Balinatunfib is being developed as a potential new treatment for patients with psoriasis and other inflammatory diseases, it is the first oral medicine that selectively inhibits TNFR1 signalling to potentially stop or slow the disease-causing processes, while preserving signals initiated through TNFR2.

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Background:
Activation of tumour necrosis factor receptor 1 (TNFR1) promotes inflammation in several autoimmune diseases.

Objectives:
To evaluate safety, tolerability and clinical efficacy of balinatunfib versus placebo in patients with mild-to-moderate psoriasis.

Methods:
Phase-1, 4-week, randomized, double-blind, placebo-controlled pilot study, including patients aged 18–65 years with chronic plaque-type psoriasis with mild-to-moderate severity as defined by Psoriasis Area Severity Index (PASI ≤16) and ≥2 lesions with a Target Lesion Severity Score (TLSS) ≥4 at both screening and baseline. The primary endpoint was safety and tolerability of balinatunfib as assessed by the incidence of adverse events (AEs), treatment-emergent AEs (TEAEs) and AEs of special interest. Secondary endpoints were the percent change in TLSS from baseline to Weeks 2 and 4. Serum biomarkers, interleukin-22 (IL-22), IL-17F and percent change in PASI from baseline to Weeks 2 and 4, were also evaluated.

Results:
38 male patients (age [mean ± SD], 43 ± 10.6) were randomized to receive 200-mg balinatunfib (N = 26) or placebo (N = 12). No serious or severe TEAEs or adverse events of special interest were observed during the study. Dysgeusia (61.5% vs. 0%) and nausea (19.2% vs. 0%) were the most frequently reported TEAEs in the balinatunfib versus the placebo groups. Balinatunfib showed improvements from baseline in TLSS vs. placebo at Week 2 (17.06% vs. 6.29%, p = 0.032) and Week 4 (38.18% vs. 20.44%, p = 0.012). Exploratory analyses suggested an improvement in the total PASI scores at Week 2 (17.73% vs. 4.12%, nominal p = 0.005), Week 4 (35.09% vs. 15.71%, nominal p = 0.009) and decreased serum levels of IL-22 (nominal p = 0.0001) and IL-17F (nominal p = 0.0025) with balinatunfib treatment.

Conclusion:
Patients with mild-to-moderate psoriasis treated with balinatunfib reported no severe or serious TEAEs and showed promising clinical responses, suggesting that further evaluation of TNFR1 signal inhibition in inflammatory diseases is warranted.

These results suggest that the LIGHT/TNFSF14 axis may play a key role in regulating cytokine production by autoimmune cells and related pathways in psoriasis.

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Background:
The pathogenesis of psoriasis is associated with abnormalities in immune pathways. HVEM is known as a receptor of LIGHT (homologous to lymphotoxins, inducible, and competes with HSV glycoprotein D), which is a newly identified member of the TNF superfamily. The expression of HVEM and LTBR (another LIGHT receptor) has been found to be increased in the skin of psoriasis patients. This indicates the potential role of LIGHT and its receptors in the pathogenesis of psoriasis. Therefore, the objective of this study was to examine the effect of LIGHT on keratinocyte proliferation and its therapeutic potential in the treatment of psoriasis.

Methods:
We used immunohistochemistry to examine their expression in psoriasis-affected and normal tissue samples. We treated cells of the keratinocyte cell line HaCat with LIGHT protein, anti-HVEM and anti-LTβR antibodies, HVEM interference and LTβR interference RNA vectors, and NF-κB and JNK/AP-1 inhibitors at various concentrations and for various times, separately or simultaneously. The expression of NF-κB was examined by immunofluorescence staining, and the expression of inflammatory proteins was measured with ELISA. Further, the viability of HaCat cells was examined with a CCK-8 kit. In addition, flow cytometry was used to detect the expression of HVEM and LTBR on HaCat cells.

Results:
We found that LIGHT treatment of HaCat cells promoted the nuclear translocation of NF-κB. Further, the expression of p-c-Jun, IL-6, IL-8, PGI2, and PTGS2 was increased in response to LIGHT treatment, but the expression of these factors was decreased when the LIGHT receptors were blocked or NF-κB and JNK/AP-1 expression was inhibited. We also found that the viability of HaCat cells was consistent with the expression of pro-inflammatory factors.

