biological assays and in vitro studies are required to develop the novel drug candidates., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Alanzi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Psoriasis is a chronic, inflammatory skin disease characterized by a dysregulated immune response and systemic inflammation. Up to one-third of patients with psoriasis have psoriatic arthritis (PsA). Targeted treatment with antibodies neutralizing tumor necrosis factor can ameliorate both diseases. We here explored the impact of long-term infliximab treatment on the composition and activity status of circulating immune cells involved in chronic skin and joint inflammation. Immune cells were analyzed by multicolor flow cytometry. We measured markers of immune activation in peripheral blood mononuclear cell populations in 24 infliximab-treated patients with psoriasis/PsA compared to 32 healthy controls. We observed a significant decrease in the frequency of both peripheral natural killer (NK) cells and their subset CD56dimCD16+ NK cells in PsA compared to healthy controls and patients with psoriasis. The latter had a strong-positive correlation with psoriasis area severity index (PASI) in these patients, while CD56brightCD16- NK cells were negatively correlated with PASI. In addition, we observed an upregulation of CD69+ intermediate CD14+CD16+ and CD69+ classical CD14+CD16- monocytes in PsA and increased activity of CD38+ intermediate CD14+CD16+ monocytes in patients with psoriasis. Compared to healthy controls, psoriasis patients demonstrated shifts of the three B-cell subsets with a decrease in transitional CD27-CD38high B cells. Our exploratory study indicates a preserved pathophysiological process including continuous systemic inflammation despite clinical stability of the patients treated with infliximab., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Immunology.)

Introduction: Psoriasis and atopic dermatitis are chronic, immune-mediated skin disorders that are disqualifying for entrance into the military. Both conditions can cause difficulty wearing body armor and other protective equipment when poorly controlled, limiting a service member's ability to train and deploy worldwide. In addition, these conditions may be exacerbated by military service because of increased exposure to austere environments, extreme temperatures, stress, skin injury, bug bites, and vaccinations Service members have limited treatment options because of restrictions on systemic medications that can be used while deployed. Newer systemic medications-in particular, biologics and oral immunomodulators-have evolved to be both extremely effective and safe. We review more recent treatment options for psoriasis and atopic dermatitis in the context of DoD's regulations guiding entry and retention of personnel with psoriasis and eczema and make recommendations regarding updating DoD policy for systemic treatment options., Materials and Methods: A literature search was performed using PubMed, Embase, and Ovid with the last search done in the fall of 2023 from all years to date. These articles were further screened based on inclusion and exclusion criteria. In total, 25 articles were included in this review. An Internet search was also performed on the DoD's regulations guiding entry and retention of personnel with psoriasis and eczema. In addition, we examined medical requirements for deployment to the U.S. Central Command and U.S. European Command., Results: Currently, U.S. Central Command and U.S. European Command do not allow the use of medications with special storage and handling requirements on deployments. Newer biologics are safe and efficacious but require refrigeration, although other immunomodulators like deucravacitinib and apremilast are oral pills and do not have cold-storage requirements. However, the use of biologics in austere environments may be feasible because of increased intervals between dosing and the ability to store refrigerated medical supplies in most deployed environments. For military service members with psoriasis, risankizumab and deucravacitinib are excellent options given their favorable safety and efficacy profiles. Of the biologics available for atopic dermatitis, dupilumab is the safest and effective systemic medication available. The Janus kinase inhibitors have also demonstrated excellent efficacy in treating atopic dermatitis, but more safety data are needed because of potential adverse events to include heart-related events, blood clots, and cancers., Conclusions: Systemic treatments have evolved to become highly specific for both eczema and psoriasis. These newer biologics and immunomodulators may be compatible with use in the deployed setting, especially those that have long dosing intervals and proven efficacy and safety. Of the biologics, dupilumab and risankizumab offer the best efficacy, safety, and dosing intervals for atopic dermatitis and psoriasis, respectively. Deucravcitinib is a recently FDA-approved oral immunomodulator for psoriasis that has an excellent safety profile and efficacy. Allowing the use of these medications on deployments will enable more people with moderate to severe psoriasis and eczema to join and remain in the military while receiving effective treatment., (Published by Oxford University Press on behalf of the Association of Military Surgeons of the United States 2024. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Background: Psoriasis is an autoimmune skin condition characterized by hyperproliferation of keratinocytes and chronic immune responses. Gypenosides (Gyp) exhibits anti-proliferative and anti-inflammatory effects on different diseases. However, its functioning and mechanism of Gyp on psoriasis remains unknown., Objective: To explore the effect and mechanism of Gyp on psoriasis., Material and Methods: The impact and mechanism of Gyp on psoriasis in vitro and in vivo were probed through cell counting kit-8 (CCK-8), 5-ethynyl-2'-deoxyuridine (EdU) incorporation assay, reverse transcription quantitative polymerase chain reaction, hematoxylin and eosin staining, enzyme-linked immunosorbent serologic assay, immunofluorescence, and Western Blotting assays., Results: Gyp inhibited cell proliferation and the release of inflammatory cytokinesin interleukin (IL-22)-induced spontaneously transformed human aneuploid immortal keratinocyte cell line (HaCaT). In addition, Gyp demonstrated enhancement in erythema and scaling as well as reductions in the thickness of epidermal layers, release of inflammatory factors, and Ki-67 (a nuclear protein) level in imiquimod (IMQ)-induced mice. Mechanistically, Gyp upregulated nuclear factor erythroid 2-related factor 2 (Nrf-2) expression and diminished the level of p-p65/p65 and p-STAT3/STAT3 in skin tissues from IMQ-induced mice and IL-22-induced HaCaT cells, which were reversed with the application of ML385, an inhibitor of Nrf2. In addition, the administration of ML385 reversed decrease in cell viability and reduced the expressions of IL-1β, IL-6, and tumor necrosis factor-α (TNF-α) in IL-22-induced HaCaT cells caused by Gyp., Conclusion: In summary, Gyp reduced excessive cell growth and inflammation in psoriasis by suppressing nuclear factor kappa B (NF-κB) and signal transducer and activator of transcription 3 (STAT3) through activation of Nrf2.

