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Psoriasis, an inflammatory disease, is largely mediated by T-helper 17 cytokines. We have previously identified the immune system-released activating agent (Israa) as a novel gene that connects the nervous and immune systems. This research aims to investigate the role of the Israa gene in psoriasis in vivo using the imiquimod-induced psoriasis model. We established the model in C57BL/6 wildtype mice, which were then treated with 200 pg/mouse, 400 pg/mouse, or 800 pg/mouse of recombinant ISRAA compared to methotrexate. Subsequently, we also induced psoriasis in Israa-knockout mice to confirm the effect of Israa. Results consistently showed improvement in psoriasis in all groups receiving recombinant ISRAA. The 200 pg/mouse dose eliminated the disease, reduced the cutaneous release of IL-17 to one-third and TNF-α to one-sixth, increased IL-10 release to over 500 pg, completely resolved parakeratosis, decreased epidermal thickness to one-half, and reduced the expression of CD4 and neutrophil elastase in the skin (all p < 0.05). Israa-knockout mice exhibited less severe psoriasis in all scoring, biochemical, and histological parameters compared to wild-type mice (p < 0.05). This study highlights Israa as a crucial molecule in psoriasis and confirms its immunomodulatory role in inflammatory diseases. [ABSTRACT FROM AUTHOR]

Real-world data on anatomically localized psoriasis and its response to systemic therapy across different age-groups and sexes is limited. This study aimed to evaluate the severity and distribution of psoriasis over time in female and male patients receiving systemic therapies, categorized by age within the Swiss psoriasis registry (SDNTT). Patient-data was obtained over 11 years through the SDNTT. The localized Psoriasis Area and Severity Index (locPASI) of the head, trunk, upper and lower extremities was analyzed over two years following the start of systemic non-/biologic treatment. A total of 316 female and 517 male patients were analyzed. Male patients had a higher baseline locPASI for legs, trunk and arms (p < 0.001), but not for the head (p = 0.961). The locPASI for the head in younger female patients (18–40 years) had a higher score than those aged 55 + (p = 0.022) and after two years, middle aged (41–54) showed a lower score compared to younger patients (p = 0.045). Younger male patients revealed a lower score after two years of therapy in the leg- and arm-area compared to older (p = 0.018 and p = 0.048, respectively). Female patients on non-biologics had a fast initial response, converging with male patients’ scores over 24 months. Over 75% locPASI reduction was observed for female head-area (81.4%), male trunk (82.7%) and legs (76.1%). Absolute locPASI ≤ 2 was achieved 3–6 months for all locations with interleukin (IL)-17, IL-12/23 and IL-23-inhibitors, except for the legs of male patients on anti-IL-17 and female patients on anti-IL-12/23 and -IL-23. After two years, male patients did not achieve a locPASI ≤ 2 for any biologic-treatment in the legs, nor for the arms on anti-TNF-α. Significant disparities in localized PASI were observed between female and male patients. The age, sex and severity of distinct localizations should be considered to optimize treatment goals. [ABSTRACT FROM AUTHOR]

Epidemiological data demonstrate strong associations between psoriasis and metabolic comorbidities, including obesity, hypertension, diabetes mellitus, dyslipidemia, and non-alcoholic fatty liver disease. The presence of metabolic comorbidities significantly influences the selection and effectiveness of pharmacological treatments. Some drugs should be prescribed with caution in patients with metabolic comorbidities because of an increased risk of adverse events, while others could have a reduced effectiveness. The aim of this narrative review is to highlight the challenges that healthcare professionals may face regarding the management of psoriasis in patients with metabolic comorbidities. In the first part of the article, the epidemiological association between psoriasis and metabolic comorbidities and their pathogenetic mechanisms is summarized. The second part describes the efficacy and safety profile of conventional and biologic drugs in patients with selected metabolic comorbidities including obesity, non-alcoholic fatty liver disease/hepatic steatosis, and diabetes. Finally, the role of pharmacological and non-pharmacological interventions, such as diet, alcohol abstinence, physical activity, and smoking avoidance is discussed. In conclusion, the choice of the best approach to manage patients with psoriasis with metabolic comorbidities should encompass both tailored pharmacological and individualized non-pharmacological interventions. [ABSTRACT FROM AUTHOR]

