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Takeda announced positive topline results for the Phase 3, randomized, multicenter, double-blind study comparing zasocitinib (TAK-279), an investigational, next-generation, highly selective and potent oral tyrosine kinase 2 (TYK2) inhibitor, to deucravacitinib in adults with moderate-to-severe plaque psoriasis (PsO).

In the LATITUDE Atlas (TAK-279-PsO-3004) head-to-head study, zasocitinib demonstrated statistical superiority over deucravacitinib for the primary endpoint, Psoriasis Area and Severity Index (PASI) 100 response rate at week 16. The study also demonstrated statistical superiority over deucravacitinib for all key secondary endpoints, including PASI 90 response and Static Physician's Global Assessment (sPGA) 0 at week 16. Zasocitinib was generally well tolerated with a consistent safety and tolerability profile and no new safety signals identified.

These head-to-head results build on the strong efficacy seen across our Phase 3 program, with more than 35% of zasocitinib-treated patients achieving complete skin clearance (PASI 100) at week 16 – more than 2.5 times the response rate for deucravacitinib – and separation from the deucravacitinib curve as early as week 8, together, these findings reinforce the promise of zasocitinib to deliver rapid and durable skin clearance in a convenient once-daily pill and demonstrate the transformative potential of highly selective and potent TYK2 inhibition for patients suffering with plaque psoriasis.

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Background:
Multiphoton tomography equipped with fluorescence lifetime imaging (MPT-FLIM) is a novel noninvasive imaging technique for analyzing morphological and metabolic states of skin diseases at a subcellular resolution. The present study is the first to establish MPT-FLIM as an imaging modality to monitor treatment response in psoriasis during topical anti-inflammatory therapy.

Materials and Methods:
Patients with psoriasis treated with topical calcipotriol/ betamethasone dipropionate (C/B) or a calcipotriol derivative (C/-) formulation were recruited and monitored using MPT-FLIM. Imaging was performed at baseline on day 0, and during treatment on days 3 and 28.

Results:
A total of six patients prescribed C/B, six patients prescribed C/- and four healthy controls were recruited. Characteristic histological features were visualized, including acanthosis, parakeratosis, papillomatosis, and thinning of the granular layer. There was a strong correlation between clinical, multiphoton tomographic, and pathophysiological improvement during treatment. Assessment of subclinical metabolic changes was a predictive parameter for treatment outcome. Detection of fluorescence signals from drug components allowed for tracking of drug distribution in intra- and intercellular spaces.

Conclusion:
MPT-FLIM proved to be a suitable tool for monitoring treatment response in psoriasis patients and tracking drug delivery. It could be a potential method for monitoring other inflammatory skin diseases during treatment to adjust therapy on an individual level.

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Background:
Biologic therapy in psoriasis raises concerns regarding COVID-19 infection risk and vaccine response, yet real-world data remain limited.

Objective:
To evaluate COVID-19 infection rates, clinical severity, and vaccination response among biologic-treated patients with psoriasis during the COVID-19 pandemic.

Methods:
This cohort study included 12,306 patients with psoriasis followed at a tertiary medical center between March 2020 and May 2023. Primary outcomes included estimated SARS-CoV-2 infection rates, hospitalization, ICU admission, mortality, and a composite severe COVID-19 outcome (hospitalization, ICU admission, or death).

Results:
Based on national seroprevalence-adjusted rates, infection occurred in 673 of 962 biologic-treated patients (70.0%) and 7657 of 11,344 nonbiologic patients (67.5%) (p = 0.18). Hospitalization was more frequent among biologic-treated patients (45.2% vs 25.1%; p < 0.001), while ICU admission rates were comparable (2.6% vs 2.0%; p = 0.41). Mortality was significantly lower in the biologic group (6.3% vs 12.1%; p < 0.001).

Conclusions:
Biologic therapy in psoriasis was not associated with increased susceptibility to SARS-CoV-2 infection or impaired vaccine response.

