Psoriasis Area And Severity Index Score Research Articles

Real-World Long-Term Effectiveness of Risankizumab Among Patients with Moderate-to-Severe Psoriasis: Analysis from an International Medical Chart Review (RAPID) Study.

Real-world data on the efficacy of risankizumab (RZB) in clinical moderate-to-severe plaque psoriasis (PsO) are limited. The RAPID study assessed real-world clinical and patient-reported outcomes in RZB-treated PsO patients using data collected from dermatologists in Canada, the Czech Republic, Germany, Japan, and Poland. This ongoing, retrospective chart review collected data from medical records of RZB-treated adults with moderate-to-severe PsO (09/2022-06/2023). Eligible patients received RZB, had ≥ 12months of medical records after RZB initiation (index date), and had Psoriasis Area and Severity Index (PASI), Investigator Global Assessment (IGA), or static Physician's Global Assessment (sPGA) scores ≥ 3months before and up to 18months after the index date. The proportion of patients achieving a clear/almost clear PsO (IGA/sPGA = 0/1), PASI ≤ 1, Dermatology Life Quality Index (DLQI) = 0/1, and a 90%/100% improvement from baseline in PASI as well as the mean changes in PASI, DLQI, itch, and skin pain scores at 12 and 18 months were reported for patients with non-missing assessments at baseline and 12months. Most patients (66.4%) were male, 74.0% were biologic naïve, and 73.0% had scalp PsO. Mean baseline IGA/sPGA was 3.7 ± 0.5, with a mean PASI of 23.3 ± 11.8. After 12months, 86.1% of patients reported IGA/sPGA ≤ 1, and 75.7% achieved PASI90; these further increased to 91.1% and 80.5% at 18months. DLQI, itch, and skin pain scores improved over time. These data demonstrated the durable, real-world effectiveness of RZB in patients with moderate-to-severe PsO through continued improvement in disease and symptom severity over 18months, with most of the patients reporting clear/almost clear skin.

Identification of the immune repertoire of γδ T-cell receptors in psoriasis.

The γδ Tcells are a subpopulation of Tcells that are abundantly found in the skin and mucous membranes. Their reactivity to self-antigens and ability to secrete various cytokines make them a key component in psoriasis development. Although the correlation between the immune repertoire (IR) of γδ T-cell receptors and the occurrence and severity of psoriasis remains incompletely explored, high-throughput sequencing of γδ Tcells has led to a deeper understanding of IR in psoriasis. This study investigated the differences between γδ Tcells in patients with psoriasis and healthy controls. The γδ Tcells were identified via immunofluorescence staining and a correlation analysis was performed according to the psoriasis area and severity index (PASI) scores. The IR sequencing method was used to detect IR in the γδ T-cell receptors. The findings demonstrated more skin γδ Tcells in patients with psoriasis, which were positively correlated with the PASI score. There were subtle differences in most variable (V), diversity (D) and joining (J) gene segments and VJ/VDJ combination segments between patients with psoriasis and healthy controls. However, a higher diversity of complementarity-determining region 3 (CDR3) was observed in patients with psoriasis. In summary, the IR of skin γδ Tcells was significantly altered in patients with psoriasis, and the diversity in the cell's CDR3 population is a promising biomarker for assessment of psoriasis severity.

Impact of residual skin lesions and previous biologic treatment failure on patient-reported outcomes in patients with psoriasis receiving biologic treatment.

Recent advances in biologic treatments have made clear skin a realistic treatment goal for psoriasis. However, clear skin may not uniformly translate to an absence of impact on patients' quality of life. This retrospective observational study aimed to elucidate the factors influencing patient-reported outcomes in patients with psoriasis who have demonstrated successful clinician-reported outcomes on using biologics. A total of 96 patients who have achieved a ≥75% improvement in Psoriasis Area and Severity Index (PASI) scores with ≥6 months of biologic treatment were included. Their median PASI score was 0.4, with 37.5% having achieved PASI 100 (clear skin). Furthermore, 47.9% reported no impact of psoriasis on their quality of life (Dermatology Life Quality Index [DLQI] score 0 or 1), while 52.1% reported a negative impact (DLQI score ≥2). Notably, 28.1% of the participants had a history of biologic treatment failure, defined as the inability to achieve or sustain a 75% PASI improvement with the previously used biologic agent. Multivariable logistic regression analysis revealed a positive association between achieving PASI 100 and reporting no impact of psoriasis on quality of life (adjusted odds ratio [aOR] 3.88, 95% confidence interval [CI] 1.49-10.91, P = 0.007). Conversely, prior biologic treatment failure was negatively associated with reporting no impact of psoriasis on quality of life (aOR 0.13, 95% CI 0.02-0.65, P = 0.023). Furthermore, among patients with clear skin, those with experience of previous biologic treatment failure reported significantly lower quality of life than those without such experience (P = 0.033). In conclusion, minimal residual skin lesions and prior biologic treatment failure were associated with poorer patient-reported outcomes in patients with psoriasis. Opting for a biologic agent with the highest predicted efficacy, rather than pursuing a "step-up" approach with a higher possibility of treatment failure, may be a more suitable strategy in the biologic treatment of psoriasis.