Conclusions:
The present findings indicate that the JNK/AP-1-HVEM-LIGHT pathway played a role in the viability of human keratinocytes and the expression of IL-6, IL-8, PGI2, and PTGS2. Thus, the JNK/AP-1-HVEM-LIGHT pathway might be a potential target for the treatment of psoriasis.

This study identifies a novel role for G protein-coupled receptor 108 (GPR108) as a negative regulator of TLR7 signalling in psoriasis and may yield new therapeutic principles for managing psoriatic diseases.

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Objective:
Psoriasis, a common chronic inflammatory skin disease, is characterized by epidermal hyperplasia and inflammatory cell infiltration. While endosomal Toll-like receptors (TLRs), particularly TLR7, are key drivers of psoriatic exacerbations, the regulatory mechanisms governing TLR7 activity in psoriasis remain incompletely understood. This study aims to investigate the role of G protein-coupled receptor 108 (GPR108) in regulating TLR7 activity during imiquimod (IMQ)-induced psoriasiform dermatitis.

Methods:
We established IMQ-induced psoriasiform lesions in Gpr108-null mice, as well as IMQ-treated GPR108-deficient keratinocyte and macrophage models. The psoriasis-like phenotype was assessed in vivo using PASI scoring and H&E staining. Protein expression was examined by Western blotting, immunohistochemistry, and immunofluorescence. Additionally, RNA-seq and flow cytometric analyses were performed to verify the involvement of the TLR7/NF-κB signaling in regulating GPR108-deficient macrophage polarization.

Results:
We found that Gpr108 deficiency exacerbates IMQ-induced psoriatic lesions in mice. Mechanistically, GPR108 deficiency enhances TLR7/MyD88/NF-κB signaling in both keratinocytes and macrophages following imiquimod stimulation. This increased TLR7 activation promotes keratinocyte hyperproliferation and dysregulated differentiation, and alters the M1/M2 macrophage balance, leading to elevated production of cytokines, including TNF-α and IL-6.

Conclusion:
GPR108 functions as a negative regulator of TLR7 signaling in psoriasis.

This review aims to examine the alterations in neural innervation within psoriatic skin and delineate the functional contributions of sensory neuron-derived mediators—including ion channels, receptors, and neuropeptides—in modulating psoriasis-associated immune dysregulation.

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Psoriasis is a chronic inflammatory skin disease characterized by abnormal proliferation of epidermal cells induced by an overactive immune system. In addition to the interaction between immune cells and keratinocytes, emerging research highlights the indispensable role of peripheral sensory neurons in the initiation and progression of psoriatic inflammation.

Sensory neurons not only perceive various external stimuli but also participate in skin immune regulation and barrier repair through the release of neuropeptides and neurotransmitters.

This review systematically compiles current research advancements concerning the altered neural innervation patterns in psoriatic lesions, the pathophysiological functions of sensory neuron-specific receptors and ion channels, and the regulatory mechanisms of neuropeptides in disease pathogenesis.

By elucidating the precise contributions of sensory neurons to the development of psoriasis, this work seeks to further clarify their specific role in the disease and provide new insights for enhancing the understanding of its pathogenesis, thereby informing the development of more targeted therapeutic strategies.

In this cross-sectional analysis of a large, real-world Canadian cohort, G2-PASE demonstrated very strong correlation and excellent reliability compared with PASI.

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Background:
The Psoriasis Area and Severity Index (PASI), a composite measure of plaque psoriasis disease severity, is commonly used to determine treatment eligibility and response, but is time consuming for every-day clinical use. The Gulliver-Gestalt-Psoriasis Area Severity Estimate (G2-PASE) was developed to approximate PASI scores using Physician Global Assessment (PGA) and body surface area (BSA) measures.

Objectives:
To determine the reliability and validity of G2-PASE compared to PASI using data from a multi-center, Canadian cohort of patients with plaque psoriasis.

