SKH-1 mice lack functional hair follicles and display a thickened epidermis closely resembling human skin , this study suggests they could be a valuable tool for probing psoriasis pathogenesis.

Quote:

---

Psoriasis is a complex chronic inflammatory and autoimmune disease; therefore, reliable and human-relevant animal models are essential for preclinical drug testing and mechanistic studies. SKH-1 mice, which lack functional hair follicles and display a thickened epidermis that more closely resembles human skin than that of C57BL/6 mice, represent a potential psoriasis model, but their suitability remains uncertain.

In this study, proliferation, barrier function, differentiation, and inflammatory responses were assessed in the imiquimod (IMQ)-induced dermatitis model of SKH-1 mice using qRT-PCR, immunofluorescence, and flow cytometry. Transcriptomic profiling via RNA sequencing was performed on total RNA from lesional and non-lesional skin of IMQ-induced SKH-1 mice, IMQ-induced C57BL/6 mice, and human psoriatic skin. A psoriasis-like mouse model was also established in SKH-1 mice to evaluate its utility for recurrence studies.

The results showed that the IMQ-induced SKH-1 mouse model exhibited hyperproliferation, hypodifferentiation, barrier disruption, and excessive inflammatory responses similar to human psoriasis. Transcriptomic analysis further highlighted the advantages and complementarity of this model in studying psoriasis pathogenesis, and the established recurrence model provided a suitable tool for investigating the mechanisms of psoriasis recurrence.

This study compared the transcriptomic signatures of lesional skin between IMQ-induced SKH-1 and C57BL/6 mice and demonstrated that the SKH-1 model can recapitulate vascular dysregulation and disease recurrence, indicating that it serves as a valuable complementary tool for probing psoriasis pathogenesis.

Could a B12 delivery system Transcobalamin 2 (TCN2) be a new target for psoriasis ?

Quote:

---

Psoriasis is a chronic immune-mediated inflammatory disorder with systemic implications. While transcobalamin 2 (TCN2) has been linked to several autoimmune diseases, its role in psoriasis remains unclear. Here, we investigated the contribution of TCN2 to psoriatic pathogenesis.

TCN2 expression was significantly elevated in both lesional skin and peripheral blood mononuclear cells (PBMCs) from psoriasis patients, and its levels declined following biologic therapy. Similarly, increased TCN2 expression was observed in imiquimod (IMQ)-induced psoriatic lesions in mice. To further evaluate its function, we generated Tcn2-deficient (Tcn2−/−) mice and established an IMQ-induced psoriasis model. Compared with wild-type controls, Tcn2−/− mice developed attenuated skin lesions with reduced epidermal hyperplasia and inflammation.

Transcriptomic analysis of lesional skin revealed downregulation of inflammatory mediators (S100A7, S100A8, S100A9, IL-1β, IL-6) and suppression of STAT3 signaling in Tcn2−/− mice. In parallel, TCN2-knockdown HaCaT cells exhibited impaired proliferation due to G1-phase arrest, along with reduced expression of proinflammatory factors. Together, these findings demonstrate that TCN2 promotes keratinocyte hyperproliferation and amplifies inflammatory responses in psoriasis.

In conclusion, this study identifies TCN2 as a previously unrecognized regulator of psoriatic inflammation and keratinocyte biology, highlighting its potential as a novel therapeutic target.

European Commission (EC) approves Skyrizi (risankizumab) for the treatment of moderate to severe plaque psoriasis in children and adolescents from the age of 6 years who are candidates for systemic therapy.

Quote:

---

AbbVie today announced that the European Commission (EC) has approved Skrizi (risankizumab) for the treatment of children and adolescents six years of age and older with moderate to severe plaque psoriasis who are candidates for systemic therapy. The approval includes a new 55 mg pre-filled syringe (PFS) to support weight-based dosing for patients weighing less than 40 kg.

"Plaque psoriasis in children carries its own clinical complexity and urgency to provide additional efficacious treatment options," said Roopal Thakkar, M.D., executive vice president, research and development, chief scientific officer, AbbVie. "Today's approval of Skrizi for pediatric psoriasis patients is a meaningful step forward for millions worldwide who are looking for additional treatment options to better manage this chronic disease in their formative years."

