PASI Reduction Research Articles

A 3-Year Experience with Tildrakizumab Treatment for Patients with Plaque Psoriasis in Clinical Practice.

The efficacy and safety of tildrakizumab for the treatment of plaque psoriasis were demonstrated by randomized clinical studies, but the reappraisal of prolonged experiences in the clinical practice helps to optimize the use of this biologic drug. The aim of this study was to evaluate the long-term efficacy of tildrakizumab in patients with moderate-to-severe psoriasis in the real world. This is a long-term retrospective observational study in a real-life setting. Overall, 136 adult patients with moderate-to-severe plaque psoriasis and treated with tildrakizumab were included. One hundred percent reduction of Psoriasis Area Severity Index (PASI100) was reached by 21.7% of patients at 4 weeks of therapy and by 51.2% at week 16, and the proportion of patients with this improvement was between 66.9% and 64.5% from 36 weeks to 3 years. The mean PASI of the cohort progressively improved from 12.6 at baseline to 1.8 at week 36 and was stable at 1 year, 2 years and 3 years. We could not confirm a previous observation that patients naïve to biologic had a better response, but we observed that those with a short history of psoriasis had a higher probability of 90% PASI reduction (PASI90) or PASI 100 within 36 weeks, suggesting that early treatment could be useful. This long-term observation in the real life of patients with moderate-to-severe plaque psoriasis receiving tildrakizumab 100 mg showed that PASI100 can be obtained in a high proportion of patients by week 36 and be maintained for up to 3 years.

Development and evaluation of methotrexate-loaded nanoemulsion formulation for topical treatment of psoriasis.

Psoriasis is a chronic inflammatory disease that is becoming widespread and is associated with many kinds of additional severe diseases. The present study aimed to develop a methotrexate-loaded almond oil-based nanoemulsion formulation (MTX NE) for topical administration. The drug-loaded nanoemulsion formulation was prepared by high shear homogenization technique. The formulation's stability, as well as other physical and chemical characteristics, including entrapment effectiveness, drug release kinetics, skin permeability, skin irritation, and in vivo evaluation of the optimized formulation, was assessed. Additionally, imiquimod-induced psoriasis in rats was employed to investigate the efficacy of MTX NE against skin disorders. The MTX NE formulation was developed with a particle size of 18.74 ± 9.748nm, a polydispersity index (PDI) of 0.198 ± 0.01, and an average entrapment efficiency of 79.65 ± 3.84%. The release kinetics model estimates 81.08% drug release at pH 5.5 after 24h. The major layers of the skin, the epidermis, and dermis were successfully fluidized by the optimized MTX NE formulation, as shown by FTIR results, most likely enhancing drug retention and permeability. However, since Tween 80 and PEG 400 are well-known penetration enhancers, their application greatly accelerates these effects. Permeation data indicate that after 24h, methotrexate was released from the nano-emulsion at 76.83 ± 4.98g/cm2 with a flux rate of 2.385 ± 0.61µg/cm2/h. The in vivo study conducted on rabbit skin showed that the enhanced skin penetration of the prepared MTX-loaded nanoemulsion formulation does not cause any structural modifications in the inter-cellular lipid layers of the stratum corneum. Rabbits used in the in vivo anti-psoriatic investigation demonstrated that MTX NE produced a 95% reduction in PASI. The pharmacokinetic profile revealed that the Cmax, Tmax, and t1/2 values were 8.63µg/mL, 12.5h, and 17.77 ± 2.21h, respectively. These findings suggest that the formulation MTX NE is effective in treating psoriasis and may reduce psoriasis symptoms.

IFN-γ, IL-17A, IL-4, and IL-13: Potential Biomarkers for Prediction of the Effectiveness of Biologics in Psoriasis Patients.