Effectiveness, safety and impact of guselkumab on sexuality and perceived stigmatization in patients with psoriasis in routine clinical practice: Week 28 results from the prospective German multicentre G-EPOSS study.

G-EPOSS is a prospective, non-interventional, German multicentre study of patients with moderate-to-severe plaque psoriasis receiving guselkumab, a therapeutic monoclonal antibody targeting interleukin-23, in a real-world setting. The objective of the study was to evaluate the effectiveness and safety of guselkumab, including its impact on skin, health-related quality of life (HRQoL), sexuality, and perceived stigmatization. Patients (≥18 years old) received guselkumab per routine clinical practice. The primary endpoint was the proportion of patients achieving absolute Psoriasis Area and Severity Index (PASI) ≤ 3 at Week (W)28. Secondary endpoint assessments over 28 weeks included the Nail Psoriasis Severity Index (NAPSI), anogenital Physician's Global Assessment (aPGA), and Dermatology Life Quality Index (DLQI). Sexuality and perceived stigmatization were assessed by patients using the Relationship and Sexuality Scale (RSS) and Perceived Stigmatization Questionnaire (PSQ), respectively. Overall, 293 patients were included in the evaluable set population. Mean age and disease duration were 45.6 and 17.6 years, respectively. At baseline, mean PASI, aPGA and DLQI scores were 15.3, 2.7 and 11.3, respectively. In total, 25.9% of patients had received a prior biologic. Overall, 83.0% of patients achieved PASI ≤ 3, and 56.2%/35.1% achieved PASI ≤ 1/PASI = 0, respectively, at W28. Among those with NAPSI ≥ 1 and aPGA ≥ 1 at baseline, NAPSI = 0 and aPGA = 0 were achieved by 39.2% and 61.1% of patients, respectively, and 61.4% of patients achieved DLQI 0-1 at W28. Improvements were observed over 28 weeks across individual items of the DLQI, RSS and PSQ, indicating improved HRQoL and sex life, and decreased perceived stigmatization. Based on DLQI Question (Q)9, 53.6% of patients experienced sexual difficulties at baseline, which decreased to 12.1% at W28. DLQI Q9 responses were consistent with RSS item responses, highlighting DLQI Q9 as a sentinel for sexual impairment. Guselkumab improved overall skin symptoms and HRQoL in patients with psoriasis and decreased sexual impairment and perceived stigmatization. No new safety signals were observed. CNTO1959PSO4008.

Effectiveness of risankizumab for the treatment of psoriatic arthritis: a multicenter, real-world study.

IL-23 inhibitors were recently approved for the treatment of skin psoriasis and psoriatic arthritis (PsA). Risankizumab, a humanized monoclonal antibody that specifically binds the p19 subunit of IL-23, has proven effective on PsA in two randomized controlled trials. To date, only a few real-world data are available on this topic. Our study aimed to prospectively evaluate the effectiveness of risankizumab in patients with PsA in a real-world setting. For this purpose, both rheumatologic and dermatologic assessments were performed at baseline and after 28-40 weeks of continuous risankizumab administration. Moreover, joint and entheses ultrasound assessment was performed at the mentioned time points. The rheumatologic assessment was carried out by means of the following scores: (i) clinical Disease Activity Index for Psoriatic Arthritis (cDAPSA); (ii) Leeds Enthesitis Index (LEI); (iii) Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and (iii) Bath Ankylosing Spondylitis Functional Index (BASFI). The degree of skin involvement was measured by both the Psoriasis Area and Severity Index (PASI) and Physician Global Assessment (PGA). Quality of life was assessed by the Health Assessment Questionnaire (HAQ) and Dermatology Life Quality Index (DLQI). Ultrasound assessment of joints and entheses was performed on the basis of the EULAR-OMERACT score. After treatment, cDAPSA decreased from a mean value of 12.9 ± 7.6 to 7.0 ± 6.1 (P < 0.001), and the median PD score significantly decreased from baseline (3; range 1-8) to TP1 (1; range 0-7) (P < 0.001). PASI score also decreased from 8.4 ± 4.9 to 0.3 ± 0.5 (P < 0.001), and PGA from 3.1 ± 1.0 to 0.4 ± 0.5 (P < 0.001). We can conclude that risankizumab led to substantial improvement in both skin and joint involvement.

