This study investigated lifestyle related serum metabolites associated with late onset psoriasis risk and evaluate their predictive potential.

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Background:
Although healthy lifestyle behaviours are associated with a lower risk of psoriasis, the underlying metabolic mechanisms remain unclear.

Objectives:
To investigate lifestyle-related serum metabolites associated with late-onset psoriasis risk and evaluate their predictive potential.

Methods:
We analysed 190,692 participants (aged 38–73) from UK Biobank with complete data on lifestyle and serum metabolites. Healthy lifestyle was assessed based on diet, exercise, smoking and BMI. The association between lifestyle-related metabolites and late-onset psoriasis risk was identified by a sequential analytic strategy that combined the Cox regression and elastic net regression model. A machine learning model was developed to predict psoriasis risk using clinical features, polygenic risk scores (PRS) and critical metabolites.

Results:
During a median of 14.6 years of follow-up, 2114 incident late-onset psoriasis cases were documented among 186,812 participants. Ideal lifestyle factors were significantly associated with reduced disease burden, with BMI showing the highest population attributable fractions (PAF) of 24.1%. We identified 11 of 134 lifestyle-related metabolites that were significantly associated with the risk of late-onset psoriasis. These predominantly mapped to lipid and glucose metabolism pathways, comprising seven lipoprotein subclasses, two ketones, unsaturation degree and phenylalanine. The addition of these metabolites into clinical characteristics and PRS could significantly improve the performance of predicting the risk of late-onset psoriasis (AUC 0.860, 95% CI 0.857–0.863).

Conclusion:
Multiple lifestyle-related serum metabolites are associated with the incidence of late-onset psoriasis, and their integration with traditional clinical features and genetic susceptibility shows promise in enhancing the predictive accuracy of late-onset psoriasis using a machine learning–based model.

Transition from psoriasis to psoriatic arthritis was associated with distinct alterations of the peripheral blood T cell compartment with Tc17 cells exhibiting the greatest discriminatory power.

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Objective:
Cellular mechanisms driving transition from psoriasis to psoriatic arthritis have remained largely elusive. Thus, we investigated changes within the peripheral blood T cell compartment associated with the transition phase.

Methods:
In an observational study, 116 patients were examined and categorized into subgroups including psoriasis with at least one risk factor for transition to psoriatic arthritis, subclinical psoriatic arthritis according to EULAR taskforce recommendations from 2023, and definitive psoriatic arthritis meeting the CASPAR criteria. Demographic and clinical characteristics of patient subgroups were analyzed. Deep T cell phenotyping using multicolor flow cytometry and machine learning techniques were applied.

Results:
Overlapping T cell endotypes were found among patients with subclinical psoriatic arthritis exhibiting the most notable divergence from the others. Frequencies of effector memory CD4+ T (TEM) cells, T helper 17 (Th17) and T cytotoxic 17 (Tc17) cells differed between psoriasis with at least one risk factor for transition, subclinical psoriatic arthritis and psoriatic arthritis. Transition-associated changes of Tc17 cell frequencies were confirmed by machine learning-assisted unsupervised clustering analysis. Moreover, patients with enthesitis could be distinguished from those without, with Tc17 cells being the main distinctive feature.

Conclusion:
Transition from psoriasis to psoriatic arthritis was associated with distinct alterations of the peripheral blood T cell compartment with Tc17 cells exhibiting the greatest discriminatory power. These findings provide insight into pathomechanisms driving disease progression during transition from psoriasis to psoriatic arthritis and identify Tc17 cells as foremost novel potential therapeutic target for the prevention of transition.

Hello !
Yes im still alive...
After 6 years of satisfaction with Stelara , this morning i have started Uzpruvo.
The license for Stelara is expired in Czech Republic and my Doctor has given me Bio-similar Uzpruvo.
Have you experience with this new bio treatment?
I hope that it will work well as Stelara.
Fingers crossed

Fibroblasts comprise the main cell type of connective tissue, possessing a spindle-shaped morphology, and produce and maintain the extracellular matrix responsible for the structural integrity of tissues and organs and could soon be used to treat psoriasis.

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FibroBiologics announced positive IND-enabling updates from its psoriasis research program demonstrating the potential of human dermal fibroblast (HDF) spheroids as a novel therapeutic approach for chronic-relapse psoriasis.