Purpose: Biological treatment has been a game changer in the management of moderate-to-severe psoriasis. In Denmark, biological treatment for psoriasis is registered in two data sources. We aimed to describe the utilization of biologics for psoriasis in Denmark using data from both data sources separately., Methods: We used data from two different nationwide Danish data sources: The healthcare registries and the clinical quality database, Dermbio. Utilization patterns were described by three different parameters: (1) distribution of drugs used in the first treatment episodes, (2) treatment cascade on a population level, and (3) drug survival using Kaplan Meier (KM) analysis and the proportion of patients covered (PPC) method., Results: From January 1, 2011, to December 31, 2018, we found 1878 users of biologics in the healthcare registries and 2264 in Dermbio. Adalimumab, ustekinumab, and secukinumab were the most common first-choice treatments throughout the study period. According to the healthcare registries, it was most common to have more than one treatment episode with the same drug. In Dermbio, most were registered to have only one observable treatment episode overall in the study period. Ustekinumab showed the longest drug survival in both databases. Drug survival was longer for all biologics in Dermbio than in the healthcare registries., Conclusion: Adalimumab, ustekinumab, and secukinumab were the most common first-choice treatments in Denmark. Overall, ustekinumab showed the longest drug survival. We observed important differences in treatment cascades and drug survival between Dermbio and the healthcare registries, which should be considered when using these data sources to perform drug utilization studies on biologics., (© 2024 The Author(s). Pharmacoepidemiology and Drug Safety published by John Wiley & Sons Ltd.)

This systematic literature review examines the relationship between psoriasis and trace metals to elucidate the pathogenesis of this condition, and to explore their potential use as a new route of treatment. Searches were primarily conducted in three databases: PubMed, Scopus, and Embase. The initial search resulted in over 100 articles which were manually assessed by the researchers to determine relevancy. Articles were only included if they were published within the last 12 years and were held to the standards of Boote and Biele's Literature Review Rubric to assess their quality. Of the relevant articles included in this study, the following three elements were largely discussed: calcium, magnesium, and zinc. Although not a trace metal, the macromolecule, calcium, was found to regulate the differentiation and proliferation of cells involved in the pathogenesis of psoriasis. Magnesium is thought to have an indirect relationship with psoriasis due to its role in Vitamin D absorption. Additionally, the zinc ion protects against oxidative stress, which is theorized as a mediator of the inflammatory response central to the pathogenesis of psoriasis. Many studies also investigated the serum levels of these elements to see if they were correlated with the severity of the condition. The serum levels of both calcium and zinc were found to have a negative correlation with the amount of surface area involved during a plaque psoriasis flare. These results indicate a potential benefit from evaluating the serum levels of these key modulators in patients. The lab values would indicate any deficiencies or imbalances, which can assist in a physician's ability to determine an individualized and targeted treatment course. Findings from this review consolidate the information currently available, and support the idea that psoriasis is influenced by trace metals. While there is still limited discussion on the evaluation of this relationship, the reviews findings demonstrate that additional comprehensive research would be warranted., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objectives: To evaluate health-related quality of life perceived by patients with the most prevalent immune-mediated inflammatory diseases in Spain: inflammatory bowel disease (IBD), psoriasis (Ps), psoriatic arthritis (AP), rheumatoid arthritis (RA), and spondyloarthropathies (SpAs), and to determine the factors that influence patient quality of life., Methods: The SACVINFA study (SA = satisfaction, CV = quality of life, IN = immune-mediated, FA = pharmacy) consisted of an observational study conducted in 4 hospitals in the Community of Madrid. A cross-sectional analysis was made of adult patients diagnosed with an immune-mediated inflammatory disease who attended the Pharmacy Service. Quality of life was assessed using the EQ-5D-5L questionnaire (mobility, self-care, usual activities, pain/discomfort and anxiety/depression) and specific questionnaires: SIBDQ-9, DLQI, PsAQoL, QoL-RA and ASQoL., Results: A total of 578 patients were analyzed (inflammatory bowel disease = 25.3%; psoriasis = 19.7%; spondyloarthropathies = 18.7%; rheumatoid arthritis = 18.5%; psoriatic arthritis = 17.8%). The mean age (SD) was 49.8 (12.3) years and 50.7% were male. The average score (SD) for the global EQ-5D- 5 L was 0.771 (0.2) and the mean (SD) visual analogue scale score was 71.5 (20.0). Type of immune-mediated inflammatory diseases was associated with differences in quality of life showing psoriasis and inflammatory bowel disease higher values of EQ-5D-5L than psoriatic arthritis, rheumatoid arthritis and spondyloarthropathies, p < 0,05 in all comparisons. Patients with RA, IBD, and Ps achieved 70% of the maximum score, while patients with PsA and SpAs did not reach 50% of the maximum possible score. Female gender, a state of moderate/severe disease severity, an older age and a higher number of previous treatments were correlated with worse quality of life. Conversely, persistence to current treatment correlated with better quality of life., Conclusions: Patients with immune-mediated inflammatory diseases have markedly affected quality of life, mainly in the pain/discomfort dimension, especially in those immune-mediated inflammatory diseases with a rheumatological component., (Copyright © 2024 Sociedad Española de Farmacia Hospitalaria (S.E.F.H). Publicado por Elsevier España, S.L.U. All rights reserved.)

Introduction: Psoriasis and psoriatic arthritis (PsA) are interrelated autoimmune conditions sharing similar genetic and immunological pathways. PsA often develops within 10 years of psoriasis onset, though it may precede cutaneous symptoms in some patients. Effective management of these conditions requires a multidisciplinary approach to address skin, bone, joint, and vascular manifestations., Areas Covered: The review summarizes the current pharmacotherapies and to provide treatment guidelines for managing cutaneous psoriasis and PsA in psoriatic disease., Expert Opinion: The management for mild psoriasis and mild PsA flare-ups can be addressed with topical treatments and with NSAIDs or intra-articular glucocorticoid injections. For more persistent or severe cases, systemic treatments with oral small molecules (Methotrexate, Apremilast, Janus kinase inhibitors) or with biologics (TNF inhibitors, IL-17 inhibitors, IL-23 inhibitors, CTLA-4 Ig) are effective in managing both psoriasis and PsA. With many treatment options, providers can tailor management, which considers patient disease severity, preference, comorbidities, and other factors. Early detection and a multidisciplinary management strategy can optimize patient quality of life and improve health outcomes.

