Psoriasis Area And Severity Index Research Articles

Psoriasis is a chronic inflammatory skin disease whose pathogenesis involves not only cutaneous inflammation but also intestinal dysbiosis and oxidative stress (OxS). Monoclonal antibodies targeting interleukin (IL)-17 and IL-23 have demonstrated significant immunomodulatory effects; however, their impact on systemic parameters requires further investigation. We conducted a study on 33 patients with plaque psoriasis treated with anti-IL-17 or anti-IL-23 monoclonal antibodies. Dermatological parameters (Psoriasis Area and Severity Index (PASI) and Dermatology Life Quality Index (DLQI)), biomarkers of intestinal dysbiosis (trimethylamine-N-oxide (TMAO)) and OxS (reactive oxygen metabolites (d-ROMs) and oxidized LDL (oxLDL)) were evaluated. Anthropometric, metabolic, and adipose-derived hormonal parameters (adipokines) were also monitored. After 16 weeks of therapy, significant improvements were observed in PASI and DLQI scores (p < 0.001). TMAO levels were significantly reduced (p = 0.02), as were d-ROMs and oxLDL (p < 0.001). No significant changes were found in weight, body mass index, lipid profile, or adipokine levels (visfatin, leptin and adiponectin). Our data indicate that monoclonal antibody therapy not only improves psoriasis severity but also exerts beneficial effects on systemic biomarkers of dysbiosis and OxS, independent of metabolic or hormonal changes. These findings suggest a systemic mechanism of action, supporting a multifactorial therapeutic effect with potential implications for the prevention of cardiovascular risk.

Plaque psoriasis: It is the commonest type of psoriasis, a chronic, immune mediated and genetic based dermatoses, characterizing by redness, thickness and scaly plaques occurring most commonly on the elbows, knees, scalp, and lower back, but any skin surface can be involved, has a major impact on quality of life. D3 or cholecalciferol: A fat soluble vitamin that has many important and vital roles for normal body physiological activities. Certain types of food in addition to dietary supplements and exposure to sun UVB radiation are sources for this vitamin. Clobetasol: It is the perfect of topical corticosteroids, works as anti-inflammatory, anti-pruritic and vasoconstrictive properties, and reduces the activity of immune system and is currently used to treat hyperproliferation or inflammatory for plaque psoriasis. Salicylic acid: It is a keratolytic agent, acted as a scale pulley, helpful to smoothing and eradicate psoriasis scales. Complete Blood Count (CBC and Erythrocytes Sedimentation Rate (ESR). Psoriasis Area and Severity Index (PASI): is a widely used appliance in psoriasis tribunals that judges and grades the sternness of psoriatic lesions and the patient’s reaction to treatment. Aim: To explore the impact of adding urea to salicylic acid and clobetasol combination in improving their antipsoriatic activity in patients with mild to moderate plaque psoriasis, to control signs and symptoms of this disease and to improve the quality of life. Materials and Method: This study includes 100 samples divided two groups of plaque psoriasis patients whose severity of psoriasis ranges from mild to moderate. A formula containing clobetasol and salicylic acid is given to the first group of plaque psoriasis patients (Control), and a formula containing clobetasol and salicylic acid in addition to Vitamin D3 is given to the second group of patient’s plaque psoriasis (case). The levels of lymphocytes, erythrocytes sedimentation rate (ESR) was measured, and the Score was calculated for both groups and compared with the time and drug response rate for both groups. Results: The study included 100 psoriatic patients divided to 63 were female and 37 were male. The ages of the patients ranged from 20-65 years. The WBC, lymphocytes, ESR and PASI mark were resolute before the treatment for control and case groups to be non-significant (P> 0.03, 0.09, 0.52 and 0.32). WBC and Lymphocytes, ESR and PASI score values were lower after adding vitamin D3 to the regimen of salicylic acid and clobetasol than without adding D3 to be significant (P> 0.00, 0.01, 0.02 and 0.00). Conclusion: It was found that concomitant management with vitamin D3 enhances the effectiveness of topical treatment (salicylic acid & clobetasol) as anti-psoriatic effect and reduces the time required for treatment. The signs and indicators of plaque psoriasis were controlled and the quality of life improved

