Envudeucitinib long term data positioned to set a new standard for plaque psoriasis treatment, delivering highest reported PASI 100 skin clearance among oral therapies.

Quote:

---

Alumis announced topline results from the ongoing ONWARD3 long-term extension (LTE) study. Data confirm envudeucitinib delivered leading skin clearance and the highest reported Psoriasis Area and Severity Index (PASI) 100 response rates among existing and investigational oral therapies. Envudeucitinib is an investigational, next-generation oral TYK2 inhibitor precision-engineered for maximal 24-hour target inhibition.

“Envudeucitinib delivered consistently high rates of skin clearance in the Phase 3 trials, and the long-term data show that the vast majority of patients maintained these strong responses through 48 weeks, with the number of patients achieving completely clear skin continuing to rise over time,” said Dr. Mark Lebwohl, Dean for Clinical Therapeutics at the Icahn School of Medicine at Mount Sinai. “These data, coupled with a consistent safety profile, suggest that envudeucitinib can deliver the durable, reliable disease control physicians and patients are seeking from an oral therapy.”

A total of 1,509 patients entered ONWARD3 from ONWARD1 or ONWARD2, reflecting a robust rollover rate of >85%. A non-responder imputation (NRI) analysis was conducted in 773 of these patients from the envudeucitinib arms who received up to 48 weeks of continuous treatment (24 weeks in ONWARD1/2 and up to 24 weeks in ONWARD3). Topline results include:

• 75% and 54% of patients achieved PASI 90 and PASI 100, respectively
  
• Among patients who entered ONWARD3 with PASI 90 and PASI 100 responses, approximately 90% and 80%, respectively, sustained their skin clearance for the reported duration of the extension study
  

Results from a separate integrated NRI analysis across the ONWARD program (ONWARD1/2 and 3)—evaluating 890 patients originally randomized to envudeucitinib in ONWARD1/2, including those who did not transition into ONWARD3—demonstrated that 66% and 47% of patients who received 48 weeks of envudeucitinib achieved PASI 90 and PASI 100, respectively.

Treatment with envudeucitinib in ONWARD3 continued to be well tolerated, with a safety profile consistent with ONWARD1/2 and no new safety signals observed.

“Far too many people with psoriasis remain undertreated or untreated, and without meaningful skin clearance, this systemic disease continues to limit daily life,” said Leah M. Howard, J.D., President and CEO of the National Psoriasis Foundation. “We are excited for the potential of a new oral therapy that may offer the sustained control patients need to get back to living fully. Restoring those everyday moments is part of what real progress looks like.”

“These long-term data, including the robust 54% PASI 100 response, further validate the strength of envudeucitinib’s precision-engineered design for continuous, maximal TYK2 inhibition and underscore its highly competitive clinical profile,” said Dr. Jörn Drappa, Chief Medical Officer of Alumis. “This level of performance reinforces envudeucitinib’s potential to become a leading oral therapy for moderate-to-severe plaque psoriasis and a 'pipeline-in-a-pill' for immune-mediated diseases driven by IL-23, IL-17, and Type I interferon pathways.”

Alumis plans to present additional results from the ONWARD program at upcoming medical meetings and to submit a New Drug Application (NDA) to the U.S. Food and Drug Administration seeking approval for envudeucitinib for the treatment of moderate-to-severe plaque psoriasis in the fourth quarter of this year. Topline data from the LUMUS Phase 2b trial of envudeucitinib in systemic lupus erythematosus is expected in the third quarter of 2026.

This study looked at the association between psoriasis and overactive bladder among the US population.

Quote:

---

Background:
Both psoriasis and overactive bladder (OAB) are considered systemic conditions that share many inflammatory or immune pathways in the pathogenesis. One previous study found patients with psoriatic arthritis (PsA) reported significantly higher bladder autonomic dysfunction scores compared to controls. But it is currently unclear whether there is an association between psoriasis and OAB.

Objective:
To assess the association between psoriasis and OAB among US population.