Biologics are widely used to treat moderate-to-severe psoriasis. However, we have unmet needs for predicting individual patient responses to biologics before starting psoriasis treatment. We investigate a reliable platform and biomarkers for predicting individual patient responses to biologics. In a cohort study between 2018 and 2023 from a referral center in Taiwan, twenty psoriasis patients with or without psoriatic arthritis who had ever experienced two or more biologics were enrolled. Peripheral blood mononuclear cells obtained from these patients were treated with Streptococcus pyogenes and different biologics. The PASI reduction rate was strongly correlated with the reduction rate in the IL-13 level (p = 0.001) and the ratios of IFN-γ to IL-13 (p < 0.001), IFN-γ to IL-4 (p = 0.019), and IL-17A to IL-13 (p = 0.001). The PASI reduction difference was strongly correlated with the difference in the IFN-γ level (p = 0.002), the difference in the ratios of IFN-γ to IL-4 (p = 0.041), the difference in the ratios of IFN-γ to IL-13 (p = 0.006), the difference in the ratios of IL-17A to IL-4 (p = 0.011), and the difference in the ratios of IL-17A to IL-13 (p = 0.029). The biomarkers IFN-γ, IL-13, IFN-γ/IL4, IFN-γ/IL13, IL-17A/IL-4, and IL-17A/IL-13 are representative of the effectiveness of psoriasis treatment.

Effects of Different Therapeutic Approaches on Redox Balance in Psoriatic Patients.

Given that oxidative stress represents an important etiological factor in the pathogenesis of psoriasis, the aim of this study was to assess the effects of different therapeutic approaches, methotrexate, secukinumab, and ustekinumab on systemic oxidative stress biomarkers in psoriatic patients. This study involved 78 psoriatic patients, divided into the group treated with methotrexate (23 patients), secukinumab (28 patients), and ustekinumab (27 patients), and 15 healthy controls. Oxidative stress biomarkers (index of lipid peroxidation measured as TBARS, nitrites (NO2-), superoxide anion radical (O2-), and hydrogen peroxide (H2O2)) and antioxidative defense system (superoxide dismutase (SOD) activity, catalase (CAT) activity, and reduced glutathione (GSH)) were determined spectrophotometrically from the blood before the initiation of therapy in 16th, 28th, and 52nd week. O2- and SOD showed the most prominent changes comparing the psoriatic patients and healthy controls. CAT activity was significantly lower in psoriatic patients, and methotrexate induced a further decline in CAT activity. Ustekinumab induced a significant increase in GSH level after 52 weeks of treatment, while methotrexate reduced GSH. All applied therapeutic options induced a reduction in PASI, BSA, DLQI, and EARP. Biological drugs exert more pronounced antioxidant effects compared to methotrexate, which is most clearly observed in the values of O2- and SOD.

Circulating Monocytes Are Predictive and Responsive in Moderate-to-Severe Plaque Psoriasis Subjects Treated with Apremilast

Monocytes play a critical role in the inflammation associated with psoriasis, and their abnormalities have been reported as biomarkers of cardiovascular event risk, a psoriasis comorbidity. Monocytic cells in chronic inflammatory disorders express elevated levels of cAMP phosphodiesterase. Restoring cAMP levels using the oral cAMP phosphodiesterase-4 inhibitor, apremilast, improves clinical outcomes for a subset of patients with psoriasis. We asked whether aberrant monocyte subsets or transcriptomic pathways can function as biomarkers of psoriasis endotypes that can predict enhanced clinical responses to cAMP phosphodiesterase inhibition. A 16-week open-label study of 22 patients with monocyte flow cytometric and transcriptomic analysis was performed. Subjects with elevated hyperadhesive monocyte doublets at baseline were more likely to be responders to apremilast (P < .0001); 82% of subjects with elevated hyperadhesive monocyte doublets achieved 50% reduction in PASI compared with 46% in those without elevated doublets. We observed a significant reduction in hyperadhesive monocyte-containing doublets and monocyte-platelet aggregates, suggesting an effect of apremilast on the adhesiveness of blood monocytes during chronic inflammation. Monocyte differentially expressed gene transcripts predictive of clinical response uncovered pharmacoendotypes with distinct patterns of nucleotide metabolism, energetics, and differentiation. Further study to understand the basis of drug responsiveness and to develop an apremilast psoriasis treatment algorithm using monocyte-refined gene expression is required to validate and become practical in clinical use, offering patients a test that personalizes their likelihood of clinical response.