The aim of this study was to investigate the impact of using microneedle patches in addition to topical therapy for the treatment of psoriasis. Using continuous liquid interface production (CLIP) 3D printing we manufactured round microneedle array patches (MAPs) with a diameter of 14 mm. Needle geometries were varied from square pyramidal, conical, and obelisk, with varied needle lengths of 400 µm, 600 µm, 800 µm, or 1000 µm. MAPs were characterized for force to fracture, skin penetration, skin damage, as well as their ability to deliver a novel oleogel-based corticosteroid (betamethasone dipropionate (BDP) formulation into ex-vivo porcine skin. We found that the obelisk shaped MAPs are more durable compared to the conical and square pyramidal-shaped MAPs. When the obelisk shaped MAPs were used in combination with the oleogel-based BDP formulation, the amount of BDP penetrating the skin was significantly increased with greater needle lengths., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Inflammatory diseases that are driven by several pro-inflammatory cytokines has resulted in in the development of targeted therapies across different disease settings. Interleukin (IL)-36 cytokines have been implicated in several inflammatory diseases. In this review we describe the scientific evidence surrounding the use of the IL-36 receptor (IL-36R)-targeting antibody, spesolimab, in IL-36-mediated skin diseases: generalized pustular psoriasis (GPP), palmoplantar pustulosis (PPP), hidradenitis suppurativa, and Netherton syndrome (NS). Spesolimab, a high affinity, specific, humanized, antagonistic immunoglobulin G1 antibody, targets the IL-36R at a binding site distinct from its agonists, IL-36α/β/γ, and at least one endogenous antagonist, IL-36R antagonist. In vitro and in vivo data for spesolimab show effective inhibition of IL-36R-mediated signaling pathways, and six Phase I studies in healthy volunteers presented a favorable safety and pharmacokinetic (PK) profile, leading to the development of a clinical trial program to evaluate spesolimab in the treatment of IL-36R-mediated diseases. Six studies (including an expanded access program) have evaluated the efficacy, safety, PKs, and pharmacogenomics of spesolimab in patients with GPP flares. Spesolimab treatment of GPP flares resulted in rapid and sustained improvements in pustular and skin clearance, and clinically significant improvements in patient-reported symptoms and quality of life. Spesolimab also significantly reduces the risk of GPP flares and flare occurrence, preventing disease worsening and has a favorable safety profile. There have been three trials of spesolimab in PPP; further evaluation is needed to better define those patients who might benefit from the treatment. A trial of spesolimab in NS is ongoing, while other spesolimab trials suggest that IL-36 may only play a secondary role in the pathogenesis of atopic dermatitis. In conclusion, research into spesolimab has provided much needed insight into the role of IL-36 in the human immune system and the mechanism behind IL-36-mediated inflammatory diseases. Spesolimab provides an efficacious targeted treatment for GPP, a disease with a high unmet medical need., (© 2024 The Author(s). The Journal of Dermatology published by John Wiley & Sons Australia, Ltd on behalf of Japanese Dermatological Association.)

Bimekizumab treatment has demonstrated significant improvements in clinical outcomes in patients with moderate to severe plaque psoriasis; however, studies so far have focused on predominantly White patient populations from North America and Europe, with one smaller study in a Japanese population. Here, clinical responses, safety, and tolerability of bimekizumab treatment in Korean patients are reported. Korean patients with moderate to severe plaque psoriasis were randomized to bimekizumab 320 mg every 4 weeks (Q4W) or placebo Q4W to week 16. Co-primary efficacy end points were achievement of ≥90% improvement from baseline in the Psoriasis Area and Severity Index (PASI 90) and Investigator's Global Assessment score of 0/1 (clear/almost clear) at week 16. Secondary efficacy end points included achievement of PASI 75 at week 4 and Dermatology Life Quality Index 0/1 at week 16. Safety outcomes were also assessed. Statistical analysis of the co-primary efficacy end points was performed using a type I error rate, at a two-sided α level of 0.05. Overall, 47 Korean patients were randomized to treatment (bimekizumab: 32, placebo: 15). At week 16, bimekizumab-treated patients had significantly higher clinical responses versus placebo-treated patients (PASI 90: 81.3% vs. 0%; IGA 0/1: 87.5% vs. 0%, p < 0.001 for both). Bimekizumab showed a rapid onset of clinical response, with 75.0% of patients achieving PASI 75 by week 4 (0% in placebo patients [nominal p < 0.001]). A higher proportion of bimekizumab-treated patients achieved DLQI 0/1 at week 16 (46.9% vs. 6.7% in placebo patients, nominal p = 0.007), indicating greater improvements in health-related quality of life (HRQoL) following bimekizumab treatment. Bimekizumab was well-tolerated in Korean patients, with no new safety signals identified. Treatment with bimekizumab led to rapid improvements in clinical responses and HRQoL versus placebo in Korean patients, consistent with responses in global populations. These findings suggest that bimekizumab is an effective and well-tolerated treatment option in Korean patients with psoriasis., (© 2024 The Author(s). The Journal of Dermatology published by John Wiley & Sons Australia, Ltd on behalf of Japanese Dermatological Association.)

Background: Psoriasis is a chronic inflammatory skin disease. To date, there are no serum biomarkers for psoriasis that have been validated to diagnose or treat psoriasis., Methods: Peptidase inhibitor 3 (PI3) levels in serum were measured using chemiluminescence immunoassay (CLIA) in two independent cohorts including healthy controls (HC) and patients diagnosed with chronic urticaria (CU), chronic eczema (CE), systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), psoriatic arthritis (PsA), or psoriasis vulgaris (PV). Receiver operating characteristic (ROC) curve analysis determined the diagnostic performance of PI3 in patients with psoriasis. The correlation between PI3 levels and the Psoriasis Area Severity Index (PASI) score was analyzed using the Spearman correlation method. Additionally, the study evaluated PI3 expression and treatment response of PV patients 12 weeks before and after topical treatment with calcipotriol betamethasone and calcipotriol ointment (T#1) or topical therapy plus PSORI-CM01 granules (T#2)., Results: In cohort #1, PI3 levels effectively discriminate PV patients from HC and CU patients, with AUCs of 0.909 and 0.840, respectively. In cohort #2, AUCs for detecting PV patients among HC, CU, CE, SLE, and RA patients were 0.940, 0.926, 0.802, 0.989, and 0.951, respectively. For PsA patients, AUCs were 0.989, 0.986, 0.910, 1.000, and 0.984 compared to HC, CU, CE, SLE, and RA patients, respectively. In both cohorts, PI3 levels correlated significantly with PASI scores in PV patients (cohort #1, r = 0.433; cohort #2, r = 0.634) and PsA patients (cohort #2, r = 0.718). Moreover, univariate logistic regression analyses revealed that PV patients with higher PI3 expression had a significantly higher risk of treatment resistance, with an odds ratio of 3.45 [95% confidence interval (CI) 1.54, 7.74, p = 0.003]. Finally, PI3 levels decreased nearly 35-fold more in the responder than in the non-responder group before and after treatment., Conclusions: Serological PI3 is a reliable biomarker for PV diagnosis and may have the potential to predict and monitor the progression of PV before and after treatment. Key Points • This study validated PI3's diagnostic performance in two independent psoriasis cohorts using CLIA. • PI3 expression is significantly correlated with the psoriasis severity and with patients who benefited from the treatments. • Serological PI3 is a reliable biomarker for psoriasis diagnosis and may have the potential to monitor the psoriasis progression with and without treatments., (© 2024. The Author(s), under exclusive licence to International League of Associations for Rheumatology (ILAR).)