Psoriasis is a serious autoimmune condition affecting over eight million adults in the United States. In many cases, it progresses to psoriatic arthritis, significantly impacting quality of life. FibroBiologics is focused on harnessing fibroblast science to develop therapies that are not just incremental improvements, but durable, scalable solutions for patients.

“In an acute psoriasis model, a single administration of HDF spheroids matched the efficacy of multiple doses of an anti-IL-23 monoclonal antibody. Now, in a chronic-relapse model, that same single treatment has been shown to significantly reduce disease recurrence,” said Hamid Khoja, Ph.D., Chief Scientific Officer of FibroBiologics.

The company is continuing to expand its research, including exploring repeated dosing regimens, systemic and local cytokine profiling, and histopathological assessments of skin lesions. These efforts are designed to deepen understanding of the mechanisms at work and strengthen the foundation for clinical advancement.

“These IND-enabling results are a pivotal milestone on our path to building a category-defining company in regenerative medicine,” said Pete O’Heeron, Founder and Chief Executive Officer at FibroBiologics. “Chronic inflammatory diseases represent a massive, underserved market, and the ability to address them at scale is a generational opportunity. At FibroBiologics, we’re relentlessly focused on durability, safety, and reproducibility—because those are the levers that unlock scalability and market leadership. The breakthroughs our scientists achieve strengthen the evidence base and bring us closer to creating long-term value for both patients and shareholders.”

FibroBiologics is now evaluating whether a single HDF spheroid treatment can be developed to deliver long-term protection against psoriasis relapse, an outcome that would represent not just progress, but a step-change in how chronic inflammatory diseases are treated.

Individuals with anxiety + smoking or anxiety + hypertension have a higher risk of developing psoriasis.

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Background:
Psoriasis is linked with an elevated risk of anxiety disorders, and there may be a temporal relationship between the two. However, the association between anxiety status and its duration with psoriasis is unclear.

Objectives:
The present work aimed to figure out the association between anxiety and the risk of psoriasis.

Methods:
Data from the National Health and Nutrition Examination Survey (NHANES) 2009–2012 were used. Anxiety state and days of anxiety were applied as the independent variables, and psoriasis as the dependent variable. Weighted logistic regression was employed to analyze the connection between the state and days of anxiety with psoriasis. Restricted cubic spline (RCS) was further utilized to dig out the nonlinear association between days of anxiety and psoriasis. By using weighted logistic regression to further explore the correlation between the combination of anxiety and common cardiovascular risk factors (smoking, hypertension, CVD events) and the risk of psoriasis. Finally, a weighted logistic regression model was constructed for different genders and alcohol consumption subgroups to explore the association between anxiety status and anxiety days and psoriasis and to evaluate the differences in association among different groups.

Results:
A total of 8888 participants were included in this project, among whom 265 cases (3.1%) were psoriasis patients. Through the weighted logistics regression model, we observed a significant positive correlation between anxiety (OR: 1.439, 95% CI: 1.008–2.053, p = 0.030), number of days with anxiety (OR: 1.018, 95% CI: 1.002–1.033, p = 0.014), and the risk of psoriasis in patients. The RCS curve results indicated a linear positive correlation between anxiety days and the risk of psoriasis (p-nonlinear = 0.162). The results of the joint analysis demonstrated that anxiety−/smoking+ (OR: 1.800, 95% CI: 1.160–2.800, p = 0.011), anxiety+/smoking+ (OR: 2.720, 95% CI: 1.430–5.190, p = 0.004), anxiety+/hypertension+ (OR: 2.010, 95% CI: 1.200–3.370, p = 0.011), anxiety−/CVD event+ (OR: 1.740, 95% CI: 1.080–2.820, p = 0.026), and anxiety+/CVD event− (OR:1.470, 95% CI: 1.000–2.150, p = 0.047) were linked with a significantly elevated risk of psoriasis. The subgroup analysis results showed that women (especially those who drink alcohol) were more sensitive to anxiety status and duration, and the association between increased anxiety days and increased risk of psoriasis was more significant, while no similar significant association was observed in men.