Introduction: The introduction of biological therapies has revolutionized the treatment of moderate-to-severe plaque psoriasis. In particular, ixekizumab, an inhibitor of interleukin-17A, has shown great results in terms of efficacy and safety in both clinical trials and real-world experiences. However, there is a lack of long-term real-world data available for ixekizumab. Methods: We conducted a multicenter real-life study to evaluate the effectiveness and safety of ixekizumab in patients with moderate-to-severe plaque psoriasis. Psoriasis Area and Severity Index score (PASI) was collected at baseline and after 1, 2, 3, 4, and 5 years. The occurrence of any adverse events was recorded at each time point. Results: We enrolled 1096 patients treated with ixekizumab for at least 1 year. At week 52, the percentages of PASI 90 and PASI 100 were 85.04% and 69.07%, respectively. After 5 years of treatment with ixekizumab, out of 145 patients, a PASI 90 response was achieved by 86.90% of patients, while complete skin clearance was reached by 68.28% of patients. We did not observe any new significant safety findings throughout the study period. Conclusion: This study supports the long-term effectiveness and safety of ixekizumab in a real-world setting. [ABSTRACT FROM AUTHOR]

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Generalized pustular psoriasis (GPP) is a rare but severe skin inflammatory disorder characterized by the eruption of widespread sterile neutrophilic pustules, often accompanied by systemic inflammation. Given its life-threatening potential, GPP requires prompt accurate diagnosis and effective treatment, but its rarity and relapsing-remitting nature pose challenges in performing large-scale randomized controlled clinical trials. Established international guidelines are currently lacking and management guidance often follows that for plaque psoriasis. However, while it can co-exist with plaque psoriasis and has traditionally been classified as a most severe form of psoriasis, GPP is now recognized as a distinct entity, with its own clinicopathological, autoinflammatory, immunologic and genetic features. Research conducted over the past decade revealed that an imbalance of interleukin (IL)-36 signaling favoring the proinflammatory activity is the central driver of the pathogenesis of GPP, thereby laying the groundwork for the development of targeted therapies for the disease. This article reviews the evidence thus far on spesolimab, a selective humanized antibody against the IL-36 receptor that was recently licensed in Europe and the United States for the treatment of GPP flares in adults. In phase II, randomized controlled clinical trials, spesolimab led to rapid and effective skin clearance in patients experiencing a GPP flare and demonstrated superiority to placebo in preventing flares for up to 48 weeks with maintenance treatment, with reassuring safety and tolerability profiles. Spesolimab is considered to be a first-in-class medication establishing itself as the standard of care for the treatment of GPP flares, thus changing the paradigm of the management of GPP to a new era of scientifically- and evidence-based targeted therapy for this distinctive disease. [ABSTRACT FROM AUTHOR]

Psoriasis is a lifelong immune-driven skin condition characterized by excessive epidermal overgrowth and inflammatory cell infiltration. Gemifloxacin is a fourth-generation fluoroquinolone with improved immunomodulatory and anti-inflammatory properties that are believed to possess an attractive role in psoriasis via suppressing the production of cytokines, chemokines, and eosinophil and neutrophil chemotaxis. The aim of this research is to investigate the ameliorative effects of prolonged topical gemifloxacin (GMF) alone and combined with clobetasol propionate (CLO) on an imiquimod (IMQ)-induced mouse model of psoriasis. Forty-eight Swiss albino mice were divided into six groups of eight. All groups except the negative controls got 62.5 mg of IMQ 5% topically for 8 days. Mice in the control group (controls) got Vaseline instead. Following the induction in the IMQ 5% group, mice in treatment groups CLO 0.05, GMF 1%, GMF 3%, and CLO + GMF obtained clobetasol propionate 0.05%, GMF 1% and 3%, and a combination of both, respectively, for an additional 8 days, rendering the experiment 16 days long. Our results revealed that gemifloxacin alleviated erythematous, thickened, and scaly psoriatic lesions and inhibited the tissue level of inflammatory cytokines, including interleukin (IL)-8, IL-17A, IL-23, tumor necrosis factor-α (TNF-α), and transforming growth factor-β1 (TGF-β1). The anti-inflammatory effect also occurred by hindering nuclear factor-kappa B (NF-κB) signaling and reversing histopathological problems. Gemifloxacin acts effectively in mitigating psoriasis-associated lesions and restricting NF-κB-mediated inflammation, recommending gemifloxacin as a promising adjuvant candidate for additional studies on the long-term treatment of autoimmune and autoinflammatory dermatoses like psoriasis. [ABSTRACT FROM AUTHOR]