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The functional significance of RNA modifications, specifically N7-methylguanosine (m7G), in inflammatory conditions such as psoriasis remains not fully elucidated. This study demonstrates that methyltransferase-like 1 (METTL1), an m7G methyltransferase, is significantly upregulated in epidermal keratinocytes of human psoriatic lesions and imiquimod (IMQ)-induced murine models.

Utilizing mice with an inducible keratinocyte-specific Mettl1 deletion (Mettl1fl/flKrt14-CreERT2), the research reveals significantly attenuated psoriasiform inflammation and decreased neutrophil infiltration relative to Mettl1fl/fl counterparts. Mechanistically, METTL1 drives inflammation by augmenting Bdkrb1 mRNA stability through m7G modification. This stabilization leads to elevated bradykinin receptor B1 (BDKRB1) protein expression, which activates the p38 mitogen-activated protein kinase (MAPK) pathway in keratinocytes, promoting the secretion of key proinflammatory C-X-C motif chemokine ligand (CXCL) chemokines and robust neutrophil chemotaxis. Crucially, both in vivo genetic BDKRB1 overexpression and pharmacological BDKRB1 activation successfully rescue the attenuated inflammatory phenotype in Mettl1-deficient mice, firmly validating this specific signaling cascade.

Conversely, pharmacological inhibition of the METTL1–BDKRB1 axis effectively mitigates psoriasiform inflammation. Collectively, these data establish that METTL1 modulates psoriasis by fostering p38-dependent chemokine production and neutrophil recruitment, identifying the METTL1–BDKRB1 axis as a novel therapeutic target.

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The BE SHINING study by Cai et al., the phase 3 trial to evaluate bimekizumab in Chinese patients with psoriasis, represents the largest clinical trial of bimekizumab conducted in an Asian population to date. Asian patients with psoriasis have been reported to exhibit distinct pathophysiologic and phenotypic features from those observed in Western populations. This study provides essential validation that the clinical outcomes established in global trials are reproducible within the context of Asian patients.

Indeed, the dual inhibition of IL-17A and IL-17F by bimekizumab yields a profound clinical response in this Chinese cohort. In the present trial, 74.0% of patients achieved PASI 75 as early as week 4, and notably, 94.0% and 65.0% reached PASI 90 and PASI 100, respectively, at week 16. Overall, these findings confirm that the high-level efficacy of bimekizumab established in global clinical trials is consistently maintained in this regional setting.

Regarding safety, bimekizumab demonstrated a tolerable safety profile in the BE SHINING study, with no new safety signals identified. Consistent with global clinical trials, upper respiratory tract infections were the most common treatment-emergent adverse events (TEAEs). Interestingly, no cases of oral candidiasis were reported, similar to findings from a Korean study, but contrasting with data from global and Japanese populations where oral candidiasis was a relatively common TEAE. As the authors suggested, a small sample size or a short observation period may partially explain this discrepancy. However, the comparable size (n = 133) to the Japanese cohort (n = 108) and the typical early onset of candidiasis during the first 16 weeks of treatment in global trials suggest that population-specific factors, such as characteristic oral microbiomes or distinct immunologic profiles, may play an important role. These findings highlight the need for real-world data on bimekizumab in Asian populations and further mechanistic studies to clarify the factors driving this phenomenon.

Another notable safety finding was the higher frequency of hepatic events compared with global clinical trials. Given that the rate of hepatic events was similar between the bimekizumab and placebo groups and considering the pharmacologic profile of IL-17 inhibitors, these events are unlikely to be directly related to the drug. Instead, they may reflect the high baseline prevalence of hepatic disorders (21.1%) in this population, which the authors suggest is likely associated with metabolic dysfunction–associated steatotic liver disease (MASLD). Clinicians may nevertheless consider monitoring liver function in patients with psoriasis at high risk of hepatic events (i.e. underlying MASLD, obesity or excessive alcohol consumption) while receiving bimekizumab when clinically indicated, not to detect drug-related hepatotoxicity but to assess underlying liver disease. Patients should also be encouraged to adopt lifestyle modifications, even when psoriasis is well controlled with bimekizumab.