Conclusion:
Anxiety and the number of days with anxiety are positively linked with the risk of psoriasis. Individuals with anxiety+/smoking+ or anxiety+/hypertension+ have a higher risk of developing psoriasis. We recommended that, in the prevention and management of psoriasis, individuals need to cope with stress to alleviate anxiety symptoms and try not to smoke. Women should pay special attention to regulating anxiety while drinking alcohol and monitoring blood pressure and cardiovascular health regularly.

This study looked at  the efficacy and safety of Ilumetri / Ilumya (tildrakizumab) in a cohort of patients with moderate-to-severe psoriasis and a previous or current history of neoplasia.

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Background:
Tildrakizumab has demonstrated high efficacy and a good long-term safety profile, including low malignancy rates, in Phase III trials with 5-year extension. Despite these data, the real-world evidence on patients with psoriasis and a history of cancer is limited.

Objectives:
To assess the efficacy and safety of tildrakizumab in a cohort of patients with moderate-to-severe psoriasis and a previous or current history of neoplasia.

Methods:
We conducted a retrospective, observational, multicentre study across 27 Spanish dermatology departments. All patients had moderate-to-severe plaque psoriasis and a prior history of an active neoplasia at the time of initiating tildrakizumab treatment.

Results:
Forty-eight patients with a mean follow-up period of 50 weeks after initiation of tildrakizumab were included. At Week 24, 82.4% of evaluable patients achieved a Psoriasis Area and Severity Index (PASI) score < 3. By Week 48, 80.0% achieved PASI < 1 and 50.0% reached PASI 0. Twelve patients (25%) began treatment within one year of cancer diagnosis, and four patients started tildrakizumab prior to cancer detection and did not stop treatment. Of the remaining 32, they started tildrakizumab an average of 4.95 years after the cancer diagnosis. Seven patients had active neoplasia at baseline. Overall, 95.8% of the patients did not experience recurrence or worsening of the neoplasia. No adverse events related to tildrakizumab were reported. The cancer state was not considered affected by the psoriasis therapy in any of the cases.

Conclusion:
The treatment of moderate to severe psoriasis with tildrakizumab was an effective option, with a safe profile in patients with a history of cancer.

Hi All

Started Pyzchiva on 18th June 2025, thought I would wait to see how it
was going before posting.

Well maybe a coincidence but had a slight headache on and off for about 5
days afterwards.

I have had pain in one shoulder , slightly progressing down arm some days
for about 4 weeks.  I sometimes suffer neck pain etc and blame it on pillows,
lifting etc.  Slight pain in one knee.  I have never been diagnosed with any type of arthritis,
I suffer from aches and pains but put that down to age! this time the pain is not for
going away, I await next jag to see if there is any difference.  I do not have
any swelling of fingers etc.

Skin remains the same as when taking Stelara, small bit appears on elbow and
goes again.  Flakes in ear remain the same.

No other issues or notable side effects.

Due next dose this week and will keep this thread updated.

Hope you are all well.

Angie  Wave

World Health Organization (WHO) has updated it's list of essential medicines for psoriasis.

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The Expert Committee considered that the inclusion of effective and safe biologics for psoriasis on the EML would address an important public health need and support global advocacy efforts to reduce the global burden of psoriasis, especially in low and middle-income countries. The Committee acknowledged that a large number of biologic disease-modifying medicines for psoriasis are available and the need to prioritize the most effective, tolerable and affordable options.

The Expert Committee recommended the inclusion of adalimumab and ustekinumab on the complementary list of the EML and EMLc for the treatment of adults and children with moderate-to-severe psoriasis, based on evidence of favourable efficacy and safety, as second line treatment alternatives. Listing complements the non-biologic therapies used in first line for psoriasis currently listed on the Model Lists (e.g. topical corticosteroids, systemic methotrexate).

The Committee considered that adalimumab and other tumour necrosis factor alpha inhibitors could be considered therapeutic alternatives to each other in most clinical scenarios and that including multiple within-class alternatives on the Model Lists could support greater competition to lower prices. The Committee therefore recommended adalimumab be listed with a square box as the class representative with certolizumab pegol, etanercept and infliximab as specified therapeutic alternatives.