Psoriasis is a chronic, incurable inflammatory skin disease characterized by immune cell infiltration, aberrant keratinocyte differentiation, and enhanced angiogenesis. Overexpression of the vascular endothelial growth factor-A (VEGF-A) gene promotes angiogenesis and is essential for endothelial cell migration, adhesion, and proliferation. Therefore, downregulating VEGF-A represents a promising therapeutic strategy for angiogenesis-related disorders. We investigated the application of Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) ribonucleoprotein complexes (sgRNA/eGFP-Cas9 RNPs) targeting VEGF-A in psoriasis. To enable efficient delivery in vitro and in vivo, we developed lipopolymeric nanoplexes (NPXs) encapsulating sgRNA/eGFP-Cas9 RNPs. These NPXs exhibited a particle size of 142.2 nm (polydispersity index: 0.144), a zeta potential of +4.27 mV, and achieved >70% transfection efficiency in HaCaT (human immortalized keratinocyte) cells. Ex vivo skin permeation studies demonstrated 66% of permeation after 24 h. The optimized NPX formulation was incorporated into a Carbopol-based gel, which displayed non-Newtonian, shear-thinning behavior with variable thixotropy and achieved 48% of skin permeation after 24 h. In vivo efficacy assessment in an imiquimod-induced psoriasis model in Swiss albino mice showed significantly improved Psoriasis Area and Severity Index (PASI) scores, reduced epidermal damage, and suppressed keratinocyte proliferation compared to naked RNPs and blank gel controls. Gene editing analysis revealed an indel frequency of 40.7% by T7 endonuclease I assay and 14% by Sanger sequencing. Enhanced cellular uptake, efficient skin permeation and retention, and improved therapeutic efficacy collectively highlight the potential of NPX-mediated CRISPR/Cas9 delivery as a noninvasive strategy for psoriasis treatment.

Psoriatic arthritis (PsA) and juvenile PsA (jPsA) are chronic inflammatory diseases with similar features that differ by age and sequence of symptom onset. PsA and psoriasis (PsO) share comparable pathology across ages, with interleukin (IL)-23 as a key mediator. Prior tothe recentUS FDA approval of guselkumabfor treatment of pediatric plaquePsO and active jPsA,no approved pediatric treatment selectively targeted IL-23 signaling. Guselkumab (a fully human, dual-acting, IL-23p19 subunit inhibitor) was shown to be safe and effective in adult PsO and PsA, with consistent clinical benefits and safety in pediatric PsO. As jPsA shares features, including clinical characteristics and pathogenesis, with PsO and PsA, findings were extrapolated to jPsA using a similar approach previously applied to support ustekinumab and golimumab use in jPsA, which served as precedents for these analyses with guselkumab. The aim of this study was to demonstrate the similarity of serum guselkumab concentrations, clinical response, and safety among children and adults with PsO and/or PsA in guselkumab randomized controlled trials. One-year data from participants receiving guselkumab at Week (W)0, W4, then every 8 weeks in VOYAGE 1/2 (adult PsO; N=1221), DISCOVER-1/-2 (adult PsA; N=375), and PROTOSTAR (pediatric PsO; N=92; n=3 with concurrent jPsA) were included. Serum guselkumab concentrations, Investigator Global Assessment of clear/minimal (IGA 0/1) and Psoriasis Area and Severity Index (PASI) 75/90/100 response rates and safety outcomes were summarized. Serum guselkumab concentrations over 1 year were similar between pediatric (max median: 3.2µg/mL) and adult PsO (3.7µg/mL), adult PsO and PsA (4.2µg/mL), and pediatric PsO and adult PsA. IGA0/1 response rates at W16 were approximately similar in guselkumab-treated participants with pediatric PsO (66%), adult PsO (84%), and adult PsA (77%). W16 PASI75/90/100 response rates were comparable across guselkumab-treated participants with pediatric PsO without jPsA (PASI75: 77%; PASI90: 56%; PASI100: 33%), pediatric PsO with jPsA (1 of 2 participants achieved all PASI improvement levels), and adult PsA (77%; 55%; 22%). Guselkumab safety outcomes were similar across ages and diseases. Comparable pharmacokinetic and clinical findings with guselkumab in children with PsO (3 with concurrent jPsA) and adults with PsO and PsA support the extrapolation of efficacy and safety data from adults to children with jPsA, supporting guselkumab use in jPsA. The clinical trials included in this analysis are registered at www. gov with the identifiers: NCT02207231 (VOYAGE 1), NCT02207244 (VOYAGE 2), NCT03162796 (DISCOVER-1), NCT03158285 (DISCOVER-2), and NCT03451851 (PROTOSTAR).