Efficacy and safety of apremilast in pediatric patients with moderate-to-severe plaque psoriasis: 16-week results from SPROUT, a randomized controlled trial

Approved systemic treatment options are limited for pediatric patients with moderate to severe plaque psoriasis. To assess the efficacy and safety of apremilast over 16weeks in pediatric patients with plaque psoriasis. SPROUT (NCT03701763) was a phase 3, multicenter, randomized, double-blind, placebo-controlled study of apremilast in patients aged 6-17years with moderate-to-severe psoriasis (Psoriasis Area and Severity Index [PASI] ≥12, body surface area ≥10%, static Physician Global Assessment [sPGA] ≥3) inadequately controlled by/inappropriate for topical therapy. Patients were stratified by age group and randomized (2:1) to apremilast (20 or 30mg BID based on weight) or placebo for 16weeks, followed by apremilast extension to 52weeks. Of 245 patients randomized (apremilast: 163; placebo: 82), 221 (90%) completed the double-blind phase (apremilast: 149; placebo: 72). Significantly more patients achieved sPGA response and ≥75% reduction in PASI with apremilast than placebo, regardless of baseline age, weight, or disease severity. No new safety signals were observed. Sample size of subgroup analyses. Improvements in global disease activity and skin involvement were significantly greater in pediatric patients treated with apremilast versus placebo. Adverse events were consistent with the known apremilast safety profile.

Comparison of efficacy of Methoterexate versus Acitretin in the treatment of chronic plaque psoriasis

Objective: To compare the efficacy of methotrexate versus acitretin in the treatment of chronic plaque psoriasis Method: Randomized controlled Trial conducted in Dermatology Department, Services Hospital Lahore, on 60 patients after informed consent, divided into two groups. Group A given methotrexate 0.30.5mg/kg orally and group B given acitretin 0.4mg/kg orally. Efficacy was ascertained by reduction in PASI score, calculated at baseline and at the 12 weeks. Results:Patients of Group A achieved a reduction in PASI score from baseline 13.13±2.047 to 6.20±2.024 (efficacy 76.7%) while in Group B, PASI score dropped from 13.53±2.047 to 7.00±1.857 (efficacy 56.7%). Adverse effects for both groups were minimal and as expected. Conclusion: Both methotrexate and acitretin are highly effective drugs in treating chronic plaque psoriasis. However, methotrexate shows greater efficacy and faster reduction in PASI as compared to acitretin.

Real-World Implementation and Outcomes of Adalimumab Therapeutic Drug Monitoring in Psoriasis: A National Specialized Center Experience

Serum adalimumab concentration is a biomarker of treatment response but therapeutic drug monitoring (TDM) is yet to be implemented in routine psoriasis care. We incorporated adalimumab TDM in a national specialised psoriasis service and evaluated it using the RE-AIM implementation science framework. We undertook pre-implementation planning (validating local assays) and implementation interventions targeted to patients (pragmatic sampling at routine reviews), clinicians (introduction of TDM protocol) and healthcare systems (adalimumab TDM as a key performance indicator). Over 5-months, 170 of 229 (74%) individuals treated with adalimumab received TDM. Clinical improvement following TDM-guided dose escalation occurred in 13 of 15 (87%) non-responders with serum drug concentrations <8.3μg/ml (median PASI reduction 3.2 [IQR 2.2-8.2] after 23.4 weeks), and in all non-responders who had TDM-guided switch in biologic due to supratherapeutic drug concentrations (>8.3μg/mL; n=2) or positive anti-drug antibody (n=2) (PASI reduction 7.8 [7.5-12.9] after 20.0 weeks). Proactive TDM led to dose reduction in 5 individuals with clear skin and sub- or supra-therapeutic drug concentrations; 4 (80%) sustained clear skin after 50 [42-52] weeks. Adalimumab TDM based on pragmatic serum sampling is clinically viable and may lead to patient benefit. Context-specific implementation interventions and systematic implementation assessment may bridge the biomarker research-to-practice gap.

Tildrakizumab in Complex Psoriatic Patients: An Experience in Emilia-Romagna (Italy).

IL-23 inhibitors are the latest class of biologic drugs approved for moderate-to-severe psoriasis. to investigate real-life safety and efficacy of tildrakizumab. demographic data, medical history, psoriasis disease history, PASI, DLQI, BSA, NAPSI were recorded at weeks 0, 12, 24, 36. PASI, BSA, DLQI and NAPSI all decreased rapidly during the 36 week follow-up period. PASI score reduced from 12.28 to 4.65 by week 12, followed by a further decrease to 1.18 at week 36 Multiple logistic regression showed that smoking, BMI ≥30, ≥3 comorbidities, previous systemic traditional or biologic drugs, psoriatic arthritis nor difficult-to-treat areas influenced the reduction of PASI and NAPSI scores during treatment with tildrakizumab (P > .05). we assessed a good performance of tildrakizumab in patients with multiple comorbidities, multi-failure, elderly patients, and in subjects with psoriatic arthritis.