The Committee recommended inclusion of ustekinumab in addition to adalimumab because of some advantages ustekinumab has over adalimumab and other tumour necrosis factor alpha inhibitors. When considering the administration schedule, adalimumab is administered every two weeks while ustekinumab is administered every 12 weeks. Less frequent injections are more convenient, with reduced disruption to daily life for patients and reduced burden and costs for health systems. Ustekinumab is preferred to adalimumab in patients with heart disease and in settings where tuberculosis is endemic as it is associated with a lower risk of tuberculosis reactivation. While ustekinumab is currently more highly priced than adalimumab, biosimilars are becoming increasingly available. For ustekinumab, the Committee did not recommend listing with a square box. The Committee acknowledged the data supporting similar or better effectiveness of other monoclonal antibodies targeting IL-12 and IL-23 (e.g. guselkumab, risankizumab and tildrakizumab) but considered the alternatives to have less supportive evidence, biosimilars are not yet available, and there is no information regarding their costs in most jurisdictions which were assumed to be higher than ustekinumab.

Quality-assured biosimilars are recommended as therapeutic alternatives of both adalimumab (and therapeutic alternatives) and ustekinumab.

University of Queensland Australia researchers have been the first in the world to successfully grow fully functioning human skin in a laboratory that could one day help find better treatments for psoriasis.

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Dr Shafiee said.

“This is the most life-like skin model that’s been developed anywhere in the world and will allow us to study diseases and test treatments more accurately”

“It developed just like natural human skin, with layers, hair follicles, pigmentation, appendage patterning, nerves, and most importantly, its own blood supply”

“This skin model will enable us to further progress those treatments, along with wound healing, regenerative medicine and precision dermatology"

“Skin disorders can be difficult to treat, and it’s a real breakthrough to be able to provide hope for people living with chronic conditions such as psoriasis"

Investigating the effectiveness and safety of psoriasis treatment after the failure of initial biologic therapy, particularly when patients switch to a second biologic.

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Question: 
What is the effectiveness and safety of interclass biopharmaceutical switching in psoriasis treatment?

Findings:
This systematic review and meta-analysis of 24 randomized clinical trials including 12 661 patients found that interclass biopharmaceutical switching demonstrated faster short-term and more stable long-term effectiveness. Switching from anti−tumor necrosis factor (TNF)-α agents to anti−interleukin (IL)-23p19 agents and from anti−IL-12/23p40 agents to anti−IL-23p19 agents led to significantly improved effectiveness; however, switching was associated with an increased risk of infection that was higher when switching from anti−TNF-α agents to anti−IL-23p19, anti−IL-17A, and anti−IL-12/23p40 agents.

Meaning: 
These findings indicate that clinicians may consider biopharmaceutical switching to reduce costs, enhance effectiveness, and minimize adverse events; however, future studies are needed to determine the long-term safety of biologics that target different pathways in clinical practice.

Johnson & Johnson files with U.S. Food and Drug Administration (FDA) to include new evidence in Tremfya (guselkumab) label as the only IL-23 inhibitor to demonstrate significant inhibition of joint structural damage in active psoriatic arthritis.

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Johnson & Johnson (NYSE: JNJ) today announced the submission of a supplemental Biologics License Application (sBLA) to the U.S. Food and Drug Administration (FDA) seeking approval to include new evidence in the TREMFYA® (guselkumab) label for the inhibition of progression of structural damage in adults with active psoriatic arthritis (PsA).

The submission is supported by the Phase 3b APEX study in patients with active PsA, which achieved both its primary endpoint of reducing joint symptoms (ACR20) and its major secondary endpoint of inhibited progression of structural damage as measured by change in the modified van der Heijde-Sharp (vdH-S) score at 24 weeks, compared to placebo in bio-naïve patients.

Data from the APEX study were consistent with the well-established safety profile of TREMFYA®. Additional data will be presented at future medical meetings.

TREMFYA® is the first and only fully-human, dual-acting monoclonal antibody approved to treat PsA that blocks IL-23 while also binding to CD64, a receptor on cells that produce IL-23. IL-23 is a cytokine secreted by activated monocyte/macrophages and dendritic cells that is known to be a driver of immune-mediated diseases including active PsA.

Bath-PUVA therapy involved immersion in water at 37°C containing 8-methoxypsoralen bath salts at a concentration of 0.0001% for 15 min, followed by immediate ultraviolet A (UVA) irradiation.