Psoriasis, a chronic inflammatory dermatological condition, exhibits heterogeneous responses to anti-TNF therapies such as etanercept (ETN), underscoring the need for predictive biomarkers. This study investigated the association of interleukin-1 beta (IL-1β) gene promoter polymorphisms (rs1143623 C/G, rs752338864 C/G, and rs1143627 C/T) with ETN efficacy in 80 Iraqi patients with moderate to severe plaque psoriasis. Patients were categorized according to treatment response: responders achieved ≥ 75% reduction in the Psoriasis Area and Severity Index (PASI), whereas non-responders demonstrated ≤ 50% reduction. Post-treatment serum IL-1β levels were significantly higher in non-responders (50.35 ± 15.81 pg/mL) compared to responders (35.38 ± 10.35 pg/mL; p = 0.001). Genotyping revealed that the rs752338864 CC genotype was exclusively present in responders (25% vs 0% in non-responders; p = 0.001) and showed a strong inverse correlation with non-responder status (ϕ = −0.342; p = 0.003), as well as a greater reduction in PASI score (p = 0.01). Logistic regression further identified serum IL-1β concentration as an independent predictor of non-response (OR = 1.11; p = 0.0115). In contrast, the other investigated SNPs (rs1143623 C/G and rs1143627 C/T) showed no significant association with treatment response. These findings suggest that the rs752338864 CC genotype may indicate a positive response, whereas increased IL-1β levels could reflect resistance to therapy. Overall, this study sheds new light on psoriasis pharmacogenetics and demonstrates the potential for incorporating genetic and biomarker assessments into individualized treatment strategies.

PurposePsoriasis with blood stasis syndrome (BSS) demonstrates aggravated skin lesions compared to psoriasis alone; however, the underlying mechanism remains unclear. This study aims to elucidate the pathological mechanisms of skin lesion exacerbation in psoriasis from the perspective of platelet activation.MethodsA psoriasis rat model was established by topical application of imiquimod (IMQ), while a psoriasis with BSS model was induced using ice–water baths and epinephrine injection. Skin lesions were assessed via hematoxylin and eosin (H&E) staining. Hemorheology was employed to evaluate BSS characteristics. Western blot (WB) was used to examine CD62P (P-selectin) and platelet-activating factor receptor (PAFR) expression to assess platelet activation. The platelet aggregation inhibitor clopidogrel was administered via oral gavage. The psoriasis area and severity index (PASI) was applied to evaluate clopidogrel’s therapeutic effect, and network pharmacology combined with quantitative reverse transcription PCR (RT–qPCR) was used to clarify its mechanism.ResultsHE staining indicated more severe skin lesions in psoriasis with BSS rats than in psoriasis rats (P<0.01). Hemorheological analysis revealed increased blood viscosity and microvascular proliferation in the psoriasis rats with BSS. WB showed significantly elevated expression of CD62P and PAFR in psoriasis with BSS rats (P<0.05). Clopidogrel reduced epidermal thickening, as assessed by the PASI score. Network pharmacology and RT–qPCR identified P2RY12 and GPIIb/IIIa as key targets through which clopidogrel ameliorates skin lesions in psoriasis with BSS.ConclusionPsoriasis with BSS rats exhibit more severe skin lesions than psoriasis rats, associated with enhanced platelet activation. Clopidogrel improved blood stasis and skin inflammation, confirming that platelet activation contributes critically to skin lesion worsening.