Non-alcoholic Fatty Liver Disease Among Iraqi Patients With Psoriasis: A Case-Control Study.

Non-alcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease worldwide. Several studies have shown that patients with psoriasis have a higher risk of developing NAFLD. Obesity, metabolic syndrome, and cytokine-mediated inflammation might be the link between psoriasis and NAFLD. This study aims to investigate the prevalence of NAFLD among psoriatic Iraqi patients and examine the relationship with disease severity using the Psoriasis Area and Severity Index (PASI) score and the correlation with different clinical and laboratory parameters. A case-control study on 130 psoriatic patients and 130 age-, sex-, and BMI-matched healthy controls was conducted at the Department of Dermatology in Basra Teaching Hospital from November 2022 to October 2023. All demographic and clinical data were collected using a pre-designed questionnaire, and NAFLD was diagnosed through a FibroScan examination performed on each participant. The severity of psoriasis was determined using the PASI score. Fasting glucose, liver enzymes, and lipid profile levels were investigated, and metabolic syndrome was identified. The prevalence of NAFLD was significantly higher in our psoriatic patients than in the control group (66.2% vs. 42.3%, OR=2.6, P<0.01). Psoriatic patients were found to have more severe NAFLD than the controls, as evidenced by their steatosis and fibrosis staging (P<0.01). In patients with psoriasis, NAFLD was associated with a higher prevalence of diabetes (17.4%) and metabolic syndrome (55.8%). Furthermore, psoriatic patients with NAFLD had significantly higher values of BMI, waist circumference, PASI score, as well as serum alanine transaminase (ALT), triglyceride, cholesterol, low-density lipoprotein (LDL), and fasting glucose levels.The study also found a significant positive correlation between the psoriasis severity based on PASI and the steatosis score. Metabolic syndrome, PASI, BMI, serum triglycerides, LDL, and age are the independent predictors of NAFLD. NAFLD is highly prevalent among psoriatic patients affecting more than half of them and closely associated with metabolic syndrome and severity of psoriasis. Routine screening for NAFLD may be necessary in psoriatic patients particularly when considering the use of hepatotoxic drug therapy.

Image-based remote evaluation of PASI scores with psoriasis by the YOLO-v4 algorithm.

As a chronic relapsing disease, psoriasis is characterized by widespread skin lesions. The Psoriasis Area and Severity Index (PASI) is the most frequently utilized tool for evaluating the severity of psoriasis in clinical practice. Nevertheless, long-term monitoring and precise evaluation pose difficulties for dermatologists and patients, which is time-consuming, subjective and prone to evaluation bias. To develop a deep learning system with high accuracy and speed to assist PASI evaluation, we collected 2657 high-quality images from 1486 psoriasis patients, and images were segmented and annotated. Then, we utilized the YOLO-v4 algorithm to establish the model via four modules, we also conducted a human-computer comparison through quadratic weighted Kappa (QWK) coefficients and intra-class correlation coefficients (ICC). The YOLO-v4 algorithm was selected for model training and optimization compared with the YOLOv3, RetinaNet, EfficientDet and Faster_rcnn. The model evaluation results of mean average precision (mAP) for various lesion features were as follows: erythema, mAP = 0.903; scale, mAP = 0.908; and induration, mAP = 0.882. In addition, the results of human-computer comparison also showed a median consistency for the skin lesion severity and an excellent consistency for the area and PASI score. Finally, an intelligent PASI app was established for remote disease assessment and course management, with a pleasurable agreement with dermatologists. Taken together, we proposed an intelligent PASI app based on the image YOLO-v4 algorithm that can assist dermatologists in long-term and objective PASI scoring, shedding light on similar clinical assessments that can be assisted by computers in a time-saving and objective manner.