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Background/Purpose:
While biologics and small-molecule inhibitors are first-line systemic treatments for psoriasis, phototherapy remains an alternative for patients unable to access these treatments because of medical or financial constraints. Narrow-band ultraviolet B (NB-UVB) is effective for localized psoriasis but less so for extensive disease. To address this limitation, bathwater delivery of psoralen plus ultraviolet A (bath-PUVA) was introduced in 2004. This study evaluates the efficacy, safety, and patient characteristics associated with bath-PUVA therapy in a large cohort.

Methods:
This retrospective analysis included 229 patients (180 males, 49 females) treated with bath-PUVA from 2004 to September 2021. Baseline characteristics and treatment outcomes were assessed using the psoriasis area and severity index (PASI). Statistical analyses examined relationships between treatment outcomes and factors, including baseline PASI, body mass index (BMI), and smoking status.

Results:
The mean baseline PASI score was 24.9. Bath-PUVA achieved PASI 75 in 80.4% of patients, PASI 90 in 44.1%, and PASI 100 in 2.6%, with efficacy comparable to biologics. Patients achieving PASI 90 had significantly higher baseline PASI scores (p = 0.005), while the number of irradiations required did not differ (p = 0.692). Higher baseline PASI scores correlated with elevated BMI (p = 0.002), but BMI did not influence improvement rates (p = 0.094). Smokers had significantly higher baseline PASI scores (p = 0.004) compared with non-smokers, yet smoking status did not affect improvement rates (p = 0.862).

Conclusion:
Bath-PUVA demonstrates efficacy comparable with biologics for psoriasis, regardless of BMI or smoking status. This analysis supports its use as an effective and accessible treatment option for patients with extensive disease.

The aim of this pilot study was to assess the effect of repeated dithranol applications on aspects of histopathologic features of psoriasis.

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Background:
There are only limited histomorphological data on the response of psoriatic skin lesions to topical dithranol. In vivo reflectance confocal microscopy (RCM) in psoriatic skin is highly correlated with histopathological findings and allows non-invasive monitoring of treatment effects on a cellular level.

Patients and Methods:
Prospective, single-center pilot study at a university-based clinic of dermatology between January 1st and August 30th, 2016. Psoriatic lesions of 20 patients receiving dithranol treatment were assessed by RCM at baseline, day 4 and 8 of treatment.

Results:
RCM measurements of psoriatic lesions receiving dithranol treatment revealed epidermal histomorphological changes with a strong median reduction of baseline hyperkeratosis by 45.0% (p < 0.001), acanthosis by 38.2% (p < 0.001), and epidermal thickness by 66.5% (p < 0.001) from baseline until day 8. Moreover, semiquantitative measurements of parakeratosis also showed a significant reduction until day 8 (p < 0.001). Correspondingly, RCM revealed dermal histomorphological changes with a decrease in diameter of dermal papillae by 32.1% (p < 0.001), decrease in diameter of papillary vessels by 16.9% (p = 0.002) and a strong semiquantitative reduction of the inflammatory infiltrate (p < 0.001).

Conclusions:
Results from our pilot study indicate that topical dithranol treatment of psoriatic lesions may induce a rapid and marked reduction of pathologic epidermal and dermal RCM features.

Johnson & Johnson seeks first icotrokinra U.S. FDA approval aiming to revolutionise treatment paradigm for adults and adolescents with plaque psoriasis.

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Johnson & Johnson (NYSE: JNJ) today announced the submission of a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) seeking the first approval of icotrokinra, a first-in-class investigational targeted oral peptide that selectively blocks the IL-23 receptor for the treatment of adults and pediatric patients 12 years of age and older with moderate to severe plaque psoriasis (PsO). Icotrokinra is uniquely designed to block the IL-23 receptor, which underpins the inflammatory response in plaque PsO and offers potential in other IL-23-mediated diseases.