Methods:
This cross-sectional, population-based study utilized representative data of US adults aged 20 –59 years from the National Health and Nutrition Examination Survey (NHANES) 2005–2006 and 2009–2014 cycles. The Overactive Bladder Symptom Score (OABSS) was used to define OAB and group its severity into none, mild, moderate, and severe. Weighted logistic regression models were constructed to investigate the association between psoriasis with OAB or OAB severity. Subgroup analyses were performed to identify whether certain factors could influence the relationship. Sensitivity analyses were further conducted to assess the robustness of our findings.

Results:
Among 11,643 participants, 50.95% were male and the mean age at recruitment was 39.67 (11.55) years. The prevalence of psoriasis increased with OAB severity (2.34% [none], 3.01% [mild], 5.13% [moderate], 5.33% [severe]; p = 0.0008). In weighted logistic regression models, psoriasis was significantly associated with OAB (OR = 1.88, 95% CI: 1.32–2.68) after adjusting all covariates, as well as the severity of OAB. Subgroup analyses indicated that the association was stronger among younger participants, males, participants with obesity or hypertension, and those without diabetes or cardiovascular disease (CVD); conversely, no significant associations were observed in participants with pre-diabetes, diabetic mellitus, or CVD. Sensitivity analyses confirmed the robustness of these findings.

Conclusion:
This study demonstrates a significant association between psoriasis and OAB, with a positive correlation to OAB severity, underscoring the need for early identification and management of OAB symptoms in psoriasis patients to improve overall patient outcomes and enhance their quality of life.

Based on efficacy and safety exposure-response analysis results, a dose of 12 mg daily is selected for the Phase III trial. Longer-duration and larger trials of this drug are required to further confirm the efficacy and safety in moderate-to-severe plaque psoriasis patients.

Quote:

---

Background:
Tyrosine kinase 2 (TYK2), a key part of the inflammatory cascade responses, plays an integral role in the pathogenesis of psoriasis. Socrodeucitinib, an oral, TYK2 allosteric inhibitor, selectively inhibits TYK2 cytokine signalling pathways in psoriasis pathogenesis.

Objectives:
To evaluate the efficacy and safety of socrodeucitinib in patients with moderate-to-severe plaque psoriasis.

Methods:
In this phase 2, double-blind, placebo-controlled trial, 125 patients were randomly assigned (1:1:1) to receive socrodeucitinib at 6 mg, 12 mg or placebo orally, once daily, for 12 weeks. The primary endpoint was the proportion of patients with a 75% or greater reduction from the baseline in the Psoriasis Area and Severity Index (PASI) score at week 12.

Results:
At week 12, significantly more patients treated with socrodeucitinib achieved a 75% reduction from baseline in PASI score compared with placebo (28.6% at 6 mg, 72.1% at 12 mg vs. 7.5% for placebo, p < 0.05 and p < 0.001, respectively). At the 12 mg dose, socrodeucitinib resulted in significantly higher response rates compared to placebo, with 46.5% of patients achieving PASI 90 (p < 0.001) and 11.6% achieving PASI 100 (p < 0.05). The treatment of socrodeucitinib also led to significantly higher proportions of patients achieving sPGA responses of 0 or 1 compared to placebo: 33.3% at 6 mg and 65.1% at 12 mg versus 10% for placebo (p < 0.05 and p < 0.001, respectively). Most common adverse events included upper respiratory tract infection which demonstrated a certain dose dependency. Most treatment-related adverse events were mild or moderate, and serious adverse events were infrequent, with no clinically meaningful abnormal trend in laboratory parameters.

Conclusions:
Socrodeucitinib demonstrated significantly greater clearing of psoriasis plaques compared to placebo in patients with moderate-to-severe plaque psoriasis and illustrated a favourable safety and tolerability profile, warranting further investigation in longer-duration and larger trials.

Be careful self treating your psoriasis, here is another "so called" naturel skin treatment found to contain a potent steroid, below is the Health Sciences Authority Singapore (HSA) statement.