Background: For patients with psoriasis, discontinuation of biologics following remission has become more common in daily practice., Objective: We aimed to identify predictors and construct a predictive model for time to relapse following withdrawal from biologics., Methods: This 12-year, multicenter, observational cohort study was performed in six dermatology centers between February 2011 and February 2024. We identified biological treatment episodes in patients with moderate-to-severe psoriasis and included only treatment episodes in which a clinical response (≥ 50% reduction in Psoriasis Area and Severity Index score [PASI 50] from baseline) was achieved and the patient withdrew from biological therapy with a well-controlled status (PASI < 10 and ≥ 50% improvement in PASI from baseline). The primary outcome was time to relapse, which was defined as the period from the last biologic administration to relapse. An extended multivariate Cox proportional hazards analysis (Prentice-Williams-Peterson Gap time model) was used to predict relapse and generate a predictive model., Results: This study screened 1613 biological treatment episodes, and 991 treatment episodes were enrolled. The time to relapse decreased significantly as the number of previous withdrawals from biological treatment increased (p < 0.001). Similarly, the time to relapse decreased significantly as the number of previous biologics used increased (p < 0.001). The maximum PASI improvement during biological treatment decreased and the PASI score at withdrawal of biological treatment increased in parallel as the number of prior withdrawals from biologics increased. The time to relapse following withdrawal was longest for interleukin (IL)-23 inhibitors (IL-23i), followed by the IL-12/23i, IL-17 inhibitors (IL-17i), and tumor necrosis factor-α inhibitors. After adjustment, multivariate Cox regression identified the following significant predictors of relapse following withdrawal: the mechanisms of action of biologics (hazard ratio [HR] for IL-17i vs IL-12/23i, 1.59; HR for IL-23i vs IL-12/23i, 0.60), number of previous withdrawals from biological treatment (HR 1.23; 95% confidence interval [CI] 1.13‒1.33), time to achieve PASI 50 (HR 1.01; 95% CI 1.00‒1.02), maximum PASI improvement on biologics (HR 0.98; 95% CI 0.98‒0.99), and PASI at the end of therapy (HR 1.03; 95% CI 1.01‒1.05). The model had good predictive and discriminative ability., Conclusions: These results have the potential to help physicians and patients make individualized treatment decisions; information on the risk of relapse of psoriasis at specific timepoints following the withdrawal of biologics is particularly valuable for patients considering discontinuation of biologics or as-needed biologic therapy. However, the benefit and risk of repeated withdrawals of biologics should be carefully weighed, as the treatment efficacy and duration of remission decline as the number of withdrawals increases., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background and Objective: Erosions of the skin and mucous membranes with epidermal dysmaturation are a known side effect of cytostatic chemotherapy regimens and can also be observed during low-dose methotrexate (MTX) therapy. The study aimed to delineate the clinical and histopathological alterations., Patients and Methods: A database search of the archive for dermatopathology was conducted, identifying 22 patients who developed epidermal dysmaturation on low-dose MTX. Clinical and laboratory changes, along with an array of histologic parameters were analyzed and statistically evaluated using SPSS., Results: Patients were predominantly female with a mean age of 69.1 years. The main indications were psoriasis vulgaris and rheumatoid arthritis. Clinically, patients mostly presented erosive plaques at the injection site, on mucosal surfaces, and disseminated lesions. Most patients showed normal laboratory values. Histopathologically, key findings included enlarged keratinocytes with pale cytoplasm and enlarged nuclei with prominent nucleoli, along with the degeneration of the basal layer. Consistent observations in the dermal compartment included infiltration of neutrophilic granulocytes, lymphocytes, and histiocytes., Conclusions: This study proposes clinicopathological criteria for the diagnosis of MTX-associated skin toxicity, aiming to increase awareness among clinicians and pathologists for early diagnosis. Early recognition can prevent potentially life-threatening progression., (© 2024 The Author(s). Journal der Deutschen Dermatologischen Gesellschaft published by John Wiley & Sons Ltd on behalf of Deutsche Dermatologische Gesellschaft.)

Psoriasis, a chronic inflammatory skin disease, is characterized by complex immune dysregulation and oxidative stress responses. The neonatal Fc receptor (FcRn) plays a crucial role in the development of autoimmune diseases. Analysis of clinical psoriasis samples demonstrated a negative correlation between FcRn expression in skin lesions and disease severity. However, the role of FcRn in this process remains unclear. This study aimed to investigate the involvement of FcRn in the pathogenesis and progression of psoriasis. In an imiquimod (IMQ)-induced psoriasis-like mouse model, FcRn expression was significantly decreased in the lesional skin, and transcriptome sequencing of the skin revealed activation of the ferroptosis pathway in psoriasis. This led to the hypothesis that FcRn could potentially regulate ferroptosis via the signal transducer and activating transcription factor 3 (STAT3)/solute carrier family 7 member 11 (SLC7A11) axis. Further experiments showed exacerbated psoriasis-like lesional skin and ferroptosis in FcRn-knockout mice, whereas intervention with the ferroptosis inhibitor Fer-1 or STAT3 inhibitor Stattic alleviated these symptoms. Critical binding sites for the transcription factor STAT3 were identified in the SLC7A11 promoter region at positions -1185 and -564 using the luciferase reporter assays and chromatin immunoprecipitation. The administration of 1,4-naphthoquinone (NQ), an FcRn agonist, effectively alleviated psoriasis-like skin lesions by inhibiting ferroptosis. This study highlights the molecular mechanisms of action of FcRn in psoriasis and provides an experimental basis for the development of novel therapeutic strategies targeting FcRn., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Psoriasis, a chronic inflammatory skin disease, presents unique challenges when co-occurring with HIV. Tildrakizumab, an IL-23p19 inhibitor, has demonstrated efficacy in treating moderate-to-severe psoriasis. This retrospective case series reports three individuals living with HIV and psoriasis treated with tildrakizumab. Clinical outcomes, including Psoriasis Area and Severity Index (PASI) and HIV viral load, were recorded over a year. All three patients achieved significant clinical improvements with tildrakizumab, with PASI scores improving by over 95%. No adverse effects were reported, and HIV viral loads remained undetectable. Tildrakizumab appears to be a safe and effective treatment option for psoriasis in individuals living with HIV, providing significant benefits without compromising HIV control., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Psoriasis (PSO) poses a global health threat. The current research challenge in PSO is relapse. Liquiritin (LIQ), a major active compound from Glycyrrhiza inflata Batalin, has multiple pharmacological properties, including anti-inflammatory and anti-proliferative. Nonetheless, the precise mechanisms underlying LIQ's therapeutic actions in PSO and prevention abilities remain elusive., Purpose: The present study aimed to delve into the potential to treat and prevent PSO and the mechanism of LIQ., Methods: The anti-inflammatory and anti-proliferative effects of LIQ were studied in vitro with the HaCaT cell line. Then, Transcriptional analysis and bioinformatic analysis were used to determine the internal associations of the target set. Subsequently, functional experiment, luciferase report assay, ChIP-PCR, and immunohistochemical validation of clinical samples were performed to investigate the mechanism of LIQ. Finally, the anti-psoriatic effects and prevention abilities of LIQ were verified in vivo with imiquimod (IMQ)-induced PSO-like mouse models., Results: Here, we identified differentially expressed genes in LIQ-stimulated HaCaT cells and Retinol-Binding Protein 3 (RBP3) as the core target, whereas YY1 was a predicted upstream transcription factor of RBP3. The YY1/RBP3 axis was obviously altered after administering LIQ at optimal doses of 20 μM in vitro and 100 µg/ml in vivo. LIQ can significantly inhibit the progression of PSO in vivo. Notably, LIQ also prevented the relapse of psoriatic lesions induced by the second round of low-dose IMQ. Mechanistically, we observed that LIQ could increase the promotion of YY1 for RBP3 by enhancing the binding affinity between them., Conclusion: These findings revealed that the YY1/RBP3 axis is a potential psoriatic target, and LIQ is a promising and innovative therapeutic candidate for the treatment and prevention of PSO., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Background: Generalized pustular psoriasis (GPP) is a rare, potentially life-threatening skin disease often requiring long-term therapy. We aimed to evaluate the use of Interleukin (IL)-17A inhibitors (secukinumab and ixekizumab) in GPP patients over 96 weeks., Methods: We retrospectively analyzed a case series of 18 patients with GPP who received secukinumab (n = 13) and ixekizumab (n = 5) therapy with a 96-week follow-up period. The primary effectiveness analysis included determining the percentage of patients who achieved ≥90% or 100% improvement in the Generalized Pustular Psoriasis Area and Severity Index (GPPASI) score. Adherence was captured using the medication possession ratio (MPR)., Results: Using the as-observed (AO) method, 87% and 67% of patients treated with secukinumab or ixekizumab achieved GPPASI 90 and 100 responses, respectively. At Week 96, the mean GPPASI improvements from baseline GPPASI were 96.3% (95% CI: 0.91-1.01) using the AO method. After Week 48, 14 patients tapered (n = 8) or terminated (n = 6) the treatment. High-adherence therapy (MPR ≥ 80%) was significantly superior to the low-adherence group in the rate of patients achieving a GPPASI 100 response (AO, 100% vs. 38%, P < 0.05). By Week 96, 5 (27.8%) patients had new GPP flares, and 4 (80%) were in the low-adherence group. No new safety signals occurred., Conclusion: IL-17A inhibitors led to effective and sustained improvement in GPP patients, and high-adherence therapy had long-term positive effects on skin clearance. Given its relapsing nature, improving compliance is beneficial for long-term clinical management., (© 2024 the International Society of Dermatology.)