Methods:
Canadian patients with a history of moderate to severe plaque psoriasis enrolled in the first cohort of the Psoriasis Longitudinal Assessment and Registry (PSOLAR 1; a global, prospective, longitudinal, disease-based registry) were included. The G2-PASE for each patient was calculated by applying baseline PGA and BSA values available from PSOLAR patient data at enrollment. The correlation and reliability of G2-PASE compared to PASI for each patient at enrollment was then assessed. A similar analysis was conducted to test the reproducibility of results previously published by a participating PSOLAR clinical trial site.

Results:
Of the 1896 Canadian patients in PSOLAR 1, 1803 had PASI data and were included in this analysis. The average baseline PASI score was 5.52 (SD 6.44, range 0.00–64.30), and the mean calculated G2-PASE score was 8.37 (SD 7.51, range 0.00–45.00). The Pearson's correlation coefficient was 0.83 (p < 0.0001), indicating very strong and significant correlation between PASI and G2-PASE scores. The standardized Cronbach coefficient alpha was 0.91. Results from the Canadian PSOLAR cohort are similar to those of patients enrolled at the New Lab Clinical Research Inc. site and complement findings previously reported from this site.

Conclusions:
This study validates G2-PASE as a reliable measure of plaque psoriasis severity when compared to PASI among a large cohort of patients with predominantly moderate to severe disease.

A team of researchers from the Department of Medicine 3 – Rheumatology and Immunology at Uniklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), have now discovered which cells migrate from the skin of psoriasis patients to the joints and how they trigger inflammation there.

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Firstly: How inflammatory cells travel from the skin to the joints:
Psoriasis triggers the production of special precursor cells from the immune system in the inflamed skin. “These cells can migrate from the skin to the bloodstream and from there to the joints,” explains Dr. Simon Rauber, head of the working group at Department of Medicine 3. “It is interesting that the mere migration of immune cells into the joint is not sufficient to trigger inflammation there.”

Secondly: How inflammatory cells infiltrate the joint:
It is crucial to examine the processes that take place in the joint. Here, the migratory immune cells encounter connective tissue cells known as fibroblasts that are usually less than pleased to encounter these new arrivals. “The protective function of these connective tissue cells is usually considerably reduced in people who develop psoriatic arthritis,” says Prof. Dr. Andreas Ramming, team leader and deputy head of department at Department of Medicine 3. “As a result, the inflammatory cells that enter the joint cannot be brought into check, and go on to trigger an inflammatory reaction in the joint.” The results provide an explanation for why some psoriasis patients go on to develop joint disease as well.

Early detection and prevention before the disease affects the joints:
As the migratory immune cells can already be detected in the blood before triggering inflammation in the joints, this could act as an early warning signal in future, allowing patients at risk to be identified in time. In future, treatment strategies could be aimed specifically at intercepting these inflammatory cells and preventing them from triggering inflammation in the joints.

Apologies if this has been covered before but I wasn't able to find anything recent.

Following recent knee pain my Rheumy refereed me to an Orthopedic Surgeon. X-rays etc later it shows my left knee joint is totally messed up. I had a previous surgery on it in 2007 but now the PsA has done a number on the ACL tendon where it joins the bone, which is almost completely pulled loose and is ripping my meniscus. So I have a total knee replacement scheduled for a couple of weeks from now.

Does anyone have a real world experience that they can share? Especially on how the recovery period went.

This study explored the global prevalence of obesity, abdominal obesity, and being overweight in patients with psoriatic arthritis (PsA).

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Background:
Although the risk of psoriatic arthritis (PsA) and obesity comorbidities is increasing, only a few systematic global prevalence studies have been conducted.

Objective:
This study explored the global prevalence of obesity, abdominal obesity, and being overweight in patients with PsA.

Methods:
We examined eight databases from their inception to November 20, 2024. The R language was used for the data analysis. Meta-regression and subgroup analyses were used to evaluate the heterogeneity of the pooled studies. Funnel plots and Egger's tests were used to assess publication bias in the included studies, and the trim-and-fill method was used to correct for bias.