Background: Psoriasis is a chronic autoimmune skin disorder characterised by persistent oxidative stress and elevated serum lipid levels, which are risk factors for atherosclerosis. Carotid intima-media thickness (CIMT) is a validated measure of subclinical atherosclerosis, while chronic inflammation in psoriasis may contribute to both entheseal and vascular pathology. Hence, this study was aimed to evaluate subclinical atherosclerosis using CIMT, serum lipid levels and their correlation with ultrasonographic enthesopathy in psoriasis patients without musculoskeletal symptoms. Methods: A single-centred, comparative cross-sectional study was conducted, including 80 psoriasis patients without musculoskeletal symptoms or comorbidities and 80 age- and sex-matched healthy controls. Demographic parameters, Psoriasis Area and Severity Index (PASI), body mass index (BMI), and serum lipid profiles (total cholesterol, LDL, HDL, VLDL, triglycerides) were assessed. Ultrasonographic CIMT and entheseal sites were evaluated using OMERACT ultrasound consensus criteria. Entheseal scores were correlated with CIMT, BMI, and lipid levels, and results were compared between groups using the standard t-test. Results: Psoriasis patients (mean age: 41.56 years; mean disease duration: 5.85 years) showed significantly higher mean CIMT, LDL, VLDL, and total entheseal scores compared to controls (p&lt;0.05). Ultrasonographic entheseal inflammation scores significantly correlated with serum triglycerides, LDL, VLDL, and CIMT, while entheseal structural scores correlated with LDL, VLDL, and CIMT (p&lt;0.05). Conclusions: Subclinical atherosclerosis, serum lipid levels, and ultrasonographic entheseal abnormalities in psoriasis patients are significantly associated, reflecting a heightened inflammatory burden that links vascular and entheseal pathologies. These findings emphasise the need for integrated cardiovascular and musculoskeletal monitoring in psoriasis management.

Roflumilast cream 0.3% contains a selective, highly potent phosphodiesterase4 inhibitor approved to treat plaque psoriasis. The Psoriasis Area and Severity Index (PASI)-High Discrimination (PASI-HD) is more precise than PASI when psoriasis involves < 10% of the area of an anatomic region. Clinical trials of roflumilast utilized PASI and its modified version, PASI-HD, to assess disease improvement. The objective of this analysis was to demonstrate the effect of topical roflumilast in patients with psoriasis and to compare PASI-HD with PASI. DERMIS-1 and DERMIS-2 were phaseIII, 8-week, randomized, vehicle-controlled trials of once-daily roflumilast cream 0.3% in patients aged ≥ 2years with psoriasis involving 2-20% body surface area. PASI and PASI-HD were clinical endpoint measures. At week8, statistically significantly more roflumilast- than vehicle-treated patients achieved ≥ 75% reduction in PASI (40.3% vs 6.5%; P < 0.0001) and PASI-HD (59.9% vs 17.9%; P < 0.0001). Evaluations using PASI-HD resulted in larger effect sizes compared with PASI at higher levels of response. Roflumilast-treated patients experienced greater improvements in disease severity than vehicle-treated patients. The PASI-HD can more accurately assess disease changes compared with PASI. ClinicalTrials.gov Identifiers: DERMIS-1, NCT04211363; DERMIS-2, NCT04211389.

Background Psoriasis is a chronic systemic inflammatory disease mediated by the immune system. Interleukin-23 (IL-23) plays a key role in its pathogenesis by amplifying inflammation, triggering atherogenic dyslipidemia and insulin resistance, and thereby increasing cardiovascular and cerebrovascular risk. This study aimed to evaluate the effect of the IL-23 inhibitors risankizumab and guselkumab, used in psoriasis treatment, on cardiovascular and cerebrovascular risk through the plasma atherogenic index (PAI) and triglyceride-glucose (TyG) index. Methods This retrospective study included 110 patients diagnosed with psoriasis and treated with risankizumab (n = 61) or guselkumab (n = 49). Psoriasis Area and Severity Index (PASI) scores, triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), very low-density lipoprotein cholesterol (VLDL-C) levels and fasting blood glucose (FBG) values at baseline and at 6 months of treatment were obtained from patient records. The plasma atherogenic index (PAI) was calculated as log₁。(TG/HDL-C), and the triglyceride-glucose (TyG) index as log₁。(TG × FBG / 2). Results In both IL-23 inhibitor groups included in the study, PASI scores, PAI, and TyG index values showed a significant decrease from baseline at the 6th month of treatment (p < 0.05). However, there was no significant difference in the reduction of index levels between the groups (p > 0.05). Conclusion IL-23 inhibitors can reduce atherogenic dyslipidemia and insulin resistance alongside dermatological improvement in the treatment of psoriasis. This suggests a potential role for these agents in reducing the risk of cardiovascular and cerebrovascular disease. However, large-scale, long-term studies are needed to confirm these beneficial effects.

Hypothalamic pituitary adrenal axis hormone changes during IL-17A inhibition with secukinumab in patients with psoriasis.