Quote:

---

B-LIAN-S HERBAL CREAM 百莲霜草本修复乳膏 (Bai Lian Shuang Cao Ben Xiu Fu Ru Gao)” was marketed as a “Natural Extract Formula” with “zero steroids” to manage psoriasis, eczema, red and itchy skin. However, when HSA tested the product, it was found to contain a potent steroid (clobetasol), and an antifungal agent (miconazole).

A 12-year-old boy had applied it regularly for two months for his eczema. He rapidly gained 6kg over this period and developed stretch marks on his legs. The child's mother came across the product on Facebook and placed an order with the vendor who was based in Malaysia through Facebook Messenger.

HSA’s investigations found that the overseas vendor’s social media account was linked to a local Shopee store. HSA has since worked with the platform administrator to disable the online store, while the relevant Malaysian authorities have also been alerted to the Facebook account.

See a doctor immediately if you are using “B-LIAN-S HERBAL CREAM". Do not stop using these products suddenly on your own as they contain potent steroids. Sudden discontinuation of steroids (including topical steroids which can be absorbed) may cause severe withdrawal symptoms such as fatigue, weakness and low blood pressure, especially when it has been used for more than a few weeks. Children and infants are more susceptible to the effects of steroids and may be at a higher risk of steroid-associated adverse effects.

Takeda’s Zasocitinib Demonstrates Consistent, High Rates of Skin Clearance Across the Body, Including Hard-to-Treat and High-Impact Sites, in Phase 3 Psoriasis Studies.

Quote:

---

Takeda announced new data from the two pivotal Phase 3 studies of zasocitinib (TAK-279), a next-generation, highly selective and potent oral tyrosine kinase 2 (TYK2) inhibitor, in adults with moderate-to-severe plaque psoriasis (PsO) Presented at the 2026 American Academy of Dermatology (AAD) Innovation Academy, these secondary endpoint data show that zasocitinib demonstrated consistent and high rates of skin clearance across hard-to-treat, high-impact sites, including the scalp, nails, palms and soles, compared with placebo.

These data build on the topline results from the Phase 3 randomized, multicenter, double-blind, placebo- and active comparator-controlled LATITUDE PsO 3001 and 3002 studies. In those studies, about 70% of patients treated with zasocitinib achieved static Physician Global Assessment (sPGA) 0/1 (clear or almost clear skin) at week 16, with a significantly greater Psoriasis Area and Severity Index (PASI) 75 response rate seen as early as week 4 and continuing to increase through week 24. The totality of data shows the potential of zasocitinib to deliver rapid and durable skin clearance — even in the hardest-to-treat areas.

“Psoriasis is a complex, heterogeneous disease that can present differently across patients and over time, particularly in high-impact sites that are often difficult to treat,” said Chinwe Ukomadu, MD, PhD, senior vice president and head, Gastrointestinal & Inflammation Therapeutic Area Unit at Takeda. “TYK2 plays a key role in regulating core disease-driving immune pathways, including the IL-23/IL-17 axis and type I interferon, which contribute to variability in disease presentation and treatment response. Our Phase 3 results reinforce the potential of our next-generation TYK2 inhibitor to deliver rapid, durable and consistent skin clearance in a convenient once-daily pill.”

The 3001 and 3002 studies also evaluated patients who had nail psoriasis, or patients with at least moderate scalp or palmoplantar psoriasis, at baseline.2 Results were consistent across the body, including these difficult-to-treat, high-impact sites:

• Scalp: 77% and 74% of patients with scalp psoriasis treated with zasocitinib achieved scalp-specific PGA (ssPGA) 0/1 response versus placebo (7% and 13%; p<0.001) and apremilast (42% and 30%; p<0.001) at week 16.
  
• Palms and soles (palmoplantar): Approximately 70% of patients with palmoplantar psoriasis treated with zasocitinib achieved numerically higher rates of hands and/or feet-specific PGA (hfPGA) 0/1 response (71% and 69%) versus placebo (22% and 10%) and apremilast (44% and 43%) at week 16.
  