The application included data from four pivotal Phase 3 studies conducted as part of the ICONIC clinical development program, including ICONIC-LEAD, ICONIC-TOTAL and ICONIC-ADVANCE 1 & ICONIC-ADVANCE 2. Treatment with icotrokinra met all primary and co-primary endpoints across the development program among adults and pediatric patients 12 years of age and older with moderate-to-severe plaque PsO, demonstrating significant skin clearance and a favorable safety profile in a once-daily pill. Results from the ICONIC-ADVANCE 1 & 2 studies show icotrokinra achieved co-primary endpoints and showed superiority to deucravacitinib in moderate-to-severe plaque PsO. Across all studies, pooled safety data showed a similar proportion of patients experienced adverse events (AEs) between icotrokinra (49.1%) and placebo (51.9%) groups, with no new safety signals identified to date.

“The rapid patient enrollment across our ICONIC clinical program underscores the unmet need for an advanced plaque psoriasis treatment that meaningfully addresses their needs and preferences,” said Liza O’Dowd, MD, Vice President, Johnson & Johnson Innovative Medicine. “Given the breadth and depth of our studies, along with the robust clinical results reported to date, we are confident that icotrokinra has the potential to transform how physicians and patients think about plaque psoriasis care, establishing a new standard in the treatment of this immune-mediated disease.”

Johnson & Johnson has also initiated the Phase 3 ICONIC-ASCENDf study, the first-ever head-to-head study seeking to demonstrate the superiority of an oral pill, icotrokinra, compared to an injectable biologic, ustekinumab, representing an important step forward in psoriasis research.

Bristol Myers Squibb today announced that the U.S. Food and Drug Administration and The European Medicines Agency has accepted for review the supplemental new drug application (sNDA) for Sotyktu (deucravacitinib) for the treatment of adults with active psoriatic arthritis.

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The FDA has assigned a Prescription Drug User Fee Act (PDUFA) goal date of March 6, 2026. This latest regulatory milestone is in addition to the sNDA acceptances by China’s Center for Drug Evaluation of National Medical Products Administration and Japan's Ministry of Health, Labour and Welfare for Sotyktu for the treatment of adults with active psoriatic arthritis. The European Medicines Agency has also validated Bristol Myers Squibb's Type II variation application to expand the indication for Sotyktu to include this disease.

“There is a significant need for additional oral treatments for individuals living with psoriatic arthritis, and today’s announcement brings us one step closer to bringing Sotyktu to these patients,” said Roland Chen, MD, Senior Vice President, Bristol Myers Squibb. “We are eager to continue conversations with the FDA and other global regulatory bodies with the goal of including Sotyktu as a differentiated, first-line, advanced systemic treatment option for psoriatic arthritis, while we pioneer research of this novel molecule in other severe rheumatic conditions.”

Sotyktu received approval from the FDA in 2022 for the treatment of adults with moderate-to-severe plaque psoriasis who are candidates for systemic therapy or phototherapy. Since then, Sotyktu has earned approvals for this indication from multiple global health authorities and demonstrated durable efficacy and a consistent safety profile over more than 20,000 patient-years of experience.

Sotyktu, an oral, selective tyrosine kinase 2 (TYK2) inhibitor, has the potential to be the first TYK2 inhibitor for the treatment of psoriatic arthritis.

The regulatory applications are based on positive results from the pivotal POETYK PsA-1 and POETYK PsA-2 trials, which evaluated the efficacy and safety of Sotyktu in adults with active psoriatic arthritis. Both trials met their primary endpoint, with a significantly greater proportion of Sotyktu-treated patients achieving ACR20 response (at least a 20 percent improvement in signs and symptoms of disease) after 16 weeks of treatment compared with placebo. Additional data from POETYK PsA-2 reported outcomes through 52 weeks of treatment and demonstrated that clinical response improved and was maintained from Weeks 16 to 52.

The overall safety profile of Sotyktu through 16 weeks of treatment in the POETYK PsA-1 and POETYK PsA-2 trials was consistent with that established in a Phase 2 PsA clinical trial and Phase 3 moderate-to-severe plaque psoriasis clinical trials; no new safety signals were observed.

Sun Pharma today announced top-line results from two Phase 3 clinical studies evaluating the efficacy and safety of Ilumya / Ilumetri (tildrakizumab) 100 mg administered over 24 weeks for treatment of active psoriatic arthritis.

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Treatment with tildrakizumab 100 mg resulted in greater improvements in PsA signs and symptoms at week 24 compared to treatment with placebo.