Nearly a third of people living with psoriasis develop symptoms before the age of 18, often getting lesions on highly visible areas. Because children often have facial or scalp involvement, the early-onset of psoriasis increases the risk of school absenteeism, potential social stigma, and development of other comorbidities. Despite the significant impact of the disease on children's quality of life, nearly 70% of pediatric patients rely solely on topical therapies.

The EC's approval of Skrizi in pediatric patients is supported by clinical data from the Phase 3 OptIMMize-1 pediatric psoriasis program (NCT04435600), including data from two lead-in pharmacokinetic cohorts: a randomized efficacy assessor-blinded, active-controlled cohort (12 to <18 years), and a single-arm, open-label cohort (6 to <12 years), in addition to the Phase 3 OptIMMize-2 open-label extension study (NCT04862286). The safety profile in pediatric patients (n=137) treated with Skyrizi was consistent with that observed in adults with moderate to severe plaque psoriasis, with no new safety signals observed.

"Particularly for pediatric psoriasis patients, early diagnosis and management can prevent symptoms from worsening and improve quality of life in the long-term," said Nina Magnolo, M.D., Department of Dermatology, University Hospital of Münster, and lead investigator of the OptIMMize-1 study. "The EC's approval of risankizumab provides younger patients with more options including weight-based dosing and allows physicians to address unmet clinical needs of children living with moderate to severe psoriasis with confidence."

This study analysed the U.S. Food and Drug Administration’s Adverse Event Reporting System (FAERS) adverse event reports to evaluate the safety profiles of Bimzelx (bimekizuma).

Quote:

---

Objective:
To evaluate adverse events (AEs) associated with Bimekizumab through data mining of the U.S. Food and Drug Administration’s Adverse Event Reporting System (FAERS), aiming to explore potential drug-related AEs and provide guidance for clinical medication safety.

Methods:
AE reports related to Bimekizumab from the fourth quarter of 2023 to the fourth quarter of 2024 were extracted from the FAERS database. The reports were classified and grouped according to risk signals based on Preferred Terms (PT) and System Organ Classes (SOC).

Results:
Among 7444 AE reports where Bimekizumab was identified as the primary suspected drug, 78 PTs of AEs were identified, spanning 23 different SOCs. Females accounted for a higher proportion of AE reports than males (54.35% vs. 37.86%), with the 45- to 59-year age group reporting the most cases (11.32%). The median time to AE onset was 32.00 days (interquartile range: 0.00–100.00 days), with the majority occurring more than 60 days after administration (n = 189, 10.09%). Among the significant positive risk signals, PTs such as Candida infection, streptococcal and staphylococcal infections, tonsillitis, otitis media, kidney and skin infections, oral herpes, acne, injection-site pain, positive Mycobacterium tuberculosis complex test, latent tuberculosis, inflammatory bowel disease, and suicidal depression demonstrated high signal intensity and substantial reporting frequency, aligning closely with the drug’s prescribing information. Additionally, the study identified several AEs not explicitly mentioned in the label, including Mycoplasma pneumonia, Lyme disease, cellulitis, erysipelas, lung abscess, pertussis, rectal abscess, staphylococcal sepsis, subcutaneous abscess, eye infection, diabetic foot, skin plaques, disorder and discoloration, injection-site induration, warmth and pruritus, angular cheilitis, coated tongue, chapped lips, hemorrhagic diarrhea, pharyngeal ulceration, genital pruritus, and blepharitis.

Conclusion:
Bimekizumab carries the risk of inducing multiple AEs during treatment. In clinical practice, close monitoring of infections and infestations, general disorders and administration-site conditions, gastrointestinal disorders, skin and subcutaneous tissue disorders, and psychiatric disorders is advised. Should any AEs or disease progression occur, timely intervention measures must be implemented to prevent severe systemic damage and clinical deterioration.

This multicentre case control study included 3069 patients with psoriasis and 7041 healthy controls suggests dsDNA could be a trigger of and biomarker for psoriasis and warrants further exploration.

Quote:

---

Psoriasis is a recurrent autoimmune disease. No biological factor that is associated with the risk of psoriasis has been definitively identified. The potential role of the immunogen double-stranded (ds)DNA as a trigger of and biomarker for psoriasis warrants exploration.