Results:
Twenty-seven studies were included. The overall prevalence of obesity in patients with PsA was 35% (95% CI, 0.30 to 0.40). The prevalence of obesity in adults with PsA was 35% (95% CI, 0.28 to 0.42), and it was 27% (95% CI, 0.11 to 0.46) in children and adolescents. Africa had the highest prevalence (57%; 95% CI, 0.43 to 0.69). In contrast, the prevalence was the lowest in Europe at 31% (95% CI, 0.25 to 0.38). In terms of countries, China had the highest prevalence (65%), followed by Egypt (57%) and Norway (55%). The lowest prevalence was observed in the United States (20%).

Conclusions:
These findings confirm the association between obesity and PsA. Considering the negative impact of obesity on PsA treatment, the early detection and management of obesity should be prioritized. Further population-based prospective observational studies are required to clarify the mechanisms underlying the coexistence of obesity in patients with PsA.

Curcumin solid lipid nanoparticles (CUR-SLN) represents a promising and safer topical therapeutic strategy for psoriasis.

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Psoriasis is a chronic inflammatory skin disorder in which existing topical and systemic therapies are often limited by adverse effects and poor patient compliance. This study aimed to develop a curcumin-loaded solid lipid nanoparticle CUR-SLN (curcumin solid lipid nanoparticles) loaded nanogel to enhance topical delivery and therapeutic efficacy.

CUR-SLNs were prepared using a solvent diffusion method and characterized for particle size, polydispersity index (PDI), zeta potential, entrapment efficiency, and morphology. The optimized nanoparticles (133.90 ± 2.45 nm; PDI 0.325 ± 0.21; entrapment efficiency 89.50% ± 4.52%) were incorporated into a Carbopol-based gel to formulate the CUR-SLN nanogel.

The nanogel was evaluated for appearance, viscosity, pH, and texture profile, along with in vitro drug release, ex vivo skin permeation, drug retention, and stability. Compared with a conventional curcumin gel, the CUR-SLN-loaded nanogel demonstrated sustained drug release over 48 h and significantly enhanced skin permeation and retention. In vivo studies in a psoriasis-induced mouse model showed a marked reduction in Psoriasis Area and Severity Index scores and significant downregulation of key pro-inflammatory cytokines (interferon-α [IFN-α], IL-23, interleukin-17 [IL-17], tumor necrosis factor-α [TNF-α]) (p < 0.001).

Histological evaluation further confirmed restoration of normal skin structure in treated animals. Overall, the CUR-SLN-loaded nanogel represents a promising and safer topical therapeutic strategy for psoriasis, supporting its potential for further clinical development.

This study was an observational, prospective, multicentre, real-world study in moderate-to severe plaque psoriasis patients treated with Siliq / Kyntheum (brodalumab) in Greece.

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Background:
Prospective, multicenter, real-world studies on brodalumab's effectiveness and safety in patients with moderate-to-severe psoriasis are lacking.

Objectives:
The RESOLVE study was an observational, prospective, multicenter, real-world study in moderate-to severe plaque psoriasis patients treated with brodalumab in Greece. The primary objective was to assess the proportion of patients achieving absolute Psoriasis Area and Severity Index (PASI) ≤ 3 after 12 weeks (W12) of treatment and, in those who continued brodalumab after W12, the percentage achieving static Physician's Global Assessment (sPGA) success (“clear/almost clear”) after 52 weeks (W52). Secondary objectives included patients' profile, Patient Reported Outcomes and adverse events' frequency/severity.

Methods:
Analyses were conducted using the as-observed data. Two imputation methods were applied for the missing data: “last observation carried forward” and “worst-case” scenario. Continuous variables were reported using summary statistics, whereas for categorical variables frequency tables were used.