Both the INSPIRE-1 and INSPIRE-2 studies achieved the primary endpoint, with a higher proportion of patients in the INSPIRE-1 and INSPIRE-2 studies treated with tildrakizumab achieving ACR20 responses at week 24, compared to those receiving placebo (p < 0.05).

"We are excited to share that both the INSPIRE-1 and INSPIRE-2 clinical trials have successfully met their primary endpoints. These top-line results reinforce the therapeutic potential of tildrakizumab as a treatment option for patients with active psoriatic arthritis. We extend our sincere gratitude to the patients, healthcare professionals and administrators whose contributions made the studies possible. We look forward to sharing the complete clinical data in the near future"

Safety data in the studies was consistent with the well-documented safety profile of tildrakizumab, which is approved for the treatment of adults with moderate-to-severe plaque psoriasis who are candidates for systemic therapy or
phototherapy.

No new safety signals were identified in the INSPIRE-1 and INSPIRE-2 studies. Findings from the INSPIRE studies will be presented at upcoming medical conferences and published in a peer-reviewed medical journal. Use of tildrakizumab 100 mg in psoriatic arthritis is not approved, and its safety and efficacy have not been evaluated by regulatory authority

ORKA-001 is a novel, subcutaneously administered, half-life extended monoclonal antibody targeting IL-23p19 that has the potential to be dosed just once or twice a year in patients with psoriasis.

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Oruka Therapeutics a biotechnology company developing novel biologics designed to set a new standard for the treatment of chronic skin diseases including plaque psoriasis, today announced that the U.S. FDA cleared its investigational new drug (IND) application for its Phase 2a trial of ORKA-001 (the Company’s long-acting anti-IL-23p19 antibody) in moderate-to-severe psoriasis, called EVERLAST-A.

“We’re thrilled by this rapid progress into Phase 2 development, and very excited to start our first psoriasis study,” said Lawrence Klein, PhD, CEO of Oruka. “We think that ORKA-001 can redefine the standard of care in this important disease with potential for once per year dosing, off-treatment remissions and higher rates of disease clearance.”

The U.S. FDA cleared the Company’s IND submission to initiate EVERLAST-A. EVERLAST-A is a randomized, double-blind, placebo-controlled Phase 2a trial designed to evaluate the safety and efficacy of a single dose level of ORKA-001 in moderate-to-severe psoriasis patients. EVERLAST-A will enroll approximately 80 patients, randomized 3:1 to receive ORKA-001 or matching placebo. The primary endpoint is PASI 100 at Week 16. ORKA-001 exposures are expected to match or exceed exposures in the KNOCKOUT study, providing a definitive test of whether higher exposures of an anti-IL-23p19 antibody can lead to greater efficacy. At Week 28, patients who have achieved PASI 100, or completely clear skin, will be randomized 2:1 to either an arm where they do not receive another dose until disease recurs or ORKA-001 every six months. This “no-dose” arm will provide evidence for both yearly dosing and the potential for extended off-treatment remissions. Patients who have not yet achieved PASI 100 at Week 28 will receive ORKA-001 every six months.

"We have made great strides in our ability to treat psoriatic disease, but many patients are still seeking improved treatment options. I’m excited about EVERLAST-A and the potential that ORKA-001 could enable long dosing intervals and greater efficacy than current IL-23 inhibiting medications. There is evidence now that these improvements could be within reach, and they would be a significant step forward for both patients and the field,”

This study demonstrates the deletion of the m6A writer Mettl3 in mouse macrophages mitigates imiquimod (IMQ)-induced psoriasis-like inflammation.

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Impaired N6-methyladenosine (m6A) modification has been implicated in regulating various inflammatory diseases, but its role in psoriasis remains unclear.

Here, m6A modification and its methyltransferase METTL3 are revealed to be upregulated in psoriatic macrophages, while the demethylase ALKBH5 is downregulated. Conditional knockout of Mettl3 in macrophages alleviated psoriasis-like symptoms in mice, whereas knockout of Alkbh5 exacerbated them.