In summary, this study reaffirms that bimekizumab delivers a rapid and profound clinical response, including high rates of PASI 90 and PASI 100 in Chinese patients with psoriasis, consistent with previous global trials. Although distinct patterns in the rates of oral candidiasis and hepatic events were observed in this regional cohort, these findings do not alter the overall favourable benefit–risk profile of bimekizumab. Further real-world studies are warranted to confirm these observations and to clarify the population-specific factors that may influence clinical outcomes in Asian patients.

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Background and Aim:
Psoriasis and inflammatory bowel disease are characterized by relapsing episodes of immune-mediated, chronic inflammation and frequently co-occur. However, the potential causal relationship between these two conditions and their shared pathogenesis remains unclear. We aimed to explore the pathogenesis and association between psoriasis and inflammatory bowel disease.

Methods:
We performed longitudinal cohort analyses using the UK Biobank and additionally incorporated three independent external datasets—the International IBD Genetics Consortium GWAS dataset, the FinnGen psoriasis GWAS dataset, and the plasma proteome dataset reported by Sun et al. to conduct Mendelian randomization and proteomic mediation analyses, thereby investigating the association between inflammatory bowel disease and psoriasis and exploring potential underlying mechanisms.

Results:
Inflammatory bowel disease increased psoriasis risk in the UK Biobank cohort, as indicated by the Cox model and Mendelian randomization analysis. Smoking, body mass index, and air pollution were identified as risk factors for psoriasis in inflammatory bowel disease patients. In addition, multiple intermediary proteins and their activation pathways were implicated. The epidermal growth factor receptor substrate 15-like 1 was demonstrated as a mediating protein for Crohn's disease and ulcerative colitis in the incidence of psoriasis. Enrichment analysis indicated that the downregulation and signaling of the epidermal growth factor receptor were potential biological mechanisms contributing to the causal relationships between genetic effects and the development of psoriasis and inflammatory bowel disease.

Conclusion:
The epidermal growth factor receptor pathway is a potential mechanism in inflammatory bowel disease-induced psoriasis. This study may inform the clinical management of psoriasis and inflammatory bowel disease.

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Background:
High-impact site plaque psoriasis is difficult to treat. Icotrokinra, an oral peptide with high specificity for the interleukin (IL)-23 receptor, demonstrated significantly higher rates of high-impact site psoriasis clearance, versus placebo, with no safety signals, through Week (W)16.

Objectives:
Report clinical response rates and safety through 1 year of icotrokinra treatment in participants with high-impact site plaque psoriasis.

Methods:
Participants (≥12 years of age; psoriasis body surface area ≥1%; Investigator's Global Assessment [IGA] ≥2) with at least moderate scalp, genital or hand/foot psoriasis were randomized (2:1) to once-daily icotrokinra 200 mg (N = 208) or placebo (N = 103), with placebo-to-icotrokinra transition at W16 (N = 92). Rates (using nonresponder imputation) of achieving clear/almost clear (0/1) or clear (0) overall skin (IGA), genital (static Physician's Global Assessment of genitalia [sPGA-G]), hand/foot (hf-PGA) psoriasis and absent/very mild (0/1) or absent (0) scalp psoriasis (scalp-specific-IGA [ss-IGA]), modified Nail Psoriasis Severity Index (mNAPSI) percent improvement and safety were assessed through W52.