Secukinumab long-term efficacy and safety in psoriasis through to year 5 of treatment: results of a randomized extension of the phase III ERASURE and FIXTURE trials.

In the long-term extension study of the ERASURE and FIXTURE trials, the efficacy of secukinumab (a fully human anti-interleukin-17A monoclonal antibody) was demonstrated to have been maintained through to year 3 of treatment in moderate-to-severe plaque psoriasis. To assess the efficacy and safety of secukinumab through to year 5 of treatment in moderate-to-severe plaque psoriasis. Responders with ≥ 75% improvement in Psoriasis Area and Severity Index (PASI 75) from two core trials - ERASURE and FIXTURE - were randomized 2 : 1 at year 1 (end of core trials) to either the same dose (300 or 150 mg, continuous treatment) or placebo (treatment withdrawal) every 4 weeks, until year 3 or relapse (> 50% reduction in maximal PASI from core study baseline). Partial responders (achieving PASI 50 but not PASI 75) at year 1 continued at the same dose as in the core trials. At year 3, all patients received open-label secukinumab treatment, with those on secukinumab 300 mg continuing on their dose, while those on secukinumab 150 mg or placebo received secukinumab 150 or 300 mg based on the physician's discretion. The study is registered on ClinicalTrials.gov with the identifier NCT01544595. Most patients randomized to placebo at year 1 relapsed, but the response was rapidly recaptured upon reinitiation of treatment. PASI responses were sustained with secukinumab through to year 5. The PASI responses for the 300 mg responders + partial responders group at year 1 (PASI 75/90/100: 86.8%/72.8%/45.9%) trended downwards until year 3 (PASI 75/90/100: 82.3%/58.4%/32.7%) and then remained stable through year 4 (PASI 75/90/100: 83.3%/60.1%/32.2%) until year 5 (PASI 75/90/100: 81.1%/62.8%/35.1%). Dermatology Life Quality Index showed sustained benefit up to year 5. Absolute PASI responses were maintained throughout the study. The most common adverse events (AEs) were infections and infestations, nasopharyngitis, and upper respiratory tract infections (URTIs). The overall exposure-adjusted incidence rate (EAIR; with 95% confidence interval) for all AEs was 139.9 (130.3-149.9). EAIRs for Crohn's disease and neutropenia were 0.1 (0.0-0.3) and 0.5 (0.3-0.8), respectively. The 4-year extension of two pivotal phase III trials demonstrated that secukinumab treatment was effective through to year 5 and improved quality of life in patients with moderate-to-severe plaque psoriasis. The most common AEs were infections and infestations, nasopharyngitis, and URTIs. The safety profile was consistent with that in the secukinumab phase II/III clinical development programme.

Issues of use of hepatoprotectors in psoriasis: Indications and effectiveness

The pathology of the hepatobiliary system in psoriasis may be the result of taking hepatotoxic drugs, the result of a systemic inflammatory process. In this connection, it is necessary to consider the issue of including hepatoprotective drugs in psoriasis treatment regimens. There were 69 patients under observation, which, depending on the severity and prescribed treatment, were divided into 4 groups. In the B1A subgroup, a 75% reduction in PASI was observed in all patients, with PASI100 reaching 87.5% of patients. In subgroup 1B, a 75% decrease in PASI was observed in 87.5% of patients, while PASI100 reached 68.7% of patients. The DIQI index reduced in the 1A subgroup by 72.9%, in the 1B subgroup – by 66.3%. All patients of group 1 were diagnosed with non-alcoholic fatty liver disease. After therapy, in patients of subgroup 1A (therapy included a course of phosphogliv), the number of transaminases signifcantly decreased, in subgroup 1B there was no dynamics. In subgroup 2A, a 75% decrease in PASI was observed in 90% of patients, while PASI100 reached 60.0% of patients. In subgroup 2B, a 75% decrease in PASI was observed in 70.6% of patients, while PASI100 reached 47.1% of patients. The DIQI index reduced in the 2A subgroup by 77.0%, in the 2B subgroup – by 60.2%. The inclusion of phosphogliv in the therapeutic complex can increase the effectiveness of the treatment and reduce the risk of developing druginduced liver damage against the background of the use of potentially hepatotoxic drugs.