Results:
One hundred and forty-five patients who initiated treatment with or switched to brodalumab were enrolled. Based on the “as-observed data,” 76.4% of patients achieved absolute PASI ≤ 3 at W12, 97.9% continued brodalumab after W12% and 96.1% achieved sPGA success [“clear” or “almost clear” skin (i.e. 0 or 1)] at W52. At W12 i) 78.5%, 68.1% and 53.5% achieved PASI75/90/100, respectively and ii) 71.5% and 54.2% of patients achieved sPGA0/1 and sPGA 0, respectively. The median time [(95% confidence interval (CI)] to achieve PASI ≤ 3 was 13.1 (13.0, 13.6) weeks. From baseline to W12 and W52 (i) mean DLQI scores decreased by 9.3 ± 6.0 and 12.6 ± 6.2, (ii) 52.6% and 81.9% of patients reported being “free of symptoms” and (iii) 57.4% and 82.7% of patients, responded being “extremely satisfied with treatment,” respectively.

Conclusions:
Brodalumab treatment demonstrated clinically relevant short- and long-term effectiveness in real-world patients with moderate-to-severe psoriasis and improvement in quality of life.

This study assessed Humira (adalimumab) efficacy and drug survival in routine Australian clinical practice on patients with psoriasis.

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Background:
Although adalimumab has shown strong efficacy and safety in clinical trials, real-world evidence in Australian patients with moderate-to-severe chronic plaque psoriasis is limited. This study assessed adalimumab efficacy and drug survival in routine clinical practice, comparing outcomes with the Phase 3 REVEAL trial and its open-label extension.

Methods:
Data were extracted from the Australasian Psoriasis Registry for adults meeting Pharmaceutical Benefits Scheme criteria to be prescribed adalimumab for chronic plaque psoriasis. Baseline demographics, Psoriasis Area and Severity Index (PASI) scores and treatment history between June 2006 and March 2022 were analysed. Drug survival was evaluated using Kaplan–Meier and Cox regression.

Results:
A total of 306 patients were included; 59.8% had prior biologic exposure compared to 12.8% in REVEAL. The mean baseline PASI was 24.1 and at 3 months, 63.5% achieved PASI75 while 33.6% achieved PASI90. PASI90 responses remained stable through 3 years and exceeded REVEAL extension rates beyond 18 months. Median drug survival was 27.9 months; survival was 97.7%, 78.6%, 63.7% and 51.0% at 3, 9, 15 and 27 months, respectively. Male sex and achieving PASI ≤ 2 predicted longer drug survival.

Conclusions:
In Australian real-world practice, adalimumab demonstrated sustained effectiveness and drug survival in patients with chronic plaque psoriasis comparable to RCTs, despite higher baseline disease severity and greater prior biologic exposure.

I'm aware that being quick to anger is a symptom of the inflammation this damn disease causes. Does anyone have suggestions for anything that actually works to keep it under control? I experience it and then am immediately overwhelmed with remorse, to the extent of getting emotions that are difficult to cope with at times. I find myself disassociating more and more for fear of it happening, which is probably the exact opposite of what I need. 

Any suggestions or experience will be helpful.

This study evaluated the diagnostic accuracy of multiphoton microscopy (MPM) in psoriasis and its potential application in therapeutic monitoring.

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Background and Objectives:
Psoriasis is a chronic inflammatory skin disease, and noninvasive diagnostic tools are essential for accurate diagnosis and treatment monitoring. Multiphoton microscopy (MPM) enables real-time, noninvasive skin imaging with submicron resolution. This study evaluated the diagnostic accuracy of MPM in psoriasis and its potential application in therapeutic monitoring.

Patients and Methods:
This prospective observational study enrolled 34 patients with psoriasis. It comprised three parts: (1) analysis of imaging features of lesional and nonlesional skin using multiphoton microscopy (MPM; Transcend Vivoscope); (2) evaluation of the diagnostic performance of MPM parameters compared with reflectance confocal microscopy (RCM); and (3) prospective monitoring of 24 patients treated with Benvitimod (Tapinarof) cream for 8 weeks (T0/T1/T2).