Results:
Eighty-eight per cent (275/311) of participants completed treatment through W52. In icotrokinra-randomized participants, response rates increased through W24 and were durable through W52 for overall psoriasis clearance (IGA 0/1 range: 67%–70%) and across high-impact sites (ss-IGA 0/1: 72%–78%; sPGA-G 0/1: 85%–90%; hf-PGA 0/1: 54%–62%); responses were consistent among placebo-randomized participants after transitioning to icotrokinra. High proportions of icotrokinra-randomized participants achieved complete clearance during W24–52 (IGA 0: 44%–51%; ss-IGA 0: 57%–66%; sPGA-G 0: 73%–84%; hf-PGA 0: 44%–58%). Mean mNAPSI improvement increased from W16 (33%) to W52 (62%). Exposure-adjusted rates of participants with ≥1 adverse event (AE) or serious AE through W16 were similar between icotrokinra and placebo, with no increase in AE rates or occurrence of a safety signal through W52.

Conclusions:
Icotrokinra demonstrated high and durable rates of psoriasis clearance across high-impact sites, with a favourable safety profile, through 1 year.

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Psoriasis is an immune-mediated skin disease in which genetic and environmental factors have a significant role. Olive oil with antioxidant properties is an effective adjunct treatment for skin diseases. Furthermore, ozone by introducing O2 into the bloodstream controls the response of cell-mediated immunity and leads to improve disease. So, the aim of this study was to evaluate the efficacy of ozone therapy in the treatment of Psoriasis.

Topical therapy of lesions of a man suffering from psoriasis was carried out using ozonate olive oil two times a day and ozone sauna once a week during a month. Patient showed considerable improvement after about twenty days.

As the itching and silvery-white scaling decreased, the lesions began to resolve after three weeks. Furthermore, no recurrence was noted after 3 months of follow-up.

It is suggested that ozone therapy, in appropriate formulations and in controlled cases, has a role in the treatment of patients with psoriasis by inhibiting the inflammatory pathways and prompting regenerative characteristics, without significant adverse effects and the necessity for systemic pharmacological agents. So, more studies on a greater population are needed to confirm this finding.

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This review provides a comprehensive overview of macrophage heterogeneity, polarisation dynamics, metabolic reprogramming and multicellular interactions of macrophages in psoriasis.

We discuss how single-cell technologies have revealed diverse macrophage subsets and explore the metabolic profile of macrophages in psoriasis. Furthermore, we examine the central role of macrophages in intercellular networks with keratinocytes, T helper 17 (Th17) cells, neutrophils, fibroblasts and sensory neurons.

Additionally, we summarise the novel signal way of macrophages and tissue injury by macrophages. Finally, we summarise emerging therapeutic strategies—including metabolic modulators, signalling pathway inhibitors, advanced delivery systems and cell-based therapies.

By integrating recent insights from single-cell omics, spatial transcriptomics and metabolic studies, this review underscores the potential of macrophage-focused interventions for psoriasis treatment.

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Objective:
This study aims to investigate lifestyle-related factors in patients with psoriatic arthritis (PsA) and their association with disease activity measurements.

Methods:
This multicenter cohort included 938 patients newly diagnosed with PsA, between 2013 and 2023. A composite lifestyle risk score (range 0 to 5) was calculated using five lifestyle-related factors assessed at baseline (BMI outside normal range, abdominal obesity, current smoking, no alcohol consumption, physical inactivity). Higher scores indicate the presence of more lifestyle-related risk factors. One year disease activity outcomes included PsA Disease Activity Score (PASDAS), disease activity in PsA (DAPSA), PASDAS and DAPSA low disease activity (LDA) and remission, and minimal disease activity (MDA).

Results:
The rate of obesity was 33%, abdominal obesity was 51%, current smoking was 19%, and alcohol consumption was 72% with 3% of patients physically inactive. Using multivariable analyses, a higher lifestyle risk score was associated with higher PASDAS (β 0.15; 95%CI 0.08, 0.23), and lower odds for achieving PASDAS-LDA (OR 0.59; 95%CI 0.45, 0.77), and MDA (OR 0.72; 95%CI 0.57, 0.90) at one year follow-up. Similar associations were observed for DAPSA (βadj 1.18; 95%CI 0.65, 1.71) and DAPSA-LDA (OR 0.74; 95%CI 0.59, 0.92). Analysis of individual factors showed that general obesity, abdominal obesity and smoking, were significantly associated with higher PASDAS and DAPSA, and lower odds for achieving PASDAS-LDA and MDA.