Structural and functional imaging of psoriasis for severity assessment and quantitative monitoring of treatment response using high-resolution optoacoustic imaging

Psoriasis is a chronic inflammatory skin disease, characterized by thick scaly plaques. It imposes a notable disease burden with varying levels of severity affecting the quality of life significantly. Current disease severity assessment relies on semi-objective visual inspection based on the Psoriasis Area and Severity index (PASI) score that might not be sensitive to sub-clinical changes. Histology of psoriasis skin lesions necessitate invasive skin biopsies. This indicates an unmet need for a non-invasive, objective and quantitative approach to assess disease severity serially. Herein, we employ multispectral Raster-Scanning Optoacoustic Mesoscopy (ms-RSOM) derived structural and microvascular functional imaging metrics to examine the lesional and non-lesional skin in psoriasis subjects across different severities and also evaluate the treatment outcome in a subject with topical steroids and biologics, such as adalimumab. ms-RSOM derived structural metrics like epidermal thickness and microvascular functional information such as oxygen saturation (sO2) and total blood volume (TBV) are evaluated by spectrally resolving the endogenous chromophores like melanin, oxy-, and deoxy-hemoglobin. Initial findings reveal an elevated sO2 and TBV with severity in lesional and non-lesional psoriasis skin, thus representing increasing inflammation. An increase in epidermal thickness is also noted with the degree of severity, corresponding to the inflammation and increased abnormal cell growth. As a marker to evaluate the treatment response, we observed a decrease in epidermal thickness, sO2, and TBV in a psoriasis patient post-treatment, which is consistent with the decrease in the PASI score from 4.1 to 1.9. We envision that ms-RSOM has a huge potential to be translated into routine clinical setting for the diagnosis of severity and assessment of treatment monitoring in psoriasis subjects.

Polymorphisms in the CD6-ALCAM axis may modulate psoriasis risk and outcomes

The fact that CD6, along with its ligand – ALCAM, plays a role in regulating T cell activation makes the genes encoding these molecules promising candidates for research in T cell-mediated diseases such as psoriasis vulgaris (PsV). Our study aimed to determine whether CD6 (rs17824933C>G, rs11230563C>T and rs12360861G>A) and ALCAM (rs6437585C>T, rs11559013G>A) polymorphisms may affect psoriasis susceptibility and severity (assessed by Psoriasis Area and Severity Index (PASI)). Moreover, the presence of HLA-C*06:02, the strongest psoriasis risk factor in the Caucasian population, was also investigated. 273 patients diagnosed with psoriasis vulgaris and 256 blood donors with no history of PsV or other dermatoses were included in this study. Genotyping of the investigated polymorphisms was carried out using the allelic discrimination method with the application of TaqMan SNP Genotyping Assays. We observed the association of rs17824933G allele with a higher psoriasis risk in HLA-C*06:02(+) individuals (CG + GG vs CC, OR = 1.87, CI95% = 1.03; 3.37, p = 0.0350). Furthermore, we found a difference in average PASI score among groups of patients divided according to the number of CD6 and ALCAM polymorphic sites with minor alleles (F2,173 = 6.159, p = 0.0026). Collectively, our findings suggest that polymorphisms of CD6-ALCAM axis genes may modulate psoriasis risk and outcomes.

Geniposide alleviates imiquimod-induced psoriasis-like skin lesions in mice via inhibition of angiogenesis

In this study, we aimed to evaluate the protective effect of geniposide (GEN) on imiquimod (IMQ)-induced psoriasis-like skin lesions in mice. Firstly, visual changes of psoriatic skin lesions were observed and the severity was recorded using psoriasis area and severity index (PASI) score. Histological changes were assessed by HE staining for epidermal thickness and Masson’s staining for collagen fibers. Then, photographs of microvascular inside the skin were taken for macroscopic observation, and microscopic changes associated with angiogenesis were evaluated. Furthermore, expression of angiogenic factors were analyzed by ELISA, immunohistochemistry and immunofluorescence, separately. Lastly, the expression of VEGFR signaling-related proteins was detected by WB. Compared with control, IMQ drove a significant increment of epidermal thicknesses with higher PASI scores and more dermal collagen deposition. IMQ treatment led to abnormal keratinocyte proliferation, increased microvascular inside skin, growing production of angiogenesis-related factors, up-regulated expression of VEGFR1 and VEGFR2, and enhanced phosphorylation of p38. However, GEN significantly ameliorated the psoriatic skin lesions, the epidermal thickness, the formation of collagen fibers, and abnormal keratinocyte proliferation. Importantly, GEN inhibited angiogenesis, the production of angiogenic factors (VEGF-A, Ang-2, TNF-α, and IL-17A), and the proliferation of vascular endothelial cells. Simultaneously, GEN curbed the expression of VEGFR1, VEGFR2, p38, and P-p38 proteins involved in VEGFR signaling. Of note, the suppressive effect of GEN was reversed in the HUVECs with over-expressed VEGFR1 or VEGFR2 related to the cells without transfection. These findings suggest that VEGFR1 and VEGFR2 participate in the anti-angiogenesis of GEN in IMQ-induced psoriasis-like skin lesions in mice.