Data Mining and Meta-Analysis of Psoriasis Based on Association Rules.

Psoriasis is a common chronic and recurrent disease in dermatology, which has a great impact on the physical and mental health of patients. Meta-analysis can evaluate the effectiveness and safety of defubao in the treatment of psoriasis vulgaris. This article observes psoriasis skin lesions treated with topical defubao and the changes in blood vessels under dermoscopy. Considering that the Apriori algorithm and the existing improved algorithm have the problems of ignoring the weight and repeatedly scanning the database, this paper proposes a matrix association rule method based on random forest weighting. This method uses the random forest algorithm to assign weights to each item in the data set, and introduces matrix theory to convert the transaction data set into a matrix form and store it, thereby improving operating efficiency. This article included 11 studies, of which 7 studies used the indicator “Researcher's Overall Assessment” (IGA) to evaluate the efficacy, 5 studies used the “Patient Overall Assessment” (PGA) as the efficacy evaluation index, and Loss Area and Severity Index (PASI) was used as an observation index to evaluate the efficacy. Seven studies conducted safety comparisons. In this paper, IGA and PGA were used as evaluation indicators. The treatment effect of the defubao group was better than the calcipotriol group and the betamethasone group. The differences were statistically significant. The effect of the Fubao treatment for 8 weeks is significantly better than that of 4 weeks and 2 weeks, and the differences are statistically different. Using PASI as the evaluation index, a descriptive study was carried out, and it was found that after 4 weeks of treatment for psoriasis vulgaris, the average PASI reduction rate of patients was higher than that of the calcipotriol group and the betamethasone group. The safety evaluation found that after 8 weeks of treatment, the incidence of adverse events in the defubao group was significantly lower than that in the calcipotriol group.

Biological therapy in patients with psoriasis: What we know about the effects on renal function.

Psoriasis is a chronic inflammatory dermatosis affecting 2%-3% of the general population. The link between psoriasis and renal dysfunction has been investigated, demonstrating a common pro-inflammatory pathogenesis. This study is aimed at evaluating renal function in patients with moderate-to-severe chronic plaque psoriasis treated with biological therapy. We analyzed 92 patients, correlating PASI and serum creatinine levels at baseline, after 6 months and after 1 year of continuous treatment with biological therapy. Data were analyzed using paired t-test and the linear mixed model for PASI and serum creatinine levels correlation, whereas the analysis of variances (ANOVA) was used for creatinine levels assessment between the baseline, the 6-months and, 1-year later evaluation. We observed a significant mean decrease in comparing serum creatinine levels after 1 year of biological therapy (p < 0.001). Interestingly, PASI reduction is correlated with creatinine decrease, and the renal function improvement is greater when complete psoriasis remission is attained. Our data suggest that a drop in systemic inflammation, secondary to biological therapy administration, might improve renal function. Future research is needed to confirm and expand our findings.

Liangxue Jiedu Formula Improves Psoriasis and Dyslipidemia Comorbidity via PI3K/Akt/mTOR Pathway.

The pathological mechanism of psoriasis and dyslipidemia comorbidity is unclear, and there are few reports on therapy. By establishing an animal model of ApoE−/− mice induced by imiquimod (IMQ), we explored the effects of Liangxue Jiedu formula (LXJDF), a traditional Chinese herb medicine, on psoriasis and dyslipidemia comorbidity through PI3K/Akt/mTOR pathway. The experiment was divided into a control group, a model group, an LXJDF high-dose group, an LXJDF low-dose group, and a positive drug (atorvastatin) group. Each group of mice was given continuous oral administration once a day. After 3 weeks, the mice dorsal skins were smeared with 62.5 mg of 5% IMQ cream for five consecutive days and continued to be given the corresponding drugs. We observed the effects of LXJDF on skin lesion changes, PASI score, pathological characteristics, blood lipid levels (TC, TG, LDL, HDL, and oxLDL), liver pathology, inflammatory factors in the skin, and the protein expression of PI3K/Akt/mTOR pathway in both the skin and liver. The results showed that LXJDF could significantly improve the psoriasiform skin lesions of IMQ-induced ApoE−/− mice, including the reduction of PASI, thinning of epidermal thickness, inhibition of hyperkeratosis and parakeratosis, and inflammatory infiltration in the dermis, and reduce lipid accumulation in the epidermal. LXJDF could regulate blood lipid levels, reduce liver inflammation, and protect the liver. LXJDF could significantly decrease the gene expressions of inflammatory factors IL-17A, IL-23, IL-6, and TNF-α in the skin. LXJDF showed specific inhibition of PI3K, Akt, mTOR protein, and its phosphorylation expressions. In conclusion, LXJDF exerts an intervention effect on psoriasis and dyslipidemia comorbidity via PI3K/Akt/mTOR and its phosphorylation pathway.