• Nails: Zasocitinib also delivered statistically significant improvements in Nail Psoriasis Severity Index (NAPSI) versus placebo at week 16 (p<0.001).
  
• Responses were sustained through week 24 in both studies.
  
• The most common adverse events through week 24 were upper respiratory tract infection, nasopharyngitis and acne, with no new safety signals identified.
  

Takeda plans to submit a New Drug Application for plaque psoriasis with the United States Food and Drug Administration and other regulatory authorities beginning this fiscal year. Zasocitinib is also being evaluated in Phase 3 studies in psoriatic arthritis

In this large cross-sectional study, individuals with psoriasis, despite well-managed skin disease, demonstrated more adverse cardiometabolic profiles and more prevalent myocardial dysfunction by abnormal GLS than controls.

Quote:

---

Background:
Psoriasis is linked to an increased risk of cardiovascular disease, but the impact of psoriasis on cardiac structure and function has been less clear.

Objectives:
To assess cardiac structure, function and cardiometabolic risk factors in individuals with psoriasis compared with matched controls and across psoriasis severity.

Methods:
Cross-sectional analysis of 1010 adults with psoriasis from the prospective PSOCADIA cohort and 1010 age- and sex-matched controls without inflammatory skin disease. Participants underwent clinical assessment and transthoracic echocardiography. Cardiac abnormalities assessed included hypertrophy, valvular disease, systolic and diastolic dysfunction, and myocardial dysfunction defined by global longitudinal strain (GLS) <16%.

Results:
Despite well-managed skin disease, individuals with psoriasis had more prevalent myocardial dysfunction by abnormal GLS (16.7% vs. 6.0%, p < 0.001) compared with controls. This association persisted after adjustment for cardiometabolic risk factors and atherosclerotic cardiovascular disease. Cardiac structure and function were largely similar across psoriasis severity. Higher body mass index and diabetes were independently associated with myocardial dysfunction in psoriasis.

Conclusions:
Individuals with psoriasis, even with well-managed skin disease, exhibit a higher burden of myocardial dysfunction compared with controls, independent of cardiometabolic comorbidity. The prevalence was similar across psoriasis severity, highlighting the importance of cardiovascular assessment in all patients with psoriasis.

Study shows that probiotics can be considered as an adjunct therapy for psoriasis.

Quote:

---

Background:
Psoriasis is a chronic systemic disease with an inflammatory process and systemic involvement that affects the quality of life. Recent research indicates that gut microbiota dysbiosis is common in psoriasis cases, and probiotics have been considered as a potential adjunct therapy; however, the current evidence is limited. The aim of this study was to assess the effects of probiotic supplementation on the severity of psoriasis, treatment satisfaction, and quality of life of patients.

Methods:
Forty-four psoriasis patients between 18 and 70 years old were enrolled in this double-blind, randomized, placebocontrolled trial. They received either topical corticosteroids with a probiotic supplement containing multiple bacterial strains or topical corticosteroids with a placebo for 12 weeks. At the end of the study, changes in the Psoriasis Area and Severity Index (PASI), Dermatology Life Quality Index (DLQI), along with Treatment Satisfaction Questionnaire for Medication (TSQM), and adverse events were assessed.

Results:
Probiotic supplementation resulted in a greater reduction in PASI scores compared to the control group (46% vs. 15%, p = 0.002). At Week 12, the mean DLQI score was significantly lower in the probiotic group (4.364 ± 5.010) as compared to the control group (8.773 ± 6.015, p < 0.001), with 31.8% of probiotic users reporting no impact on quality of life (DLQI score 0-1) versus 0% in controls. The patient satisfaction with treatment was significantly higher in the probiotic group. No adverse effects were reported.

Conclusion:
Probiotics can be recommended as a safe and effective adjunct therapy for psoriasis. They can enhance clinical outcomes, quality of life, and patient satisfaction. Further, larger trials are needed.

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.