BackgroundAlthough biologic and systemic therapies have advanced psoriasis management, real-world evidence guiding individualized treatment remains limited. In particular, the influence of body size and metabolic parameters on disease severity and treatment response is underexplored.ObjectiveTo investigate the associations of body mass index (BMI), basal metabolic rate (BMR), body surface area (BSA), and body weight with baseline psoriasis severity and therapeutic response across different treatment modalities.MethodsThis multicenter, prospective study included 1955 patients from the Shanghai Psoriasis Effectiveness Evaluation CoHort (SPEECH) and 1663 patients for longitudinal follow-up. Multivariable regression models were used to examine the associations between body size/metabolic parameters and the baseline psoriasis area and severity index (PASI) scores, as well as PASI-based treatment responses at Week 12 and Week 20. Stratified analyses by treatment type and receiver operating characteristic curve analysis were conducted to assess predictive performance.ResultsAll four parameters were positively associated with baseline PASI scores (FDR-adjusted P < 0.05). Prospectively, elevated BMI, BMR, BSA, and body weight were significantly associated with reduced likelihood of achieving PASI 75/90/100, and lower percentage reduction in PASI score at both time points. These associations were particularly pronounced in patients receiving biologic therapies. In the ustekinumab subgroup, body composition showed enhanced predictive accuracy for high-level PASI responses.ConclusionElevated BMI, BSA, body weight, and BMR are associated with more severe psoriasis and diminished treatment efficacy, especially those treated with biologics. These findings underscore the need for personalized dosing strategies in biologic therapy, especially for fixed-dose agents like ustekinumab.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12967-025-07130-w.

BackgroundPsoriasis (PsO) is a prevalent chronic disease affecting millions, with biologic therapies like secukinumab showing efficacy. With the extensive and prolonged use of secukinumab, identifying strategies for successful dose tapering has emerged as a recent challenge.ObjectiveThis retrospective study aims to identify predictors of successful secukinumab dose tapering in patients with moderate-to-severe plaque psoriasis.MethodsThis retrospective study included patients who received secukinumab 300 mg weekly for 5 weeks, then every 4 weeks, achieving and maintaining Psoriasis Area and Severity Index (PASI) 90 for ≥6 months. Statistical analyses included the Mann–Whitney U-test, Friedman M test, and logistic regression (P<0.05).ResultsAmong the 75 secukinumab-treated patients, 40 (53.33%) successfully tapered their dosage. BMI, dose tapering timing, and pre-tapering treatment duration were significant predictors of tapering success. Seasonal effects were observed, with autumn and winter attempts having an increased risk of failure. PASI 75 and PASI 90 rates dropped from week 6 to 12, with no serious adverse events.ConclusionLower BMI, dose tapering initiation in spring and summer, and rapid PASI 90 achievements are associated with successful secukinumab dose tapering. These findings suggest that, under appropriate clinical conditions, dose tapering may be a feasible strategy to maintain disease control while potentially reducing treatment-related costs and minimizing the risk of adverse effects.

Secondary failure to biologic disease-modifying antirheumatic drugs (bDMARDs) is challenging and contributes to the complexity of managing psoriatic arthritis (PsA). We aimed to define the frequency and incidence of this phenomenon in PsA and identify the risk factors for its occurrence. We retrieved data on patients with PsA from our single-center, specialized-care, prospective observational cohort who initiated and remained on bDMARDs for ≥ 1 year after clinic enrollment between 2000 and 2023. We defined response to therapy at the 1-year visit (baseline) as achievement of ≥ 40% reduction in the swollen joint count (SJC) and either ≥ 50% reduction in Psoriasis Area and Severity Index (PASI) or PASI ≤ 2. We defined secondary failure as the inability to maintain response criteria or as the clinician's judgment of loss of effectiveness. To examine factors associated with secondary failure, we fitted Cox regression models. Of 482 patients included in the study, 264 (54.8%) were responders at 1 year. Of these, 94 (35.6%) developed secondary failure at a median of 1.6 (IQR 0.7-3.8) years from response. In the multivariable model, higher SJC (hazard ratio [HR] 1.39, 95% CI 1.05-1.84) and PASI (HR 1.14, 95% CI 1.01-1.29) at baseline were associated with secondary failure. Tumor necrosis factor inhibitors (TNFi) vs other bDMARD use (HR 0.39, 95% CI 0.18-0.88), initiation as first-line bDMARD (HR 0.48, 95% CI 0.25-0.91), and treatment initiation during more recent calendar years (HR 0.34, 95% CI 0.12-0.98) were associated with less secondary failure. Secondary failure to bDMARD is common in PsA and may be influenced by both disease- and therapy-related factors.

