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Psoriasis is the result of uncontrolled keratinocyte proliferation, and its pathogenesis involves the dysregulation of the immune system. The interplay among cytokines released by dendritic, Th1, Th2, and Th17 cells leads to the phenotypical manifestations seen in psoriasis. Biological therapies target the cytokine-mediated pathogenesis of psoriasis and have improved patient quality of life. This review will describe the underlying molecular pathophysiology and biologics used to treat psoriasis. A review of the literature was conducted using the PubMed and Google Scholar repositories to investigate the molecular pathogenesis, clinical presentation, and current therapeutics in psoriasis. Plaque psoriasis’, the most prevalent subtype of psoriasis, pathogenesis primarily involves cytokines TNF-α, IL-17, and IL-23. Pustular psoriasis’, an uncommon variant, pathogenesis involves a mutation in IL-36RN. Currently, biological therapeutics targeted at TNF-α, IL-12/IL-23, IL-17, and IL-23/IL-39 are approved for the treatment of moderate to severe psoriasis. More studies need to be performed to elucidate the precise molecular pathology and assess efficacy between biological therapies for psoriasis. Psoriasis is a heterogenous, chronic, systemic inflammatory disease that presents in the skin with multiple types. Recognizing and understanding the underlying molecular pathways and biological therapeutics to treat psoriasis is important in treating this common disease.

Chronic plaque psoriasis is a common debilitating skin disease. The identification of the pathogenic role of the TNF/IL-23/T 17 pathway has enabled the development of targeted therapies used in the clinic today. Particularly, TNF inhibitors have become a benchmark for the treatment of numerous chronic inflammatory diseases such as psoriasis. Although being highly effective in psoriasis treatment, anti-TNFs can themselves induce psoriasis-like skin lesions, a side effect called paradoxical psoriasis. In this review, we provide a comprehensive look at the different cellular and molecular players involved in classical plaque psoriasis and contrast its pathogenesis to paradoxical psoriasis, which is clinically similar but immunologically distinct. Classical psoriasis is a T-cell mediated autoimmune disease driven by TNF, characterised by T-cells memory, and a relapsing disease course. In contrast, paradoxical psoriasis is caused by the absence of TNF and represents an ongoing type-I interferon-driven innate inflammation that fails to elicit T-cell autoimmunity and lacks memory T cell-mediated relapses.

Guselkumab is effective in treating moderate-to-severe plaque psoriasis; however, data from randomized controlled trials in the Chinese population are limited. This study evaluated and verified the efficacy and safety profile of guselkumab in Chinese patients with moderate-to-severe plaque psoriasis. This was a randomized, double-blind, placebo-controlled, phase 4 study. Patients with moderate-to-severe plaque psoriasis were randomized 2:1 to the guselkumab group (guselkumab 100 mg by subcutaneous injection at weeks 0 and 4, then every 8 weeks thereafter through week 44) or the placebo-to-guselkumab group (placebo at weeks 0, 4, and 12, then guselkumab at weeks 16, 20, 28, 36, and 44). Coprimary efficacy endpoints were the proportion of patients achieving Psoriasis Area and Severity Index (PASI) 90 response and the proportion of patients achieving Investigator's Global Assessment (IGA) 0/1 response at week 16. Among the 419 patients screened for eligibility between August 25, 2021, and July 21, 2022, 327 patients were enrolled. All 327 randomized patients (mean age, 41.5 [standard deviation, 12.7] years; 259 [79.2%] men) were treated and included in the analyses. At week 16, 103/110 patients assigned to the placebo group at baseline started guselkumab treatment. Most patients completed the study (210 in guselkumab group and 101 in placebo-to-guselkumab group). Significantly higher proportions of patients with guselkumab achieved PASI 90 (82.4% vs. 2.0%; P <0.001) and IGA score 0/1 (88.8% vs. 7.1%; P <0.001) compared with placebo at week 16. At week 48, response rates were maintained in the guselkumab group (PASI 90: 79.2%; IGA 0/1: 82.4%) and increased in the placebo-to-guselkumab group (PASI 90: 80.2%; IGA 0/1: 86.3%). During the first 16 weeks, the incidence of adverse events was comparable between groups (41.9% guselkumab vs. 39.1% placebo) and the incidence of serious adverse events was low (0.9% vs. 5.5%), respectively. Guselkumab was highly effective and displayed a favorable safety profile for the treatment of moderate-to-severe plaque psoriasis in Chinese patients. ClinicalTrials.gov, NCT04914429.