Background Psoriasis is a chronic, inflammatory, systemic disease with predominant manifestations in the skin and joints impairing patient's quality of life. A proportion of patients have frequent severe disease exacerbations requiring repeated systemic treatments. There is a scarcity of literature evaluating the role of systemic maintenance therapy in psoriasis patients in preventing such frequent disease flares. Objective To evaluate the efficacy and safety of weekend cyclosporine treatment (WCT) as maintenance therapy in moderate to severe chronic plaque psoriasis patients for the prevention of frequent disease exacerbations. Methods In this retrospective cohort study, 22 psoriasis patients with a history of frequent disease exacerbations (≥ 3 in the last 1 year) who were administered WCT (group A) were compared with the same number of matched patients (age and gender) not on WCT or any systemic maintenance therapy (group B). Results Four patients (18.2%) in group A had disease exacerbations which was significantly lower (p = 0.00, Fisher's exact test) as compared to 21 patients (95.5%) in group B during the study period. Also, patients in group A had significantly lower number of overall exacerbations [mean ± SD: 0.23 ± 0.53 vs 2.95 ± 1.43) p = 0.00, Mann-Whitney U test] as compared to group B. Four (9.1%) patients in group A encountered adverse effects (acneiform eruptions - two, mild gingival hyperplasia - one, myalgia - one) as compared to three (acneiform eruptions - two, headache - one) in group B (p = 1.00). Conclusion WCT significantly reduced the number of disease exacerbations and is a safe and effective mode of maintenance therapy in such subset of psoriasis patients.

Background: Evidence describing the types and annual costs of biological treatments for psoriasis in Latin America is scarce. This study aimed to estimate the frequency of use and costs of biologic therapy for psoriasis in Colombia in 2019., Methods: This secondary data analysis uses the International Classification of Diseases terms associated with psoriasis, excluding those related to psoriatic arthritis, based on data from the registry of the Colombian Ministry of Health. We estimated the prevalence of psoriasis per 100,000 inhabitants; then, we retrieved the frequency of use of biologic therapy in patients with psoriasis and estimated the cost per year of each and overall therapies in 2019 in US dollars (USD)., Results: There were 100,823 patients with psoriasis in Colombia in 2019, which amounts to a prevalence of 0.2% in the general population. Of those patients, 4.9% received biologic therapy, most frequently males (60%). The most commonly used biological therapies for psoriasis in Colombia in 2019 were ustekinumab (35.2%), with an annual cost per patient of $12,880 USD; adalimumab (26%), with a yearly cost per patient of $7130 USD; and secukinumab (19.8%), with an annual cost per patient of $6825 USD., Conclusion: This is the first study to describe the use and cost of biological therapy for psoriasis in Colombia. It provides valuable cost-awareness information for the Colombian health system., (© 2024 The Author(s). International Journal of Dermatology published by Wiley Periodicals LLC on behalf of the International Society of Dermatology.)

Background: Brodalumab, a fully human monoclonal immunoglobulin IgG2 antibody that binds the human interleukin 17 receptor subunit A, is available for the treatment of moderate-to-severe plaque psoriasis in Europe since September 2017, but so far there are only a few studies on its use in real-world conditions., Objectives: To assess the management of moderate-to-severe psoriasis with brodalumab 210 mg in daily practice after 12 and 52 weeks (W). In addition, patient profiles and treatment pathways are described., Methods: LIBERO is a prospective, multicenter, non-interventional study including adult patients with plaque psoriasis treated with brodalumab 210 mg., Results: In total, 638 patients (65% male, mean age: 49.3 ± 14.4 years) from 148 sites in Germany were enrolled. The majority suffered from severe (51.1%) or very severe (13.1%) psoriasis according to physician global assessment (PGA0-5). When starting with brodalumab, 58.5% were biologic naïve and 41.5% were previously treated with another biologic, mainly adalimumab (18.5%) and secukinumab (17.9%). About 74.0% of patients met the primary endpoint of an absolute PASI ≤3 at ~W12 (n = 618, LOCF). The mean PASI was reduced significantly as of ~W2 from 17.2 (±11.7) to 9.7 (±8.8) and improved further to 3.3 (±6.3) at ~W12 (p < 0.001). At ~W52 85.5% of patients reached a PGA0/1-response (primary endpoint) and 54.1% patients were assessed as completely clear (PGA0) (both n = 399, as observed). Effectiveness of brodalumab was confirmed in relevant subgroup analysis by previous treatment regimen. Most frequently reported adverse events were nasopharyngitis (4.6%), psoriasis (4.6%) and arthralgia (4.1%), new safety signals were not detected., Conclusions: This representative, non-interventional study confirms the short- and long-term effectiveness and safety profile of brodalumab in the management of psoriasis in daily practice as well as in relevant treatment pathways., (© 2024 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.)