Results:
MPM detected psoriasis characteristics (including hyperkeratosis, parakeratosis, an absent stratum granulosum, enlarged nucleus diameter, and absent bright rimming) with comparable diagnostic efficiency to RCM (AUC = 0.838, p < 0.001 vs. 0.824, p < 0.001). Psoriatic lesions showed significant perinuclear fluorescence accumulation compared to healthy skin (p < 0.001). All imaging features improved significantly after 8 weeks of treatment (p < 0.001). PASI/TLS scores showed correlations with the epidermal thickness (r = 0.403/0.492, p < 0.001), nuclear diameter (r = 0.4/0.375, p < 0.001), and fluorescence intensity (r = –0.419/–0.492, p < 0.001).

Conclusions:
MPM is a novel and non-invasive imaging technique for psoriasis evaluation and treatment monitoring.

If you are using injections for psoriasis which type do you prefer, pen type (auto injector) or prefilled syringe ?

Members and guests can vote in the poll above, and our members are welcome to post in this thread too if they wish.

Efficacy and safety of Rinvoq (upadacitinib) in palmoplantar pustulosis study highlights the complex immune response patterns.

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Background and objectives: 
Palmoplantar pustulosis (PPP) is a chronic and refractory inflammatory skin disorder with unclear pathogenesis.

Patients and methods: 
Ten PPP patients treated with upadacitinib were monitored to assess efficacy and safety. Immunofluorescence and immunohistochemistry were employed to evaluate Th1, Th2, and Th17 cell expressions, along with their associated cytokines in lesions on palms or soles from 16 PPP patients, 10 chronic eczema (CE) patients, 10 psoriasis vulgaris (PV) patients, and 7 healthy controls (HC).

Results:
 In PPP patients receiving upadacitinib, the shortest time to achieve PPPASI75 and PPPASI90 was 4 weeks and 8 weeks, respectively. The rates of patients achieving PPPASI90 at week 16, week 24, and week 52 was 70 %, 100 %, and100 %, respectively. Th1 cells and IFN-γ levels in PPP were comparable to CE and PV, and higher than HC. Th2 cells, IL-4, and IL-13 levels in PPP were similar to CE, and greater than HC and PV. Th17 cells, IL-17, and IL-36γ levels in PPP were comparable to PV, and more abundant than HC and CE.

Conclusions: 
Upadacitinib is a safe and effective option for PPP patients, which may be attributed to the complex Th1, Th2, and Th17 inflammatory responses associated with PPP.

This study suggests TYK2 inhibitors for psoriasis show improvements in both skin and mood symptoms and enhanced patient adherence to treatment regimens.

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Background:
Psoriasis and depression frequently coexist, creating a complex, bidirectional relationship that complicates treatment. This study, integrating clinical assessments with transcriptomic and metabolomic analyses, hypothesizes that TYK2 (tyrosine kinase 2) inhibitors possess a dual therapeutic potential to simultaneously address both dermatological manifestations of psoriasis and the frequently accompanied depressive symptoms.

Methods:
In a cohort of 298 psoriasis patients evaluated using the Hospital Anxiety and Depression Scale (HADS), participants were categorized into a TYK2 inhibitor group, a Janus kinase (JAK) inhibitor group, and a non-JAK pool (comprising interleukin [IL]-23 biologics, IL-17 biologics, and other treatments) to avoid overlapping JAK pathway inhibition. Statistical analysis was conducted using generalized linear models (GENMOD), with adjustments for the following covariates: age, sex, Psoriasis Area and Severity Index (PASI), body surface area (BSA), prior systemic or biologic therapy within 12 months, disease duration, and phototherapy history.

Results:
For HADS-D scores, the TYK2 inhibitor group showed significantly lower values compared with the non-JAK pool (β = 1.23, 95% confidence interval [CI]: 0.37–2.10). However, no significant differences were observed when compared with the IL-23 biologics group (β = 0.67, 95% CI: −0.76–2.10) or the JAK inhibitor group (β = 0.84, 95% CI: −1.54–3.21). Transcriptomic analysis of peripheral blood revealed significant downregulation of genes related to the IL-6 receptor, long-term depression pathways, and Th17 cell differentiation, while pathways associated with neuronal activity were upregulated. Metabolomic profiling highlighted a decrease in kynurenic acid, which is known for its pro-inflammatory and depressive effects, and an increase in 1H-indole-3-propanoic acid, an anti-inflammatory metabolite with neuroprotective properties. It is important to note that these findings are based on exploratory omics analyses, for which false discovery rate (FDR) control was applied.