Effectiveness of Ixekizumab in Chinese Patients with Moderate-Severe Plaque Psoriasis with Special Area Involvement: Subanalysis of a Prospective, Multicenter, Observational Real-World Study.

Ixekizumab, a monoclonal antibody against interleukin-17A, demonstrated effectiveness in the treatment of psoriasis in a Chinese real-world study that was consistent with previous randomized controlled trials. Here, we report further analyses from this study to explore the effectiveness of ixekizumab for treating patients with psoriasis and the involvement of special body areas (scalp, nail, joint, palmoplantar, or genital areas). A multicenter, prospective, observational, single-arm, post-marketing surveillance study was conducted in patients aged ≥ 18years with moderate-to-severe plaque psoriasis and prescribed with ixekizumab in 26 Chinese hospitals. Psoriasis Area and Severity Index (PASI) and Dermatology Life Quality Index (DLQI) scores were compared between patients with versus without psoriasis in special body areas in the overall study population and across subgroups by body area. In total, 612 patients were included. At baseline, most patients (93.6%) had psoriasis involvement in at least one special body area. Overall, patients with psoriasis in special body areas reported a worse quality of life (QoL) than those without. Patients with versus without psoriasis in special body areas achieved a comparable mean reduction from baseline in PASI score (10.9 vs. 9.2 at week2, and 16.9 vs. 14.7 at week12, respectively) and DLQI score (6.0 vs. 4.4 at week2, and 9.9 vs. 7.5 at week12, respectively); a similar proportion of patients also achieved PASI50 at week2, and PASI75 and PASI90 at week12, and a DLQI (0/1) at weeks2 and 12. Several significantly different results were reported between subgroups, the majority of which favored patients with special body area involvement. Most patients had psoriasis involvement in a special body area which was associated with worse QoL. Ixekizumab is similarly effective in reducing disease severity and improving QoL in patients with plaque psoriasis across different special body areas.

Real-life data over 36 weeks of guselkumab treatment in psoriasis patients: A single-center study from Turkey.

Psoriasis is an important health problem responsible for morbidity and workforce loss. In recent years, anti-IL-23 drugs have become essential in psoriasis treatment. This study aimed to investigate the efficacy and safety of guselkumab therapy, recently used in Turkey, by examining real-life data over 36 weeks. A total of 39 psoriasis patients (>18 years old) who received guselkumab treatment between December 2021 and December 2022 in the dermatology department of our hospital were included in the study. Patients" ages, sexes, body mass index (BMI), comorbidities, duration of illness, drugs used before guselkumab treatment, clinical response to guselkumab treatment, and side effects, if any, were recorded. Psoriasis Area and Severity Index (PASI) scores at baseline and Weeks 4, 12, 24, and 36 were evaluated, as well as the Dermatology Life Quality Index (DLQI) at the beginning and end of the study. The PASI scores at Weeks 4, 12, 24, and 36 and the DLQI at Week 36 decreased statistically compared with baseline (p < 0.05). The PASI score at baseline and Weeks 4, 24, and 36 did not differ between groups based on IL-17 use (p > 0.05). No significant correlation was observed between BMI, disease duration, and PASI scores at baseline and Weeks 4, 12, 24, and 36. No side effects were observed in any of the patients during treatment. This study includes real-life data on the use of guselkumab therapy for psoriasis in the Turkish population. Based on the results, guselkumab is a highly effective and safe treatment.

Development of Betulin-Loaded Nanostructured Lipid Carriers for the Management of Imiquimod-Induced Psoriasis.