A 10-year-old boy presented with persistent genital erythematous plaques unresponsive to traditional topical treatments. Apremilast, an underexplored option in pediatric cases, was initiated and resulted in a significant reduction in pruritus and resolution of the lesions. This case provides insight into the potential efficacy of apremilast in refractory pediatric inverse psoriasis and underscores the necessity for further research in this specific population., (© 2024 Wiley Periodicals LLC.)

Background: In comparison with TNF-α inhibitors, anti-IL-17A agents are considered to have a lower risk of active tuberculosis (TB) or latent TB infection (LTBI) reactivation., Methods: In this study, we aimed to evaluate the TB infection status and serial QuantiFERON-TB-Gold in tube test (QFT) results of psoriasis patients using IL-17 inhibitors (secukinumab [SEC] and ixekizumab [IXE]) in a real-world setting from a tuberculosis-endemic country. Patients who used an anti-IL-17 agent for at least 3 months in our follow-up were included in the study. Patients' clinical and demographic features, baseline QFT results and latest QFT results (if any), and TB infection status were noted from the past medical records., Results: A total of 717 patients, of whom 333 (46.4%) were female, were included in the study. The cumulative exposure time to an anti-IL-17 agent was 14,147 patient-months, 9743 patient-months for SEC and 4404 patient-months for IXE. Also, 459 (SEC = 305/IXE = 154) patients used an anti-IL-17 agent for ≥ 12 months. Of these, 125 had positive baseline QFT results. In all, 334 had negative baseline QFT results. The latest QFT result of 309 was also negative (persistent seronegative group). During follow-up, the QFT results of 10 patients changed from negative to positive (positive seroconversion group). Seven of them were using SEC and three were using IXE, respectively. No case of active TB infection was detected., Conclusion: In our study, the positive seroconversion rate of 10/334 seems high, but this did not translate to active disease. However, closer monitoring may be required, especially in patients with advanced age, the presence of PsA, long disease duration and long anti-IL-17 treatment duration., (© 2024 The Author(s). Australasian Journal of Dermatology published by John Wiley & Sons Australia, Ltd on behalf of Australasian College of Dermatologists.)

Psoriasis is a skin disorder characterized by impaired epidermal differentiation that is regularly treated by systemic drugs with undesirable side effects. Based on its anti-inflammatory, antiproliferative and anti-melanoma attributes, the fungal metabolite kojic acid represents an attractive candidate for anti-psoriatic research. The present work aims to investigate an efficient topical bio-friendly vesicular system loaded with kojic acid isolated from Aspergillus oryzae as an alternative way for the management of psoriasis to avoid systemic toxicity. Kojic acid-loaded spanlastics were prepared by ethanol injection technique, employing span 60 along with brij 35 and cremophor rh40 as edge activators, with the complete in vitro characterization of the developed nanoplatform. The selected formulation displayed a spherical morphology, an optimum particle size of 234.2 ± 1.65 nm, high entrapment efficiency (87.4% ± 0.84%) and significant sustained drug release compared with the drug solution. In vivo studies highlighted the superior relief of psoriasis symptoms and the ability to maintain healthy skin with the least changes in mRNA expression of inflammatory cytokines, achieved by the developed nanoplatform compared to kojic acid solution. Moreover, the in vivo histopathological studies confirmed the safety of the topically applied spanlastics. In addition, the molecular mechanism was approached through in vitro assessment of cathepsin S and PDE-4 inhibitory activities and in silico investigation of kojic acid docking in several anti-psoriatic drug targets. Our results suggest that a topically applied vesicular system loaded with kojic acid could lead to an expansion in the dermo-cosmetic use of kojic acid as a natural bio-friendly alternative for systemic anti-psoriatic drugs., (© 2024 Deutsche Pharmazeutische Gesellschaft.)

Objective: Inhibitors of the interleukin 13 (IL-13) pathway, such as dupilumab, are licensed for atopic dermatitis and asthma. Adverse events resembling psoriatic disease after dupilumab initiation have been reported, but evidence is limited to case reports with uncertain causality. We aimed to investigate whether genetically mimicked IL-13 inhibition (IL-13i) is associated with risk of psoriatic arthritis (PsA) and psoriasis., Methods: We instrumented IL-13i using a protein-coding variant in the IL13 gene, rs20541, that is associated with circulating eosinophil count (biomarker of IL-13i) at genome-wide significance in a study of 563,946 individuals. Outcome genetic data were taken from studies of PsA, psoriasis, and related spondyloarthritis traits in up to 10,588 cases and 209,287 controls. Colocalization analysis was performed to examine genetic confounding. We additionally used circulating IgE as a biomarker to test whether associations were replicated, both in the test and in an independent genetic dataset. We also replicated analyses using individual-level data from the UK Biobank., Results: Genetically proxied IL-13i was associated with increased risk of PsA (odds ratio [OR] 37.39; 95% confidence interval [95% CI] 11.52-121.34; P = 1.64 × 10 -9 ) and psoriasis (OR 20.08; 95% CI 4.38-92.01; P = 1.12 × 10 -4 ). No consistent associations were found for Crohn disease, ulcerative colitis, ankylosing spondylitis, or iritis. Colocalization showed no strong evidence of genetic confounding for psoriatic disease. Results were replicated using circulating IgE for the exposure, using independent outcome data and using individual-level data., Conclusion: We provide supportive genetic evidence that IL-13i is linked to increased risk of PsA and psoriasis. Physicians prescribing IL-13 inhibitors should be vigilant for these adverse events., (© 2024 The Author(s). Arthritis & Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Background: Scarce data related to the drug survival of biologic agents in psoriasis patients aged ≥65 years is available., Objectives: To evaluate the drug survival of interleukin (IL)-23 or the IL-17 inhibitors approved for the treatment of moderate-to-severe psoriasis in elderly patients (aged ≥65 years), compared with younger adult patients (aged <65 years), and to identify clinical predictors that can influence the drug survival., Methods: This retrospective multicentric cohort study included adult patients with moderate-to-severe psoriasis, dissecting two-patient subcohorts based on age: elderly versus younger adults. Kaplan-Meier estimator and proportional hazard Cox regression models were used for drug survival analysis., Results: We included 4178 patients and 4866 treatment courses; 934 were elderly (1072 treatment courses), and 3244 were younger patients (3794 treatment courses). Drug survival, considering all causes of interruption, was higher in patients aged <65 years than in elderly patients overall (log-rank p < 0.006). This difference was significant for treatment courses involving IL-23 inhibitors (p < 0.001) but not for those with IL-17 inhibitors (p = 0.2). According to both uni- and multi-variable models, elder age was associated with an increased risk of treatment discontinuation (univariable analysis: HR: 1.229, 95% CI 1.062-1.422; p < 0.006; multivariable analysis: HR: 1.199, 95% CI 1.010-1.422; p = 0.0377). Anti-IL-23 agents were associated with a reduced likelihood of treatment discontinuation after adjusting for other variables (HR: 0.520, 95% CI 0.368-0.735; p < 0.001). Being previously treated with IL-17 inhibitors increased the probability of discontinuation., Conclusions: Elderly patients with psoriasis have an increased risk of biologic treatment discontinuation compared with younger adult patients, particularly, if being treated with IL-23 inhibitors. However, in stratified analyses conducted in elderly patients, IL-23 inhibitors showed higher drug survival rates than IL-17 inhibitors., (© 2024 European Academy of Dermatology and Venereology.)