Dear Editor, Paradoxical eczema (PE) is defined as de novo onset or flare of eczematous lesions during biologic therapy for psoriasis, regardless of atopic diathesis. PE has been reported with anti-tumor necrosis factor (TNF)-α, anti-interleukin (IL)-17, and more recently with anti-IL-23 agents such as risankizumab, tildrakizumab, and guselkumab, with an estimated incidence of 1-3% among psoriatic patients treated with biologics, likely underestimated. Herein, we report the successful use of upadacitinib, an oral selective Janus kinase (JAK)-1 inhibitor approved for both psoriatic arthritis and atopic dermatitis, in the management of a PE induced by guselkumab. [...]

Biologic medications have revolutionized treatment of psoriasis; however, there remains uncertainty in which medications should be used to maximize efficacy based on race/ethnicity. The purpose was to determine if efficacy of biological medications differs based on race/ethnicity. A systematic review identified all clinical trials focused on biologic treatment outcomes from inception of database until March 5th, 2021. Included studies provided data on racial/ethnic differences in biologic skin clearance efficacy using the Psoriasis Area and Severity Index (PASI) and “clear/almost clear” scores. There were 1220 studies identified, and 24 included in the review. The races/ethnicities included were Asian ( n  = 2740), White ( n  = 9745), Black ( n  = 138), and Latino ( n  = 728). Ixekizumab provided the highest “clear/almost clear” score (90.7%, 89.4%) and PASI 75 (98.8%, 96.6%) for Asian and Latino patients, respectively. Guselkumab had the highest “clear/almost clear” score for White (86.8%) patients, while Black patients had highest “clear/almost clear” (75.0%) and PASI 75 (91.7%) scores to brodalumab. Limitations included lack of studies reporting outcome data based on race/ethnicity and lack of patients of color within psoriasis clinical trials. For treatment of plaque psoriasis, there is evidence of differences in efficacy of biologics improving clinical disease severity between different races or ethnicities.

This post-hoc analysis aimed to explore the effect of vunakizumab treatment on detailed dimensions of patient-reported outcomes (PROs) in moderate-to-severe plaque psoriasis patients. This post-hoc analysis derived data from a randomized controlled trial (NCT04839016), which compared the efficacy and safety of vunakizumab with placebo in patients with moderate-to-severe plaque psoriasis. Patients were randomized 2:1 to receive vunakizumab 240 mg or placebo subcutaneously. At week (W)12, patients on placebo were switched to vunakizumab 240 mg. A total of 461 moderate-to-severe plaque psoriasis patients receiving vunakizumab and 229 patients receiving placebo were included in this post-hoc analysis. PROs included the Dermatology Life Quality Index (DLQI), itch numeric rating scale, EuroQol five-dimensional five-level (EQ-5D-5L), and Short Form-36 (SF-36). Items related to anxiety, depression, pruritus, pain, physical function, vitality, and health transitions were extracted from the DLQI, EQ-5D-5L, and SF-36. DLQI and itch numeric rating scale scores at W4, W8, and W12 were lower in the vunakizumab group than in the placebo group (all P < 0.001). EQ-5D-5L and SF-36 mental/physical component scores at W4, W8, and W12 were higher in the vunakizumab group than in the placebo group (all P < 0.001). The mean DLQI (W0: 11.3 ± 6.9, W12: 2.2 ± 3.0, W52: 1.5 ± 3.1) and itch numeric rating scale (W0: 5.6 ± 2.6, W12: 1.6 ± 1.7, W52: 1.0 ± 1.5) scores were decreased from W0 to W52 after vunakizumab treatment. EQ-5D-5L scores (W0: 80.3 ± 16.3, W12: 90.4 ± 8.0, W52: 92.4 ± 8.1) as well as SF-36 mental (W0: 47.8 ± 10.2, W12: 53.7 ± 7.1, W52: 54.5 ± 6.9) and physical (W0: 51.4 ± 6.3, W12: 55.6 ± 4.5, W52: 55.7 ± 5.0) component scores increased from W0 to W52 after vunakizumab treatment. Anxiety, depression, pruritus, and pain were attenuated after vunakizumab treatment. Physical function, vitality, and health transitions were enhanced after vunakizumab treatment. Vunakizumab sustainedly improves overall PROs in Chinese moderate-to-severe plaque psoriasis patients, especially in the dimensions of mental, neurological, and behavioral feelings.