BackgroundPsoriasis is a chronic immune-mediated inflammatory disease. Systemic therapy is usually applicable to patients who have failed topical treatment or phototherapy, but the value of early systemic therapy remains unclear.PurposeThis study aimed to evaluate the impact of disease duration on the clinical efficacy and patients reported outcomes in moderate to severe psoriasis patients treated with systemic agents.MethodsOur research was based on the SPEECH, an observational, prospective, multicenter registry. Adult patients with moderate to severe psoriasis receiving systemic therapy (including biologics, methotrexate or acitretin) were divided into groups based on disease duration: <2 years, 2~10 years, and ≥10 years. The clinical efficacy was assessed using PASI (Psoriasis Area and Severity Index), BSA (Body Surface Area), PGA (Physician Global Assessment). The Dermatology Life Quality Index (DLQI), PtGA (Patient Global Assessment) and the Hospital Anxiety and Depression Scale (HADS) were used to assess the patients reported outcomes. The treatment outcomes were analyzed at 3 months and 6 months. Using multiple logistic regression to analyze the differences between patients with different disease duration, and conducting subgroup analysis and sensitivity analysis to test the robustness of the research results.ResultsA total of 1908 patients who met the criteria were included in the analysis. After 3 months of treatment, the PASI75 response rates for the three groups of patients (<2 years, 2–10 years, and ≥10 years) were 55%, 55% and 60%, respectively all p value >0.05. No significant differences were observed among the three groups in the rates of achieving BSA <1/3, PGA 0/1, DLQI 0/1, PtGA 0/1, HADS-A = 0, and HADS-D = 0. Notably, these outcomes still showed no significant differences at 6 months. Subgroup and sensitivity analyses also yielded consistent results.ConclusionDisease duration does not significantly affect clinical efficacy or patients reported outcomes in patients with moderate-to-severe psoriasis receiving systemic therapy. These results indicate that early systemic therapy does not improve treatment outcomes in real clinical settings, thereby supporting the continued efficacy of step-up treatment strategy and providing novel insights into clinical practice management.

Background/Objectives: The advent of biologics targeting key inflammatory pathways has significantly advanced psoriasis treatment. Among them, the Interleukin-23 inhibitors Guselkumab and Risankizumab have demonstrated high efficacy and rapid clinical response in both clinical trials and real-world studies. However, up to 30% of patients fail to respond. This study aimed to identify pharmacogenetic markers associated with treatment response using a genome-wide association study (GWAS) and protein network-based approach. Methods: Fifty-three patients of Greek origin with moderate-to-severe plaque psoriasis were treated with Guselkumab or Risankizumab. Based on Psoriasis Area and Severity Index (PASI) improvement at 3 and 6 months, patients were categorized as responders or non-responders. Approximately 730,000 single-nucleotide polymorphisms (SNPs) were genotyped. After filtering, a GWAS was performed to identify variants associated with treatment response. Additionally, protein–protein interaction (PPI) network analysis was applied to the two Interleukin-23 subunits and SNPs within or near genes encoding Interleukin-23-interacting proteins to test for their association. Results: The GWAS identified two novel variants, rs73641950 and rs6627462, significantly associated with treatment response, with both surpassing the genome-wide significance threshold after Bonferroni correction. The PPI-based approach revealed rs13086445, located downstream of the Interleukin-12 subunit alpha (IL12A) gene, as another associated variant. All three SNPs lie in genomic regions with potential regulatory roles. Conclusions: This study identifies three novel genetic variants associated with response to Interleukin-23 inhibitors in psoriasis. These findings provide promising pharmacogenetic markers which, upon validation in larger, independent cohorts, will enable the translation of a patient’s genotype into a response phenotype, thereby guiding clinical decisions and improving drug effectiveness.