Following the market authorization of interleukin (IL)-17 inhibitors, a growing number of cases of IL-17 inhibitor-induced paradoxical psoriasis (PsO) have been reported. Our objectives were to present two cases of IL-17 inhibitor-induced paradoxical PsO and to systematically review the literature for similar cases, summarizing and presenting the relevant data. A systematic literature review of previously presented cases of paradoxical PsO induced by IL-17 inhibitors was conducted. We presented two patients with axial spondyloarthritis (axSpA) and paradoxical PsO induced by secukinumab (SEC). One patient's psoriatic lesions responded well to adjuvant topical treatment, while the other patient required a combination of topical treatment and cyclosporine Α for successful treatment. SEC was continued in both cases. We also identified 35 patients with IL-17 inhibitor-induced paradoxical PsO in the literature review. The most frequent types of paradoxical PsO were palmoplantar pustular and plaque PsO, while the median latency period was 11 weeks. Approximately one-third of patients continued IL-17 inhibitor treatment with adjunctive therapy, primarily topical, which produced satisfactory results in most patients. Almost two-thirds of the patients discontinued the IL-17 inhibitor, with the majority of patients switching to another biological agent with a different mechanism of action or initiating other systemic antipsoriatic treatments, resulting in mainly satisfactory outcomes. Therefore, paradoxical PsO induced by IL-17 inhibitors appears to respond well in both patients who continue IL-17 inhibitors with adjunctive treatment and those who discontinue IL-17 inhibitors while switching to a different class of biological agent or initiating other systemic antipsoriatic treatments., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The definition of paradoxical psoriasis (PP) encompasses 2 main scenarios, namely, (i) new-onset psoriasis in patients treated for a different disease and (ii) worsening as well as phenotypical change of pre-existing psoriasis. Originally restricted to the appearance of an untoward psoriasiform reaction under TNF inhibitors, the term has gained new meaning, with the progressive observation of psoriasis-like eruptions also with other medications. Although the conceptual framework of PP has expanded, a molecular and clinicotherapeutic classification is still lacking. In addition, a certain degree of confusion surrounds the correct terminology to indicate these eruptions. In this paper, evidence on the epidemiology, clinical features, pathogenesis, and treatment of PP is reviewed, providing a perspective on possible pathogenesis-driven therapeutic approaches., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

The investigation of gene regulation therapeutics for the treatment of skin-related diseases is rarely explored in part due to inefficient systemic delivery. In this study, a bottlebrush polymer-antisense oligonucleotide (ASO) conjugate, termed pacDNA, designed to target IL-17 receptor A (IL-17RA), which is involved in psoriasis pathogenesis is presented. Systemic administration of pacDNA led to its accumulation in epidermis, dermis, and hypodermis of mouse skin, reduced IL-17RA gene expression in skin, and significantly reversed the development of imiquimod (IMQ)-induced psoriasis in a mouse model. These findings highlight the potential of the pacDNA as a promising nanoconstruct for systemic oligonucleotide delivery to the skin and for treating psoriasis and other skin-related disorders through systemic administration., (© 2024 The Author(s). Small published by Wiley‐VCH GmbH.)

Background: The efficacy and safety of secukinumab in psoriasis patients has been demonstrated in randomized controlled clinical trials., Objectives: The authors aimed to evaluate the efficacy and safety of secukinumab in plaque psoriasis patients followed in our clinic., Methods: Data from 101 plaque psoriasis patients who received at least 16 weeks of secukinumab treatment between June 2018 and June 2023 were retrospectively analyzed., Results: Fifty-three (53%) of the patients were bionaive. PASI-75, -90, -100 response rates were 72%, 50%, 30% respectively at week 16 in all patients. PASI-75 and -90 responses were higher in naive patients at weeks 16 and 28 (p < 0.001, p < 0.001, p < 0.01, p = 0.01, respectively). The percentage of patients with PASI ≤ 1, ≤ 3, ≤ 5 were 50%, 77%, and 92%, respectively at week 16. They were higher in the naive group than in nonnaive group at weeks 16 and 28 (p = 0.02, p < 0.01, p = 0.05, p = 0.07, p < 0.01, p = 0.03, respectively). At week 52, PASI-75, -90, -100 responses were significantly lower in smoking patients (p = 0.04, p = 0.03, p < 0.01, respectively). The mean duration of secukinumab treatment was 19.80 ± 12.76 months. Secukinumab was discontinued 14 (26.4%) naive patients and 28 (58.3%) nonnaive patients at one occasion during treatment (p < 0.001). The most common adverse event in patients was mucocutaneous candida infection (8%). No hepatitis B or C reactivation and no active or reactivation tuberculosis were observed in any of the patients during the follow-up period., Study Limitations: This is a single-center retrospective study with relatively few patients including only the Turkish population., Conclusion: Secukinumab seems to be effective in plaque psoriasis, particularly in bionaive and non-smokers. Moreover, it is safe in patients with inactive hepatitis or tuberculosis., (Copyright © 2024 Sociedade Brasileira de Dermatologia. Published by Elsevier España, S.L.U. All rights reserved.)