Psoriasis is a complex and persistent autoimmune skin disease. The present research focused on the therapeutic evaluation of betulin-loaded nanostructured lipid carriers (BE-NLCs) towards managing psoriasis. The BE-NLCs were synthesized using the emulsification cum solidification method, exhibiting a spherical shape with a particle size of 183.5±1.82nm and a narrow size distribution window (PDI: 0.142±0.05). A high zeta potential -38.64±0.05mV signifies the relative stability of the nano-dispersion system. BE-NLCs show a drug loading and entrapment efficiency of 47.35±3.25% and 87.8±7.86%, respectively. In vitro release study, BE NLCs show a cumulative percentage release of 90.667±5.507% over BE-sol (57.334±5.03%) and BD-oint (42±4.58%) for 720min. In an ex vivo 24-h permeation study, % cumulative amount permeated per cm2 was found to be 55.667±3.33% from BE-NLCs and 32.012±3.26% from BE-sol, demonstrating a better permeability of 21.66% when compared to the standard formulation BD-oint. The in vivo anti-psoriatic activity in the IMQ-induced model shows topical application of BE-sol, BE-NLCs, and BD-oint resulted in recovery rates of 56%, 82%, and 65%, respectively, based on PASI (Psoriasis Area and Severity Index) score. Notably, BE-NLCs demonstrated a more significant reduction in spleen mass, indicating attenuation of the local innate immune system in psoriatic mice. Reductions in TNF-α, IL-6, and IL-17 levels were observed in both BE-sol and BE-NLCs groups compared to the disease control (DC) group, with BE-NLCs exhibiting superior outcomes (74.05%, 44.76%, and 49.26% reduction, respectively). Soy lecithin and squalene-based NLCs could be better carrier system for the improvement of the therapeutic potential of BE towards management of psoriasis.

Employing zero-inflated beta distribution in an exposure-response analysis of TYK2/JAK1 inhibitor brepocitinib in patients with plaque psoriasis.

Brepocitinib is an oral selective dual TYK2/JAK1 inhibitor and based on its cytokine inhibition profile is expected to provide therapeutic benefit in the treatment of plaque psoriasis. Efficacy data from a completed Phase 2a study in patients with moderate-to-severe plaque psoriasis were utilized to develop a population exposure-response model that can be employed to inform dose selection decisions for further clinical development. A modeling approach that employs the zero-inflated beta distribution was used to account for the bounded nature and distributional characteristics of the Psoriasis Area and Severity Index (PASI) score data. The developed exposure-response model provided an adequate description of the observed PASI scores across all the treatment arms tested and across both the induction and maintenance dosing periods of the study. In addition, the developed model exhibited a good predictive capacity with regard to the derived responder metrics (e.g., 75%/90%/100% improvement in PASI score [PASI75/90/100]). Clinical trial simulations indicated that the induction/maintenance dosing paradigm explored in this study does not offer any advantages from an efficacy perspective and that doses of 10, 30, and 60mg once-daily may be suitable candidates for clinical evaluation in subsequent Phase 2b studies.

Real-world Safety and Efficacy of Risankizumab in Psoriatic Patients: A Multicenter, Retrospective, and Not-interventional Study

Background and objectiveRisankizumab – a humanized monoclonal antibody that targets the p19 subunit of IL-23 – has been recently approved to treat moderate-to-severe plaque psoriasis. Real-world data based on a representative pool of patients are currently lacking. ObjectiveTo assess the mid- and long-term safety and efficacy profile of risankizumab in patients with moderate-to-severe psoriasis in the routine clinical practice. MethodsThis was a retrospective and multicenter study of consecutive psoriatic patients on risankizumab from April 2020 through November 2022. The primary endpoint was the number of patients who achieved a 100% improvement in their Psoriasis Area and Severity Index (PASI) (PASI100) on week 52. ResultsA total of 510 patients, 198 (38.8%) women and 312 (61.2%) men were included in the study. The mean age was 51.7±14.4 years. A total of 227 (44.5%) study participants were obese (body mass index [BMI] >30kg/m2). The mean baseline PASI score was 11.4±7.2, and the rate of patients who achieved PASI100 on week 52, 67.0%. Throughout the study follow-up, 21%, 50.0%, 59.0%, and 66% of the patients achieved PASI100 on weeks 4, 16, 24, and 40, respectively. The number of patients who achieved a PASI ≤2 was greater in the group with a BMI ≤30kg/m2 on weeks 4 (P=.04), 16 (P=.001), and 52 (P=.002). A statistically significantly greater number of patients achieved PASI100 in the treatment-naïve group on weeks 16 and 52 (P=.001 each, respectively). On week 16 a significantly lower number of participants achieved PASI100 in the group with psoriatic arthropathy (P=.04). Among the overall study sample, 22 (4.3%) patients reported some type of adverse event and 20 (3.9%) discontinued treatment. ConclusionsRisankizumab proved to be a safe and effective therapy for patients with moderate-to-severe psoriasis in the routine clinical practice.