The Impact of ANxA6 Gene Polymorphism on the Efficacy of Methotrexate Treatment in Psoriasis Patients

Background: There are great interindividual variations in the clinical efficacy of methotrexate (MTX) treatment and patients’ genetic background seems promising in its explanation. Objectives: The study aimed to test whether the polymorphism of annexin A6 (ANxA6) gene, a susceptibility factor for psoriasis, was associated with the clinical response to MTX therapy. Methods: A total of 325 patients enrolled in the study received oral MTX treatment, of whom 310 completed the 1-year study and performed the genotype analysis. They were defined as responders (a reduction of Psoriasis Area and Severity Index [PASI] score ≥75%) and nonresponders (a reduction of PASI <50%) compared to baseline after 12 weeks of short-time therapy. On 1-year treatment, they were defined as responders if they achieved PASI75 and absolute PASI ≤3, otherwise as nonresponders. The genotypes of 4 single-nucleotide polymorphisms (SNPs) in the ANxA6 gene were verified using the Sequenom platform. Potential predictors associated with the treatment outcome of MTX were assessed by binary logistic regression. Results: We found significant associations for the ANxA6 SNPs of rs11960458, rs960709, and rs13168551 with psoriasis severity. Patients with rs11960458 CC genotype and rs960709 GG genotype showed higher percentages of PASI75 and improvement rates of PASI at 12 weeks. And on 1-year treatment, statistical difference occurred in rs11960458 rather than other SNPs compared between responders and nonresponders that the frequency of CC genotype was higher in responders (p = 0.019). After adjustment for potential confounders, patients with rs11960458 TT/CT genotype (at 12 weeks: OR 0.483, 95% CI 0.245–0.951, p = 0.035; at 1 year: OR 0.483, 95% CI 0.280–0.833, p = 0.009) were significantly more likely to not respond to MTX both on the short-term and long-term treatment, while rs960709 and rs13168551 polymorphisms were only associated with the short-term efficacy of MTX (p = 0.018 and p = 0.036, respectively). Conclusions: The CC ge­notype of ANxA6 (rs11960458) was significantly associated with a better response when compared to those patients with the TT/CT genotype, thus being a potential predictor for the clinical efficacy of MTX.

Cytokine Levels of Skin Lesions in Moderate and Severe Psoriasis as Predictors for the Type 4 Fosphodiesterase Inhibitor (Apremilast) Therapy Effectivness

Background.Psoriasis is a widespread skin disorder characterized by cytokines as the main modulators of skin inflammation. A promising psoriasis therapy approach is targeted on cytokine networks by inhibiting the phosphodiesterase 4 (PDE-4). The efficacy and safety of the PDE-4 inhibitor apremilast in psoriasis confirmed in multicenter controlled studies, which, however, are accompanied by reports of unsuccessful therapy cases.Aims to determine early immunological predictors for PDE-4 inhibitor (apremilast) therapy efficacy based on skin lesions cytokines analyzes in patients with moderate to severe psoriasis.Methods.An open, uncontrolled prospective clinical study was performed. Efficacy of apremilast was analyzed by PASI, BSA, sPGA and DLQI. The outcomes at 26 therapy week were compared with the cytokine levels in skin biopsies selected before starting therapy and analyzed using xMAP technology. The multiparameter prognostic model for apremilast therapy effectiveness was developed based on a heterogeneous sequential recognition procedure.Results.The 34 patients with moderate to severe psoriasis were included in the study. According to the clinical outcomes, two comparison groups were formed: high (75% reduction in PASI score or more; n=14) and insufficient (50% reduction in PASI score or less; n=20) apremilast efficiency. Cytokines analyses showed an inverse relationship between the initial anti-inflammatory IL-10 level and the PASI reduction (r=0.37; p0.025). On the other hand, the relationships between pro-inflammatory cytokines IL-1 and IL-6 levels and PASI score at the 26th week of therapy were characterized by positive correlation: r=0.31 (p0.05) and r=0.37 (p0.025), respectively. Based on the data obtained, a predictive model for the apremilast therapy efficiency was developed. The expected predictive values of this model were 86% for a high therapy effectiveness and 60% for an insufficient effectiveness, respectively.Conclusions.The study results for the first time describe the cytokine profiles in the skin lesions in patients, who responded differently to PDE-4 inhibitor therapy. These dada allows to predict the treatment efficacy and give a chance to personalize apremilast usage for the moderate and severe psoriasis treatment.