Axial symptoms (i.e., back pain) are common in the general population. At the same time 25–70% of patients with psoriatic arthritis (PsA) exhibit signs of inflammatory axial involvement (axial PsA). The presence of unexplained chronic (duration ≥ 3 months) back pain in a patient with psoriasis or PsA should trigger evaluation of the presence of axial involvement. Evaluation of axial involvement normally involves imaging of the axial skeleton (sacroiliac joints and/or spine) in addition to clinical and laboratory evaluation. Symptomatic patients with confirmed axial PsA are treated with a combination of non-pharmacologic and pharmacologic methods including the use of non-steroidal anti-inflammatory drugs, tumour necrosis factor, interleukin 17, and Janus kinase inhibitors. Interleukin 23 blockade might also be effective in the axial domain of PsA; a dedicated clinical study is ongoing at present. Safety considerations, patient preference, as well as the presence of other disease manifestations (especially of extra-musculoskeletal manifestations—clinically relevant psoriasis, acute anterior uveitis, inflammatory bowel disease), define the choice of a specific drug or drug class. [ABSTRACT FROM AUTHOR]

Objective: To examine data from studies supporting the clinical efficacy of medical approaches from India traditional systems of medicines like Ayurveda, Unani, Siddha, and Homeopathy for psoriasis using outcome indicators employed in clinical practice and research. Methods: Searches were conducted between December 2019 and September 2020 in databases PubMed, Scopus, Web of Science and Ovid Medline using search terms including traditional, complementary, psoriasis, Kushtha, Ayurveda, Siddha, Unani, Homeopathy and clinical. Controlled trials, case series and case reports published from India were included. Results: Data of 17 selected studies were extracted. Treatment efficacy in terms of improvement in Psoriasis Area and Severity Index (PASI) score or/and percentage reduction in score (PASI 50, PASI 75 and PASI 90) or/and patient-reported outcomes using instruments like Dermatology Life Quality Index and Psoriasis Disability Index were noted. All studies reported good improvement as per the study specific outcome. However, study characteristics, including study design, sample size, follow-up period, inclusion and exclusion criteria were heterogeneous, and the choice of outcome measures was not adequate to conclude the effectiveness of intervention. The use of some herbs as common ingredients in several formulations across different systems of medicines were noted in analyzing individual formulation. Conclusions: Future studies must incorporate a comprehensive study design with specific outcome measures like PASI, PASI 75, PASI 90, quality of life parameters, compliance to medications, adverse reactions, remission period, relapse rate and cost-effectiveness with long term follow-up. The currently available evidence on the roles of these herbs at molecular level in psoriasis is preliminary. [ABSTRACT FROM AUTHOR]