Efficacy and safety of tildrakizumab in elderly patients: real-world multicenter study (ESTER – study)

Purpose of the article: Interleukin-23 inhibitors, such as tildrakizumab, have emerged as safe and effective options for the management of psoriasis. Yet their efficacy in elderly patients (aged 65 years or more), particularly in those with difficult-to-treat areas involvement, remains insufficiently explored. We conducted this real-life retrospective multicentric observational study to assess the effectiveness of tildrakizumab in elderly patients with moderate-to-severe psoriasis, with involvement of difficult-to-treat areas.Materials and methods: We enrolled forty-nine patients aged 65 years old or more (mean age 73.1 ± 6.0), all treated with tildrakizumab for at least 28 weeks. The effectiveness of tildrakizumab was assessed by Static Physician’s Global Assessment of Genitalia (sPGA-G), fingernail-PGA (f-PGA), palmoplantar PGA (pp-PGA), scalp-specific PGA (sc-PGA), and Psoriasis Area and Severity Index (PASI) scores.Results: Significant improvements in PASI scores were observed within 28 weeks of treatment, with 77.5%, 60%, and 45.2% of patients achieving PASI75, PASI90, and PASI100, respectively. The mean PASI decreased significantly from baseline (13.6 ± 9.9) to 1.3 ± 1.7 at week 28. More than 90% of patients had clear sPGA-G and pp-PGA scores and over 70% had clear f-PGA and sc-PGA scores after 28 weeks.Conclusions: Our findings suggest that tildrakizumab could be a valuable option for the treatment of elderly patients, including those with difficult-to-treat areas involvement.

Effect of stearyl alcohol on imiquimod-induced psoriasis-like skin inflammation in mice.

Psoriasis is a chronic inflammatory skin disease. Topical medicines are the preferred treatment for mild to moderate psoriasis, but the effect of excipients used in semi-solid preparations on psoriasis-like skin inflammation is not fully understood. In the present study, we investigated the effect of stearyl alcohol, a commonly used excipient, on imiquimod (IMQ)-induced psoriasis-like skin inflammation in mice. Psoriasis-like skin inflammation was induced by topical IMQ treatment on the back of mice. Skin lesion severity was evaluated by using psoriasis area and severity index (PASI) scores. The skin sections were stained by haematoxylin-eosin and immunohistochemistry. Stearyl alcohol (20% in vaseline) treatment significantly reduced the IMQ-induced increase of PASI scores and epidermal thickness in mice. IMQ treatment increased the number of Ki67- and proliferating cell nuclear antigen (PCNA)-positive cells in the skin, and the increases were inhibited by stearyl alcohol (20% in vaseline) treatment. Stearyl alcohol treatment (1%, 5%, 10% in vaseline) dose-dependently ameliorated IMQ-induced increase of PASI scores and epidermal thickness in mice. Hexadecanol (20% in vaseline), stearic acid (20% in vaseline) and vaseline treatment had no significant effect on IMQ-induced psoriasis-like skin inflammation in mice. In conclusion, stearyl alcohol has the effect of improving IMQ-induced psoriasis-like skin inflammation in mice.

An Oral Interleukin-23–Receptor Antagonist Peptide for Plaque Psoriasis

BackgroundThe use of monoclonal antibodies has changed the treatment of several immune-mediated inflammatory diseases, including psoriasis. However, these large proteins must be administered by injection. JNJ-77242113 is a novel, orally administered interleukin-23–receptor antagonist peptide that selectively blocks interleukin-23 signaling and downstream cytokine production.MethodsIn this phase 2 dose-finding trial, we randomly assigned patients with moderate-to-severe plaque psoriasis to receive JNJ-77242113 at a dose of 25 mg once daily, 25 mg twice daily, 50 mg once daily, 100 mg once daily, or 100 mg twice daily or placebo for 16 weeks. The primary end point was a reduction from baseline of at least 75% in the Psoriasis Area and Severity Index (PASI) score (PASI 75 response; PASI scores range from 0 to 72, with higher scores indicating greater extent or severity of psoriasis) at week 16.ResultsA total of 255 patients underwent randomization. The mean PASI score at baseline was 19.1. The mean duration of psoriasis was 18.2 years, and 78% of the patients across all the trial groups had previously received systemic treatments. At week 16, the percentages of patients with a PASI 75 response were higher among those in the JNJ-77242113 groups (37%, 51%, 58%, 65%, and 79% in the 25-mg once-daily, 25-mg twice-daily, 50-mg once-daily, 100-mg once-daily, and 100-mg twice-daily groups, respectively) than among those in the placebo group (9%), a finding that showed a significant dose–response relationship (P<0.001). The most common adverse events included coronavirus disease 2019 (in 12% of the patients in the placebo group and in 11% of those across the JNJ-77242113 dose groups) and nasopharyngitis (in 5% and 7%, respectively). The percentages of patients who had at least one adverse event were similar in the combined JNJ-77242113 dose group (52%) and the placebo group (51%). There was no evidence of a dose-related increase in adverse events across the JNJ-77242113 dose groups.ConclusionsAfter 16 weeks of once- or twice-daily oral administration, treatment with the interleukin-23–receptor antagonist peptide JNJ-77242113 showed greater efficacy than placebo in patients with moderate-to-severe plaque psoriasis. (Funded by Janssen Research and Development; FRONTIER 1 ClinicalTrials.gov number, NCT05223868.)