A 77-year-old Chinese male with a 10-year history of plaque psoriasis had recurrent episodes of symmetric hypertrophic verrucous plaques in the lower legs. The patient was monitored for the evolution of the disease over two years before he came to our attention. Because the lesions were resistant to topical glucocorticoids and vitamin D3 at another dermatological center, the patient was treated with secukinumab for one year. However, the verrucous lesions further worsened, and the patient visited the outpatient department of our hospital in March 2023. Treatment with guselkumab was started. It immediately attenuated the plaques of the trunk and limbs. Surprisingly, the verrucous plaques of both legs showed complete resolution in 6 months.

Biologic therapies targeting inflammatory cytokines have transformed the management of plaque psoriasis; however, their use is limited by high cost, parenteral administration, and monitoring requirements. Icotrokinra (JNJ-77242113) is a first-in-class oral peptide that selectively inhibits the interleukin-23 (IL-23) receptor and represents a potential oral alternative. We conducted a systematic review and meta-analysis to evaluate the efficacy and safety of oral icotrokinra in moderate-to-severe plaque psoriasis. A comprehensive search of PubMed, Scopus, Web of Science, and the Cochrane Library was performed to identify randomized controlled trials (RCTs) published up to November 2025. Eligible studies enrolled adolescents or adults with moderate-to-severe plaque psoriasis treated with oral icotrokinra (200 mg once daily) versus placebo. A random-effects model was applied, and dichotomous outcomes were pooled as risk ratios (RRs) with 95% confidence intervals (CIs). Risk of bias was assessed using RoB 2, and trial sequential analysis (TSA) was performed to evaluate the conclusiveness of evidence. Five RCTs comprising 1,951 participants were included. At week 16, icotrokinra significantly improved Investigator's Global Assessment (IGA) 0/1 (RR = 7.27, 95% CI 5.62-9.40) and Psoriasis Area and Severity Index (PASI) 75 responses (RR = 6.70, 95% CI 5.20-8.62) compared with placebo (both < 0.001). Higher levels of skin clearance were also achieved, including PASI 90 (RR = 13.82, 95% CI 8.75-21.84) and PASI 100 (RR = 31.65, 95% CI 12.56-79.76). Significant benefits were observed in scalp-specific disease (ss-IGA; RR = 4.27) and patient-reported outcomes, including complete symptom resolution on the Psoriasis Symptom Scale Diary (RR = 9.76). Adverse event rates did not differ significantly between icotrokinra and placebo, and heterogeneity across outcomes was minimal. TSA indicated that current evidence remains insufficient to confirm definitive conclusions. Oral icotrokinra demonstrates potential efficacy across multiple clinical and patient-reported endpoints with a safety profile comparable to placebo in moderate-to-severe plaque psoriasis. However, TSA indicates that the required information size has not been reached. Therefore, current evidence remains insufficient to draw definitive conclusions. Future RCTs with long-term follow-up are required to confirm these findings. https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=1237937, identifier CRD420251237937.

Plaque psoriasis (PP) is a chronic immune-mediated skin disorder with a genetic basis, characterized by abnormal T-cell responses. This study investigated the role of FOXP3 gene variants rs2280883 and rs3761548 in T-cell regulation through their effects on IL-10 and TGF-β1 cytokine levels and their association with PP risk. A case-control study was conducted, including 101 individuals with PP and 106 healthy controls from the Mexican population. Genotyping of FOXP3 variants was performed using PCR-RFLP, and cytokine levels were measured with ELISA kits. Significant differences in allele and genotype frequencies of the rs2280883 variant were observed between PP patients and controls, suggesting an association with an increased risk of PP. IL-10 levels were found to be elevated in PP patients, regardless of FOXP3 gene variants, indicating that cytokine dysregulation in PP may involve alternative pathways independent of FOXP3-mediated regulatory T-cell (Treg) function. No significant differences were detected in TGF-β1 levels or rs3761548 genotype frequencies across the study groups. In conclusion, the rs2280883 variant in the FOXP3 gene is significantly associated with a higher risk of developing PP in the Mexican population, while dysregulated IL-10 levels suggest a complex cytokine interaction beyond Treg activity.

A literature search on the subject of botulinum toxin treatment in psoriasis found 15 relevant articles, 11 on human subjects and 4 on animal studies. Of the human data, eight were clinical trials and three were single case reports. Seven out of eight clinical trials, all open-label, reported improvement in psoriasis following intradermal or subcutaneous botulinum toxin injections. One double-blind, placebo-controlled study, which used a smaller dose than the open-label studies, did not note a healing effect. Animal studies have shown that injection of botulinum toxins in the skin heals psoriatic skin lesions and can reduce the level of interleukins (ILs) and cytokines as well as inflammatory cells in psoriatic plaques. There is a need for controlled, blinded studies conducted in larger numbers of patients with doses that have shown promise in open-label studies.