Conclusion:
Lifestyle-related risk factors were prevalent in patients with PsA. The associations between lifestyle-related factors and PsA disease activity, mainly obesity and smoking, provide foundation to address lifestyle in PsA care.

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Psoriasis is a chronic inflammatory skin disease influenced by environmental factors, including air pollution. However, large-scale evidence from Asian populations, where particulate matter (PM) exposure is relatively high, remains limited.

This study aimed to evaluate the association between long-term PM exposure and psoriasis incidence, and short-term exposure with exacerbation risk. We conducted a cohort study using the Korean National Health Insurance Service database, involving 8 396 764 individuals.

Long-term exposure was assessed based on annual average concentrations of fine PM (PM2.5) and coarse PM (PM10), while short-term exposure was measured using daily PM levels matched with control days. Long-term exposure to PM2.5 and PM10 was associated with a 19% and 27% higher risk of incident psoriasis (adjusted HR 1.19 and 1.27; 95% CI 1.16–1.22 and 1.25–1.30). Short-term exposure was linked to an increased risk of psoriasis exacerbation (adjusted OR 1.03 for PM2.5, 95% CI 1.00–1.06; adjusted OR 1.01 for PM10, 95% CI 1.00–1.03).

Stronger associations were observed in younger individuals, urban residents, those with lower socioeconomic status, ever-smokers, and patients with comorbid allergic diseases.

These findings suggest that both long-term and short-term PM exposure contribute to psoriasis onset and exacerbation, underscoring air pollution as an important modifiable risk factor in psoriasis development and control.

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Background:
Generalized pustular psoriasis (GPP) is a rare, life-threatening disease attributed to aberrant interleukin-36 (IL-36) activity, often due to variants in the IL-36 receptor antagonist gene. Imsidolimab is a novel, humanized, affinity-matured immunoglobulin G4 monoclonal antibody that binds the IL-36 receptor and antagonizes IL-36 signaling.

Methods:
Two phase 3 trials were conducted at 26 clinical sites within 11 countries investigating imsidolimab treatment for GPP. GEMINI-1 was a double-blind, placebo-controlled trial that randomly assigned 45 patients (18–80 years of age) with a GPP flare to receive either a single intravenous dose of 300 mg of imsidolimab, 750 mg of imsidolimab, or placebo. The primary endpoint was GPP Physician Global Assessment (GPPPGA) scores of clear (0) or almost clear (1) at week 4 (range: 0 [clear] to 4 [severe]; minimally clinically important difference, 1.4). GEMINI-2 was a follow-on relapse prevention trial with a primary objective of evaluating the safety of imsidolimab up to 104 weeks. Patients who improved with treatment in GEMINI-1 were randomly assigned to receive either 200 mg of subcutaneous imsidolimab or placebo monthly, whereas partial responders received open-label 200 mg of subcutaneous imsidolimab monthly.

Results:
In GEMINI-1, 53% of patients in the groups that received either 300 mg (n=8/15) or 750 mg (n=8/15) of imsidolimab had GPPPGA scores of 0 or 1 at week 4, compared to 13% in the placebo group (n=2/15) (P=0.023 for both the 300 mg vs. placebo comparison and 750 mg vs. placebo comparison). In GEMINI-2, no serious adverse events led to imsidolimab discontinuation.

Conclusions:
Compared with placebo, a significantly higher proportion of patients with GPP randomly assigned to receive a single intravenous dose of imsidolimab were clear or almost clear of the disease after 4 weeks based on the GPPPGA. There were no serious adverse events that led to treatment discontinuation with imsidolimab up to 104 weeks of treatment.