Conclusions:
These findings provide a hypothesis that TYK2 inhibitors disrupt the persistent “peripheral inflammation–central depression” cycle by targeting the IL-23/Th17 axis and modulating the IL-6/tryptophan metabolic hub. This innovative, multi-targeted approach represents a possibility for treating psoriasis with comorbid depression, offering not only clinical improvements in both skin and mood symptoms but also enhanced patient adherence to treatment regimens.

Could cobalt phosphide nanoparticles deposited on carbon polyhedral framework help psoriasis ? This study suggests it could.

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Psoriasis, a chronic inflammatory skin disease characterized by oxidative stress and dysregulated immunity, necessitates innovative therapies to overcome the limitations of conventional treatments. This study introduces cobalt phosphide nanoparticles deposited on carbon polyhedral frameworks (CoP-C PFs) as a multifunctional nanoplatform integrating enzyme-mimicking catalysis and photothermal activity for synergistic psoriasis management.

CoP-C PFs exhibit superior catalytic efficiency, with low Michaelis-Menten constants (e.g., Km = 0.26 mM for H2O2 decomposition), enabling potent reactive oxygen species (ROS) scavenging to alleviate oxidative damage in RAW264.7 macrophages and HaCaT keratinocytes. Under 808 nm near-infrared irradiation, CoP-C PFs exhibit a high photothermal conversion efficiency of 68.6%, enabling precise control of the local temperature to generate localized hyperthermia to enhance catalytic ROS elimination and antibacterial activity.

In an imiquimod-induced psoriatic murine model, CoP-C PFs alleviated inflammation by restoring redox balance, suppressing CD3+ T cell/F4/80+ macrophage infiltration, modulating IL-17A/IL-23 and TNF-α/NF-κB pathways, and promoting M2 macrophage polarization (increased CD206+/CD68+ ratio), resulting in epidermal normalization and reduced abnormal keratinization without organ toxicity, underscoring effectiveness and biosafety.

By integrating photothermal enhancement with multienzyme catalysis, this “all-in-one” nanozyme platform enables dual regulation of oxidative stress and immune microenvironment, offering a promising therapeutic strategy for psoriasis and other inflammatory skin disorders.

This study aimed to evaluate the expression of Enhancer of Zeste Homologue 2 (EZH2) across immune cell subsets in the peripheral blood of patients with psoriasis.

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Enhancer of Zeste Homologue 2 (EZH2) is an epigenetic regulator involved in immune cell differentiation and function; however, its role in psoriasis remains unknown.

This study aimed to evaluate EZH2 expression in peripheral blood mononuclear cells from patients with psoriasis and explore its potential functional relevance to disease pathogenesis. Peripheral blood samples were obtained from 40 psoriasis patients and 18 healthy controls, and EZH2 expression in T cell and monocyte subsets was analysed by flow cytometry. EZH2 expression was significantly reduced in circulating CD8+ naïve and memory T cells, as well as in monocyte subsets from psoriasis patients compared to healthy controls. EZH2 levels in CD8+ naïve T cells showed a significant inverse correlation with disease severity scores.

Functional analyses revealed that pharmacological EZH2 inhibition suppressed IL-17A expression in peripheral blood mononuclear cells under IL-23/IL-1β stimulation. In addition, immunofluorescence staining identified EZH2-positive T cells and monocytes within psoriatic skin lesions.

Collectively, these findings suggest that EZH2 may be involved in the regulation of type 3 inflammatory responses and may therefore represent an epigenetic regulator contributing to psoriasis pathogenesis.

This was passed to me by Waine

Taltz (ixekizumab) and Zepbound (tirzepatide) used together delivered superior efficacy in first-of-its-kind Phase 3b trial for adults with active psoriatic arthritis and obesity or overweight.