Background: Managing psoriasis (PsO) and its comorbidities, particularly psoriatic arthritis, often involves using interleukin (IL)-23 and IL-12/23 inhibitors. However, the comparative risk of these treatments still needs to be explored., Objective: This study evaluates the risk of developing psoriatic arthritis in patients treated with IL-23 inhibitors compared to IL-12/23 inhibitors., Methods: This retrospective cohort study utilized data from the TriNetX, including adult patients diagnosed with PsO. Patients with IL-23 or IL-12/23 inhibitors treatment were included and propensity score matched. The primary outcome was the incidence of psoriatic arthritis (PsA), analyzed using a Cox regression hazard model and Kaplan-Meier estimates., Results: The study included matched cohorts of patients treated with IL-23 inhibitors (n = 2273) and IL-12/23 inhibitors (n = 2995). Cox regression analysis revealed no significant difference in the cumulative incidence of PsA between the IL-23i and IL-12/23i cohorts (P = .812). Kaplan-Meier estimates confirmed similar cumulative incidences of arthropathic PsO in both cohorts over the study period., Limitation: Long-term follow-up studies are required to understand more of the effects of these interleukin inhibitors., Conclusion: No significant difference but a numerically lower risk of psoriatic arthritis in PsO patients treated with IL-23 inhibitors than with IL-12/23 inhibitors was found, underscoring their comparable efficacy in PsO management and follow-up., Competing Interests: Conflicts of interest None disclosed., (Copyright © 2024 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: The advent of novel biologics has led to an increase in biologic-switching as patients and clinicians pursue improved clinical outcomes. However, guidance on treatment sequencing in an Australian setting is sparse. This study examines the patterns of care across two tertiary centres in Australia and characterizes the factors contributing to biologic-switching., Methods: A retrospective study of patients who attended the outpatient Dermatology biologic clinics across two tertiary hospitals was conducted. Data on treatment sequencing and patients' PASI at every visit from April 2006 to December 2020 were collected. Patterns of biologic-switching were examined. The speed of treatment response for each biologic was determined by the time to achieve PASI-90 and -100 for each treatment course., Results: A total of 440 treatment courses were analysed. Ustekinumab and adalimumab were the most frequently prescribed first-line biologics. The highest proportion of biologic-switching was observed among patients on TNF-α inhibitors (63.8%). After 2015, more patients were prescribed IL-12/23 and IL-17 inhibitors in favour of TNF-α inhibitors. IL-17 inhibitors demonstrated the most rapid treatment response and low PASI scores relative to other biologics. Patients who did not switch biologics had lower rates of psoriatic arthritis and lower BMI, compared to patients who switched biologics. The median PASI on discontinuation generally exceeded 3.0, while on continuation, it was less than 1.2, reflecting patients' and clinicians' thresholds for biologic-switching., Conclusions: This study demonstrates an increased uptake of more novel biologics as they become available, due to improved safety profiles and clinical outcomes., (© 2024 The Author(s). Australasian Journal of Dermatology published by John Wiley & Sons Australia, Ltd on behalf of Australasian College of Dermatologists.)

Background: Psoriasis is a common immune-related chronic inflammatory skin disease, often accompanied by significant itching, and once diseased, the course of the disease lasts for most of the lifetime. Tanshinol (TAN) is an active ingredient of Salvia miltiorrhiza, which possesses pharmacological effects such as anti-inflammatory and antioxidant properties. However, the effects of TAN on psoriasis have not been widely reported. Therefore, the aim of this study was to investigate the therapeutic effects and mechanisms of TAN in psoriasis., Methods: An imiquimod (IMQ)-induced psoriasis mouse model was constructed and treated with different doses of TAN to observe the changes in skin lesion phenotype, macrophage polarization, inflammation and Notch signaling pathway in mice. Further removal of macrophages or inhibition or activation of Notch signaling pathway was performed to examine the changes in skin lesion phenotype, macrophage polarization, inflammation and Notch signaling pathway in mice. In addition, in vitro experiments verified that TAN regulates RAW264.7 macrophage polarization and cytokine secretion through the Notch pathway., Results: The results showed that TAN alleviated IMQ-induced skin lesions and pathological phenotypes in psoriasis mice and inhibited Notch signaling pathway and M1-type macrophage polarization. Moreover, macrophage clearance and Notch signaling pathway activation inhibited the effect of TAN on psoriasis. Further in vitro experiments showed that Notch agonists reversed the effects of TAN on macrophage polarization and inflammatory cytokines., Conclusions: Collectively, these findings suggest that TAN may exert a therapeutic effect on psoriasis by inhibiting the Notch signaling pathway and thus M1-type macrophage polarization., (© 2024. The Author(s).)

There are comorbidities and complications in atopic dermatitis and psoriasis that often occur after the appearance of skin inflammation. Statistically, data show that patients with psoriasis and atopic dermatitis have a shorter life expectancy than patients without psoriatic dermatitis, due to the occurrence of arteriosclerosis, myocardial infarction, and cerebral infarction. Many types of skin inflammation are treated with various antibody preparations, and marked improvement in patients' quality of life can be achieved. The next theme is to understand the pathogenesis of arteriosclerosis, myocardial infarction, stroke, and other complications associated with dermatitis and to find treatments and drugs to reduce their occurrence. The skin, a crucial immune organ, generates large amounts of inflammatory cytokines in response to various stimuli, leading to systemic inflammation and potential damage to internal organs. The link between inflammatory skin conditions like psoriasis and atopic dermatitis with serious health complications such as vascular disorders and systemic amyloidosis has been increasingly recognized. In psoriasis, biological treatments targeting Interleukin (IL)-17A, a key cytokine, have shown promise in reducing cardiovascular risks. Recent developments include treatments that target both IL-17A and IL-17F in the psoriasis field, though each cytokine's impact on internal organ damage is still under debate. Among visceral complications secondary to dermatitis, systemic amyloidosis and atherosclerosis have been reported to be controlled by suppressing IL-17 in the early stages of dermatitis. Still, it remains unclear whether suppressing IL-17 prevents organ damage in the late stages of persistent severe dermatitis. A study using a long-lasting dermatitis mouse model that overexpressed human caspase-1 in keratinocytes (Kcasp1Tg) investigated the effects of deleting IL-17A and IL-17F on visceral complications. Cross-mating Kcasp1Tg with IL-17A-, IL-17F-, and IL-17AF-deficient mice assessed the skin and visceral organs histologically, and RT-PCR analysis of aortic sclerosis markers was performed. Despite less improvement in dermatitis, deletion of IL-17A in Kcasp1Tg mice showed promising results in reducing multiple organ amyloidosis. On the other hand, the effect was observed in both IL-17A and IL-17F deleted mice for aortic sclerosis. The inhibition of IL-17A and IL-17F was suggested to reduce the risk of developing comorbidities in internal organs. IL-17A and IL-17F were found to act similarly or produce very different results, depending on the organ.