Association of the Psoriatic Microenvironment With Treatment Response

The ability to predict the efficacy of systemic psoriasis therapy based on immune profiles in skin biopsies could reduce the use of inappropriate treatment and its associated costs and adverse events. It could considerably decrease drug development trial costs as well. To develop a bioinformatic gene signature score derived from skin mRNA to predict psoriasis treatment outcomes for a variety of therapies. In this decision analytical model using 1145 skin samples from different cohorts of 12 retrospective psoriasis studies, samples were analyzed using the CIBERSORT algorithm to define the immune landscape of psoriasis lesions and controls. Random forest classification and principal component analysis algorithms were used to estimate psoriatic microenvironment (PME) signature genes and construct a PME score. Overall, 85 and 421 psoriasis lesions from 1 and 4 independent cohorts were used as discovery and validation studies, respectively. Among them, 157, 71, 89, and 90 psoriasis lesions were treated with etanercept, tofacitinib, adalimumab, and methotrexate, respectively. Number of weeks after treatment initiation when responders and nonresponders could be predicted. Overall, 22 immune cell subtypes formed infiltration patterns that differentiated psoriasis lesions from healthy skin. In psoriasis lesions, the expression of 33 PME signature genes defined 2 immune phenotypes and in aggregate could be simplified to a numerical PME score. A high PME score, characterized by keratinocyte differentiation, correlated with a better treatment response (Psoriasis Area and Severity Index [PASI] reduction, 75.8%; 95% CI, 69.4% to 82.2%; P = .03), whereas a low PME score exhibited an immune activation signature and was associated with a worse response (PASI reduction, 53.5%; 95% CI, 45.3% to 61.7%; P = .03). The PME score at week 4 after treatment initiation correlated with future responder vs nonresponder to treatment status 8 to 12 weeks earlier than PASI reduction for etanercept, methotrexate plus adalimumab, and tofacitinib. The PME score is a biometric score that may predict clinical efficacy of systemic psoriasis therapy in advance of clinical responses. As an application of personalized medicine, it may reduce the exposure of patients with psoriasis to ineffective and expensive therapies.

The effect of the presence of the metabolic syndrome on the efficiency narrow-band uvb ultraviolet radiation (311) in patients with psoriasis

Backgraund: the researchers explain the high prevalence of metabolic syndrome among patients with psoriasis by the development of systemic infl ammation, which is considered as a single pathogenetic mechanism in these pathological conditions. The response of patients with psoriasis with metabolic syndrome to treatment with narrowband therapy is currently insuffi ciently studied. Aims: the study evaluated the effi cacy of narrowband therapy (311 nm) in patients with psoriasis associated with metabolic syndrome. Materials and methods: an objective and instrumental examination was conducted in 72 patients diagnosed with psoriasis vulgaris, after which a course of 20 procedures of narrow-cavity medium-wave ultraviolet irradiation (UFO) with a wavelength of 311 nm (B) was conducted. Patients were divided into 2 groups: patients with psoriasis and patients with psoriasis combined with metabolic syndrome. To assess the eff ectiveness of treatment, the index of the area and severity of psoriasis (PASI), lipid and carbohydrate metabolism; insulin and leptin; proinfl ammatory cytokines —IL-1β, IL-8, TNF-α and anti-infl ammatory cytokine IL-10 before and after the 10th, 20th procedure of UV-B therapy and 3 and 6 months after treatment. Results: а signifi cant decrease in PASI was observed in all patients with psoriasis after 10 procedures of UV-B therapy, but in the group of patients with metabolic syndrome, the PASI index was higher. After 20 procedures, Pasi reduction by more than 50 % was observed in the group of patients with psoriasis without manifestations of metabolic syndrome (р &lt; 0,001). Indicators of lipid and carbohydrate blood metabolism in MS patients decreased (р &lt; 0,05), the eff ect remained up to 6 months. The level of proinfl ammatory cytokines was increased in both groups, but in the group of patients with MS these indicators were higher. In the course of therapy cytokines decreased in both groups, the eff ect was maintained up to six months. On the contrary, IL-10 was reduced in both groups, and increased after our treatment, with the prolongation of the eff ect to 6 months. Conclusions: the appointment of UV-B therapy (311 nm) in patients with psoriasis with metabolic syndrome reduces the eff ectiveness of the course in the long term, which apparently requires repeated courses of narrowband therapy after 6 months.