Background/Objectives: Psoriasis is currently treated with biologics targeting the IL-17A signaling, which plays a major role in immune response and keratinocyte hyperproliferation. These include inhibitors of IL-17A and/or its heterodimer with IL-17F (Secukinumab, Ixekinumab and Bimekizumab) and the receptor IL17-RA (Brodalumab). Although these drugs are safe and highly effective, there is significant variability in response among patients. This can be partly attributed to the patients’ genetic background, thus pointing to the need to identify pharmacogenetic markers for treatment response. Methods: The study involved 88 Greek patients who were treated with inhibitors of the IL-17A signaling for at least 6 months. Patients were classified as responders and non-responders according to the change in Psoriasis Area Severity Index. A total of 730,000 variants were genotyped and analyzed for association with the 3-month and 6-month responses to treatment. Results: The analysis identified 21 variants which were associated with the response, showing statistical significance after Bonferroni correction. These include variants located in protein coding genes (TP63, NRG1, SCN8A, TAF9, TMEM9, SMIM36, SYT14, BPIFC, SEZ6L2, PCARE), as well as intergenic and long non-coding RNA intronic variants. The functional significance of the variants was assessed using in silico analysis and for several variants, a link with immune processes was proposed. Notably, rs11649499 status, which was associated with complete clinical remission at 3 months, may influence key lipid mediators involved in psoriasis. Conclusions: This GWAS identified novel variants that could be utilized upon validation in larger populations as predictive markers regarding patient response to drugs targeting the IL-17A pathway.

Background and Objectives: This study is aimed at evaluating periodontal health in patients with psoriasis and investigating its impact on dermatology-specific and oral health-related quality of life. Materials and Methods: A total of 226 individuals were enrolled, including 113 patients with clinically diagnosed psoriasis and 113 age- and gender-matched healthy controls. The periodontal parameters recorded included plaque index (PI), gingival index (GI), probing depth (PD), and clinical attachment loss (CAL). Oral health-related quality of life was assessed using the Oral Health Impact Profile-14 (OHIP-14), while dermatology-specific quality of life was evaluated with the Psoriasis Quality of Life Questionnaire (PQLQ). Psoriasis severity was measured by the Psoriasis Area and Severity Index (PASI). Results: Patients with psoriasis demonstrated significantly poorer periodontal parameters compared to controls, with higher PI (p = 0.006), PD (p = 0.001), and CAL (p = 0.041), as well as a lower number of teeth (p = 0.027). No significant differences in GI were observed (p = 0.331). Subdomain analysis of OHIP-14 indicated significantly greater functional limitation in the psoriasis group (p = 0.001), although no differences were detected in other domains. Positive and significant correlations were found among all the OHIP-14 subscales in both groups, and PQLQ scores were strongly correlated with OHIP-14 outcomes in the psoriasis group (p < 0.05). PASI scores tended to be higher among patients with periodontitis than those with gingivitis or periodontal health, but this difference did not reach statistical significance (p = 0.257). Conclusions: Psoriasis patients exhibited poorer periodontal status and reduced oral health-related quality of life compared to healthy individuals. However, differences in oral hygiene habits may also have contributed to these findings. Our findings suggest an association between psoriasis and impaired periodontal health, but due to the cross-sectional design, a causal relationship cannot be established.

ABSTRACTBackgroundPsoriasis is a chronic inflammatory skin condition affecting millions globally, traditionally assessed via the Psoriasis Area and Severity Index (PASI). Despite its widespread use, PASI suffers from subjectivity, limited sensitivity for small lesions, and high interobserver variability. Recent advances in artificial intelligence offer a promising route to overcome these limitations.ObjectivesThis study aimed to develop and validate the Automatic Psoriasis Area and Severity Index (APASI), an AI‐driven system for rapid, objective, and standardised assessment of psoriasis severity.MethodsWe compiled the Legit.Health‐PsO‐PASI dataset, consisting of 2857 images spanning various disease severities and annotated by three expert dermatologists. Two deep learning modules were developed: one for lesion segmentation and another for visual sign intensity classification (erythema, induration and desquamation). Multiple encoder architectures, including ResNet, SE_ResNeXt, Xception, Inceptionv4, EfficientNet, and SegFormer, were evaluated using a five‐fold cross‐validation approach. Performance metrics included accuracy, root mean square error, intersection over union, confusion matrices and Cohen's kappa for assessing interobserver variability.ResultsThe best‐performing model, MiT_b2, achieved human‐comparable performance, with accuracies of 60.6% for erythema, 54.3% for induration, and 61.8% for desquamation. For lesion segmentation, the Xception model outperformed expert dermatologists, achieving an intersection over union of 0.752.ConclusionsAPASI provides a robust AI‐driven framework for psoriasis severity assessment, delivering rapid, objective, and precise evaluations. Its integration into clinical and research workflows could enhance disease monitoring, improve treatment assessment and reduce evaluation costs.