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Eli Lilly and Company announced positive topline results from the novel TOGETHER-PsA open-label Phase 3b trial evaluating the concomitant use of Taltz (ixekizumab) and Zepbound (tirzepatide) compared to Taltz alone in adults with active psoriatic arthritis (PsA) and obesity or overweight with at least one weight-related condition. At 36 weeks, treatment with concomitant Taltz and Zepbound met the primary and all key secondary endpoints for superiority to Taltz monotherapy. TOGETHER-PsA is the first controlled study to evaluate an incretin therapy used with a PsA biologic. An estimated 65% of adults with PsA in the U.S. also have obesity (BMI ≥30 kg/m²) or overweight (BMI 27-29.9 kg/m²) with at least one additional weight-related comorbidity, highlighting a need for integrated treatment approaches that address the full burden of their diseases.

In the study, 31.7% of patients in the Taltz plus Zepbound treatment arm achieved a 50% improvement in PsA activity, based on American College of Rheumatology 50 (ACR50), and weight reduction of at least 10%, compared to 0.8% of patients on Taltz monotherapy, meeting the primary endpoint (p<.001). In a key secondary endpoint, Taltz plus Zepbound delivered a 64% relative increase over Taltz monotherapy in the proportion of patients who achieved ACR50 (33.5% of patients vs. 20.4%, respectively, p<.05), demonstrating that treatment of obesity or overweight with Zepbound reduced the burden of PsA. The study population included patients with a high disease burden at baseline and an average BMI of 37.6 kg/m2 across both arms. Patients had high disease activity and meaningful functional impairment. More than 60% had prior experience with one or more advanced therapies, reflecting a difficult-to-treat patient population.

"TOGETHER-PsA represents a pioneering first step leveraging Lilly's leadership in incretin science to deliver a major advance in disease outcomes for people living with the cumulative burden of psoriatic arthritis and obesity or overweight," said Mark Genovese, M.D., senior vice president of Lilly Immunology development. "This is the first controlled pharmacologic study to demonstrate that treatment of obesity improved PsA disease measures, and we are particularly impressed with the findings showing significant improvement in PsA disease activity with Zepbound used alongside Taltz, an already rapid-acting and durable PsA treatment. These results demonstrate how an integrated treatment approach has the potential to improve the standard of care in a compelling and comprehensive way."

Adverse events in participants treated with concomitant administration of Taltz and Zepbound were generally mild to moderate, and the types of adverse events were consistent with the known safety profile of each medicine. The most common adverse events occurring in ≥5% of participants were nausea, diarrhea, constipation and injection site reactions in the concomitant treatment arm, and injection site reactions and upper respiratory tract infections in the Taltz monotherapy arm.

Taltz is a monoclonal antibody that selectively binds with interleukin 17A (IL-17A) cytokine and inhibits its interaction with the IL-17 receptor. Zepbound is the only FDA-approved dual GIP (glucose-dependent insulinotropic polypeptide) and GLP-1 (glucagon-like peptide-1) receptor agonist obesity management medication.

"While treatment guidelines for psoriatic arthritis recommend management of obesity, the reality is these two chronic diseases are often addressed separately and moving the needle in psoriatic arthritis has remained challenging," said Joseph F. Merola, M.D., Professor and Chair, Department of Dermatology and Professor of Internal Medicine in the Division of Rheumatic Diseases, UT Southwestern Medical Center. "The observed benefit with treatment using Taltz and Zepbound appears to meaningfully impact psoriatic disease activity, indicating that for many patients, PsA is an obesity-related condition. This integrated therapy approach represents a potential paradigm shift and could lead to better outcomes for those living with both diseases."

Hi,

I'm from Cape Town, South Africa and am in my mid 50s. Have been diagnosed with PsA since 2020 but have had it probably since 2007 when it was first diagnosed as carpal tunneil syndrome. I've recently begun treatment with Humira after being on Methotrexate, Salazopyrin and anti-inflammatory pills. Unfortunately these caused my to develop Chronic Kidney Disease and Liver fibrosis, causing the need to switch. I am also on Prednisone, although my Rheumatologist wants to phase it out once the Humira is working effectively. 

It's nice to find a forum where other people can share experiences so that I don't feel quite so alone in the struggle, thank you to the founders and members!