Evaluating the efficacy and mechanisms of Hua-Zhuo-Ning-Fu-Decoction on psoriasis using integrated bioinformatics analysis and metabolomics

Ethnopharmacological relevanceHua Zhuo Ning Fu Decoction (HZD) is an empirical prescription from traditional Chinese medicine that shows excellent clinical results for psoriasis patients. Uncertainty lingered over HZD's potential anti-psoriasis mechanisms. Aim of the studyThe study's objective is to investigate the pharmacological processes and therapeutic effects of HZD on psoriasis. Materials and methodsIn the initial phase of the study, an investigation was conducted to assess the effects of HZD on psoriasis-afflicted mice using an imiquimod (IMQ)-induced murine model. The experimental mice were randomly allocated to different groups, including the IMQ-induced model group, the control group, the HZD therapy groups with varying dosage levels (low, medium, and high), and Dexamethasone (DEX, the positive control medicine) group. Bioinformatics analysis and molecular docking were subsequently employed to identify the primary components and molecular targets associated with the therapeutic action of HZD in the context of psoriasis. Additionally, to find the impacts on metabolite regulation, plasma metabolomics based on ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-QTOF/MS) was used. It's interesting to note that the combined mechanisms from metabolomics were examined in tandem with the targets. In vivo tests were the last step in validating the potential mechanism. Throughout the trial, the following data were recorded: body weight, psoriasis area and severity index (PASI). The molecular targets connected to HZD's anti-psoriasis activities were revealed using histological examination, western blot (WB), and ELISA investigation. ResultsIn mice induced with IMQ, HZD shown good anti-psoriasis effects in terms of PASI score and epidermal acanthosis. 95 HZD targets and 77 bioactive chemicals connected to psoriasis were found by bioinformatics research; of these, 7 key targets (EPHX2, PLA2G2A, TBXAS1, MAOA, ALDH1A3, ADH1A, and ADH1B) were linked to the mechanisms of HZD, the combination degree of which was finally expressed by the score of docking. In addition, HZD regulated nine metabolites. In line with this, HZD modified three metabolic pathways. Additionally, a combined examination of 7 key targets and 9 metabolites suggested that the metabolism of arachidonic acid might be the key metabolic route, which was identified by ELISA analysis. The in vivo investigation shown that HZD could control cytokines associated to inflammation (IL-10, TGF-β, IL-17A, and IL-23), as well as important antioxidant system markers (ROS, GSH, and MDA). Moreover, HZD controlled iron levels and the expression of ferroptosis-related proteins (ACSL4 and GPX4), suggesting that ferroptosis played a crucial role in this process. ConclusionsOur findings demonstrated the whole mechanism and anti-psoriasis effectiveness of HZD, which will promote its clinical application and aid in the investigation of new bioactive components of HZD against psoriasis.

Ayurvedic management of Plaque Psoriasis - A Case Study

Psoriasis is a chronic inflammatory disease affecting mainly in skin and joint. In Ayurveda, under the umbrella of Kushtha all skin diseases are described. In management of Psoriasis Ayurvedic system of medicine is giving good results. The main line of treatment of skin diseases in Ayurveda is repeated Samshodhana (purificatory therapies) along with Samshamana (palliative therapies). Three assessments were done before and after treatment on scoring of Dermatology Life Quality Index (DLQI), Psoriasis Disability Index (PDI) and PASI score. Score of the patient was 83% before treatment and 16% after treatment and 10% after follow up on Dermatology Life Quality Index (DLQI), 86% before treatment and 65% after treatment and 41% after follow up on Psoriasis Disability Index (PDI) and 35.5% before treatment, 10.2% after treatment and 8% after follow up in PASI (Psoriasis Area and Severity Index). This case study wants to substantiate the effectiveness of Ayurvedic treatment in the management of Plaque psoriasis.