This multicentre case–control study included 3 069 patients with psoriasis and 7 041 healthy controls from 12 regions in China. The associations of the serum dsDNA level with the psoriasis risk and severity were analysed in the overall population. The serum dsDNA level was significantly higher in patients than in controls. Each 0.1 ng/mL increase in serum dsDNA was significantly associated with increased odds of psoriasis (adjusted odds ratio, 1.45; 95% confidence interval, 1.40–1.48; p < 0.001).

The optimal serum dsDNA cutoff value for the diagnosis of psoriasis was 1.11 ng/mL, with 61.6% sensitivity and 74.8% specificity. A significant dose–response relationship was observed between the serum dsDNA level and the risk of psoriasis-associated morbidity when using the optimal dsDNA cutoff value as the reference. Serum dsDNA levels were positively associated with higher PASI and BSA scores and the severity of psoriasis.

These findings suggest that serum dsDNA level is strongly associated with psoriasis morbidity and severity.

Zasocitinib significantly outperforms Sotyktu (Deucravacitinib) in head to head phase 3 psoriasis study, promising to redefine oral treatment expectations.

Quote:

---

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.

This study introduces multiphoton tomography equipped with fluorescence lifetime imaging (MPT-FLIM) as an intravital diagnostic tool to assess the morphological and metabolic course of psoriasis and track drug delivery during topical treatment with calcipotriol and betamethasone dipropionate (C/B) or calcipotriol derivative (C/-)

Quote:

---

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.

These findings provide reassurance to clinicians and patients and support current recommendations endorsing uninterrupted biologic treatment and routine vaccination for individuals with psoriasis.

Quote:

---

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.

This study demonstrates that methyltransferase-like 1 (METTL1), an m7G methyltransferase, is significantly upregulated in epidermal keratinocytes of human psoriatic lesions.

Quote:

---

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.

A list of medications I have tried…


Pills

Soriatane
Methotrexate
Cyclosporine
Otezla
Sotyktu
Icotrokinra

Biologics

Humira
Cimzia
Enbrel
Stelara
Trymfa
Skyrizi
Ilumya
Cosentyx
Taltz
Silq
Bimzelx

The medications left…

Cyclosporine - I would rather die.
Sotoktu - Low on the priority list.
Icotrokinra - It’s an IL23. No thanks
Ilumya - It’s an IL23. No thanks
Silq - It’s not approved for arthritis. No thanks.
Bimzelx - High on the priority list.

This trial to evaluate Bimzelx (bimekizumab) in Chinese patients with psoriasis, represents the largest clinical trial of bimekizumab conducted in an Asian population to date.

Quote:

---

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.

Uncovering why inflammatory bowel disease patients face higher psoriasis risks and the role of epidermal growth factor receptor, body mass index and air quality.

Quote:

---

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.

Icotyde (icotrokinra) demonstrated high rates of overall skin, scalp, genital and hand/foot psoriasis clearance, and improvements in nail psoriasis, through 1 year.

Quote:

---

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.

Initial study reports distinct improvement from "Ozone Sauna & Ozonated Olive Oil" in the treatment of psoriasis with minimal risk.

Quote:

---

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.

This review suggests macrophages might be the key to unlocking better psoriasis treatments.

"Macrophages are a type of white blood cell of the innate immune system that engulf and digest pathogens, such as cancer cells, microbes, cellular debris and foreign substances, which do not have proteins that are specific to healthy body cells on their surface"

Quote:

---

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.

My PsA has added Plantar Fasciitis to it's never ending array of gifts. It's really a bit of body wack-a-mole. Fix one thing, and another will crop up. Anyway my Dr recommends Crocs, but they're very expensive here, and not really practical for our wet winters. Anyone have any experience with this and perhaps have other recommendations?

Does your lifestyle affect your psoriatic arthritis (PsA) ? this study looked at the latest research.

Quote:

---

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.

A Korean nationwide cohort study looking at particulate matter (PM) and onset and exacerbation of psoriasis.

Quote:

---

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.

Vanda Pharmaceuticals publish efficacy and safety results of Imsidolimab for generalised pustular psoriasis (GPP)

Quote:

---

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.