Comparison of combination therapy of methotrexate with etanercept and etanercept alone in psoriasis in Tertiary care center in South India

Psoriasis is a disorder of chronic nature. But the present day systemic therapies for psoriasis of moderate to severe nature are associated with toxicity and also have a greater level of displeasure in the patients. Hence the current focus for treatment is with intermittent or combination therapy that helps to overcome the loss of effectiveness in treatment over time and decrease the side effects as a result of cumulative toxicities during monotherapy. To assess the effectiveness of oral Methotrexate and Etanercept combination therapy in comparison to Etanercept monotherapy for treatment of moderate to severe plaque type of psoriasis among patients. This was a prospective analytical study conducted in dermatology OPD of Madras Medical College, a tertiary care centre in south India between August 2015 and July 2016. About Forty subjects clinically diagnosed with plaque type of psoriasis based upon the clinical history and morphology of the dermatological lesions were included in this hospital based study depending on inclusion and exclusion criteria and were randomly allocated into two groups. Group C: Combination therapy with oral methotrexate and Etanercept and Group M:Monotherapy with Etanercept alone. All the patients were reviewed every 4 weeks at intervals of 0,4,8 and 12 weeks for complaints and for assessment of clinical response using PASI scoring and DLQI scoring and other investigations. Data was compiled and analyzed with the help of Statistical Package for Social Science (SPSS) Version 20.0. Mean age of the study population was 37.43 ± 10.1 years. Twenty two subjects were males (55%) and eighteen subjects were females (45%). The subjects who received Group C (Methotrexate and Etanercept combination therapy) therapy achieved 75% reduction of PASI in comparison to subjects who received Group M (Etanercept monotherapy) after 8 weeks (30% vs 5%) and after 12 weeks (100% vs 50%). Also Group C showed good response to treatment after 12 weeks in comparison to Group M (85% vs 50%) and this difference in proportion of treatment response between the two groups was statistically significant. Subjects who received Group C showed greater decline (77.4% vs 68.7) in DLQI score after 12 weeks in comparison to subjects who received Group M.

Benefit of a topic ointment as co-medication with biologic drugs for the management of moderate-severe psoriasis: a prospective, observational real-life study.

Psoriasis is a multifactorial chronic inflammatory skin disease characterized by erythemato-squamous lesions with a chronic relapsing course. The desease clinical activity (PASI) and the patient's quality of life (DLQI) are the main elements to assess for setting up a correct therapeutic management. The aim of the study was to evaluate the management of the patient with moderate-severe psoriasis in therapy with biological drugs and to establish the difference in the achievement of PASI 90 and DLQI 0-1 between a group of patients treated with only biological drugs and a group of patients receiving biologic therapy in combination with a topical ointment. We conducted a prospective, observational real-life study enrolling 60 patients with moderate to severe psoriasis and divided in two groups: Group A patients treated with biological drugs, Group B patiens treated with biological drugs in association with an ointment composed of betamethasone, salicylic acid and ammonium sulpho-ichtyolate, applied 2 times a day. PASI and DLQI were evaluated at study beginning (T0) for both study groups, after 12 weeks (T3) for sample in therapy with biological drugs and after 24 weeks (T6) for sample in co-medication therapy. The two-way ANOVA method was used to evaluate the standard deviations (SD): at T3 and T6 Group B obtained a significant PASI reduction and improvement of DLQI (* p value <0.05) compared to Group A. Our study shown that the patients treated with biologics in co-medication with topical therapy reached a significantly higher PASI and DQLI compared with those treated with only biologics. Furthermore we observed that the association with topical oinment showed more efficacy in the treatment of areas such as palm-plantar region, that is often difficult-to-treat region, even for biologic drugs.