Psoriasis is a chronic immune-mediated inflammatory skin disorder characterized by keratinocyte hyperproliferation and immune cell infiltration. Low molecular weight sulfated galactan (LSG), derived from the red seaweed Gracilaria fisheri, has immunomodulatory potential relevant to psoriasis pathogenesis. The present study investigated the therapeutic potential of LSG using an imiquimod (IMQ)-induced murine model of psoriasis. BALB/c mice received intraperitoneal administration of LSG once daily, 2 h prior to IMQ application, for 7 consecutive days. Clinical severity was assessed using the Psoriasis Area and Severity Index (PASI). Histopathological and immunohistochemical analyses were performed to evaluate epidermal architecture, vascular change and immune cell infiltration. Expression of keratinocyte proliferation and differentiation markers, proinflammatory cytokines and JAK/STAT pathway components was analyzed using reverse transcription-quantitative PCR, ELISA and western blotting. Systemic inflammation was assessed by spleen and lymph node size. LSG significantly decreased PASI scores, neovascularization, epidermal thickness and dermal inflammation. LSG downregulated keratinocyte proliferation and differentiation markers (Ki67, keratin 6, 16 and 17, involucrin) and decreased proinflammatory cytokine expression (TNF-α, IL-1β, IL-17A, IL-23, IL-6), accompanied by decreased CD4+ T and mast cell infiltration. LSG downregulated JAK2/STAT2/STAT3 signaling and downstream genes (BCL2, CCND1). Furthermore, LSG alleviated systemic inflammation without inducing hepatic or renal toxicity. These findings indicated that LSG effectively ameliorates IMQ-induced psoriatic inflammation via coordinated reduction of keratinocyte hyperproliferation, cytokine production and immune cell activity. LSG represents a promising marine-derived therapeutic candidate for psoriasis management.

Psoriatic arthritis (PsA) is a progressive, multidomain and interleukin-17 (IL-17)-linked disease that results in substantial quality-of-life deficits. Thereby, we conducted a phase 2 randomized, double-blind, placebo (PBO)-controlled trial of sonelokimab (SLK), a nanobody that binds with a similarly high affinity to IL-17A and IL-17F, inhibiting all dimers. Overall, 207 patients with active PsA were randomized to SLK 120-mg or 60-mg every 4 weeks (Q4W; both with induction (WI)), or to 60-mg Q4W with no induction, PBO or adalimumab (reference arm). The primary endpoint of American College of Rheumatology (ACR) 50 at week 12 was met for SLK 60-mg and 120-mg WI (60-mg WI = 46.3% (19/41; odds ratio (OR) = 3.6; 95% confidence interval (CI) = 1.3-9.9; P < 0.05); 120-mg WI = 46.5% (20/43; OR = 4.0; 95% CI = 1.4-11.3; P < 0.01) versus PBO = 20.0% (8/40)). SLK resulted in significant benefits across the key secondary endpoints of ACR20 (60-mg WI = 78.0% (32/41; P < 0.001) and 120-mg WI = 72.1% (31/43; P = 0.002) versus PBO = 37.5% (15/40)) and Psoriasis Area and Severity Index (PASI) 90 at week 12 (60-mg WI = 76.9% (20/26; P < 0.001) and 120-mg WI = 59.3% (16/27; P = 0.003) versus PBO = 15.4% (4/26)). Robust responses were observed among patients randomized to SLK at week 24 for the high-threshold composite endpoints of ACR70 + PASI 100 (exploratory) and minimal disease activity (secondary), achieved by up to 48% (13/27; 120-mg WI) and 61% (25/41; 60-mg WI), respectively. SLK was well-tolerated; the most common treatment-emergent adverse events were nasopharyngitis (60 mg = 6.1%; 120 mg = 5.2%), upper respiratory tract infection (60 mg = 6.1%; 120 mg = 4.1%), injection-site erythema (60 mg = 3.7%; 120 mg = 3.1%) and headache (60 mg = 2.4%; 120 mg = 4.1%). Four cases of mild to moderate oral candidiasis occurred (60 mg = 2.4%; 120 mg = 2.1%). Overall, SLK delivered substantial improvements in the signs and symptoms of PsA across various outcomes and domains. ClinicalTrials.gov registration: NCT05640245 .