Both in vivo and in vitro, Mettl3 deficiency inhibited IMQ-induced M1 macrophage polarization, while Alkbh5 deficiency promoted M1 polarization. The regulation of macrophage polarization by m6A is likely mediated by targeting Slc15a3. SLC15A3 enhances the recruitment of TASL, a recently identified endolysosomal IRF5 adaptor, which functions similarly to the IRF3 adaptors STING and MAVS at the endoplasmic reticulum (ER) and mitochondria, respectively, to augment IRF5 signaling via SLC15A4.

The findings underscore the critical role of m6A RNA modification in psoriasis pathogenesis and unveil a novel regulatory mechanism of TASL-IRF5 signaling through m6A modification, suggesting potential new therapeutic targets for psoriasis treatment.

Itching sensation and elevated interleukin-31 levels as potential indicators of exceptional response to biologics in patients with moderate-to-severe psoriasis.

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Although the introduction of biologics has significantly changed the psoriasis treatment paradigm, predicting which patients will respond favourably to biologics remains a challenge.

Our study aimed to retrospectively investigate the characteristics of ‘exceptional responders’ (ERs), that is, patients who achieve a Psoriasis Area and Severity Index (PASI) of 100 between weeks 16 and 28 of their initial evaluation period.

We conducted a retrospective analysis of the electronic medical records and clinical photographs of 139 patients with psoriasis. Demographic and clinical characteristics of the patients were collected and analysed. Peripheral blood samples previously obtained from consenting individuals (n = 10 for each group) were used to compare the serum concentrations of interleukin-31 (IL-31), lipocalin-2 (LCN2) and chemokine ligand 2 (CCL2), between ERs and non-ERs.

We observed no significant differences in nail involvement, arthralgia, mean body mass index, or baseline PASI between ERs and non-ERs. Notably, the occurrence of itching was significantly higher in the ER group than in the non-ER group. The IL-31 concentration displayed a concomitant increase with the intensity of itching and was significantly higher in ERs than in non-ERs prior to the initiation of biologics.

After treatment, a significant decrease in IL-31 levels was observed in the ER group but not in the non-ER group. While both LCN2 and CCL2 levels decreased significantly after treatment in both groups, they did not exhibit clear distinctions that could differentiate between ERs and non-ERs. Baseline IL-31, combined with itch intensity, discriminated ERs from non-ERs.

Clinicians should recognise that patients presenting with pruritus and high serum IL-31 levels may respond exceptionally well to biological agents, whereas those without pruritus and with lower IL-31 levels tend to have a more subtle response.

This study demonstrates that poor cardiovascular-kidney-metabolic (CKM) health was significantly associated with an increased risk of psoriasis.

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Background:
Limited evidence exists concerning the relationship between cardiovascular–kidney–metabolic (CKM) health and the incidence and prognosis of psoriasis.

Objective:
This study aimed to evaluate the associations between CKM status, genetic risk and the risk of developing psoriasis, as well as to examine the impact of CKM syndrome on life expectancy in patients with psoriasis.

Method:
This prospective cohort study included 392,454 participants free of psoriasis from the UK Biobank. CKM syndrome was defined by the presence of metabolic risk factors, chronic kidney disease and cardiovascular disease, categorized into five stages (0–4). The genetic risk of psoriasis was assessed using a polygenic risk score. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) for the incident risk of psoriasis.

Results:
Compared to participants in stage 0, the multivariable-adjusted HRs (95% CIs) for developing psoriasis in individuals with CKM stages 1, 2, 3 and 4 were 1.21 (1.06–1.38), 1.38 (1.24–1.55), 1.64 (1.42–1.91) and 1.72 (1.47–2.01), respectively. Joint association analyses revealed that participants with CKM stage 4 and high genetic risk had the highest risk of psoriasis compared to those at stage 0 with low genetic risk (HR = 2.82, 95% CI: 2.28–3.49). Notably, there was a significant positive additive interaction between advanced CKM stages and high genetic risk in the development of psoriasis (RERI = 0.82, 95% CI: 0.35–1.32). Additionally, within the psoriasis population, advanced CKM stage (stage 4) was associated with a greater reduction in life expectancy (2.03 years, 95% CI: 0.25–3.81 years).

Conclusions:
Poor CKM health was significantly associated with a higher risk of psoriasis in midlife and older adults, particularly among those with high genetic risk and was further linked to decreased life expectancy among patients with psoriasis.