Background: Drug survival, defined as the length of time from initiation to discontinuation of a given therapy, allows comparisons between drugs, helps to predict patient's likelihood of remaining on a specific treatment, and achieving the best decision for each patient in daily clinical practice. Objective: The aim of this study was to provide data on drug survival of secukinumab, ixekizumab, brodalumab, guselkumab, tildrakizumab, and risankizumab in a large international cohort, and to identify clinical predictors that might have an impact on the drug survival of these drugs. Methods: This was a retrospective, multicentric, multi-country study that provides data of adult patients with moderate to severe psoriasis who started treatment with an interleukin (IL)-17 or IL-23 inhibitor between 1 February 2015 and 31 October 2021. Data were collected from 19 distinct hospital and non-hospital-based dermatology centers from Canada, Czech Republic, Italy, Greece, Portugal, Spain, and Switzerland. Kaplan–Meier estimator and proportional hazard Cox regression models were used for drug survival analysis. Results: A total of 4866 treatment courses (4178 patients)—overall time of exposure of 9500 patient-years—were included in this study, with 3164 corresponding to an IL-17 inhibitor (secukinumab, ixekizumab, brodalumab) and 1702 corresponding to an IL-23 inhibitor (guselkumab, risankizumab, tildrakizumab). IL-23 inhibitors had the highest drug survival rates during the entire study period. After 24 months of treatment, the cumulative probabilities of drug survival were 0.92 (95% confidence interval [CI] 0.89–0.95) for risankizumab, 0.90 (95% CI 0.88–0.92) for guselkumab, 0.80 (95% CI 0.76–0.84) for brodalumab, 0.79 (95% CI 0.76–0.82) for ixekizumab, and 0.75 (95% CI 0.73–0.77) for secukinumab. At 36 months, only guselkumab [0.88 (95% CI 0.85–0.91)], ixekizumab [0.73 (95% CI 0.70–0.76)], and secukinumab [0.67 (95% CI 0.65–0.70)] had more than 40 patients at risk of drug discontinuation. Only two drugs had more than 40 patients at risk of drug discontinuation at 48 months, with ixekizumab demonstrating to have a higher cumulative probability of drug survival [0.71 (95% CI 0.68–0.75)] when compared with secukinumab [0.63 (95% CI 0.60–0.66)]. Secondary failure was the main cause for drug discontinuation. According to the final multivariable model, patients receiving risankizumab, guselkumab, and ixekizumab were significantly less likely to discontinue treatment than those receiving secukinumab. Previous exposure to biologic agents, absent family history of psoriasis, higher baseline body mass index (BMI), and higher baseline Psoriasis Area and Severity Index (PASI) were identified as predictors of drug discontinuation. Conclusion: The cumulative probability of drug survival of both IL-17 and IL-23 inhibitors was higher than 75% at 24 months, with risankizumab and guselkumab demonstrating to have overall cumulative probabilities ≥ 90%. Biological agent chosen, prior exposure to biologic agents, higher baseline BMI and PASI values, and absence of family history of psoriasis were identified as predictors for drug discontinuation. Risankizumab, guselkumab, and ixekizumab were less likely to be discontinued than secukinumab. [ABSTRACT FROM AUTHOR]

Background: Psoriasis is a chronic inflammatory disorder of the skin; the hallmark of psoriasis is sustained inflammation that leads to uncontrolled keratinocyte proliferation and dysfunctional differentiation. Psoriasis shows clear autoimmune-related pathomechanisms, in which autoantigen-specific T cells contribute to the development, chronification, and overall course of the disease. Psoriasis is primarily a skin disease, but other internal organs may be involved; affliction of the joints is well established, but kidney involvement is yet to be universally agreed upon, although some recent studies have linked psoriasis to kidney disease and certain glomerular diseases including secondary renal amyloidosis, Ig A nephropathy, and membranous glomerulopathy. Case presentation and conclusion: In this paper, we report a case of primary membranoproliferative glomerulonephritis (MPGN) with nephrotic impure syndrome in a psoriatic patient. The etiological investigation was negative with normal serum complement and ASO titers and were negative for HBV, HCV, HIV, and ANA. The patient improved on prednisolone and angiotensin-converting enzyme inhibitors. To our best of knowledge, cases of MPGN associated with psoriasis are rare and we would like to shed light on this association. [ABSTRACT FROM AUTHOR]

Objective: To explore the efficacy and safety of Zhuang medicine medicated thread moxibustion (ZMTM) on psoriasis vulgaris. Methods: A multicenter, randomized, parallel controlled clinical trial was designed. A total of 241 outpatients with psoriasis vulgaris were randomly divided into a control group (120 cases) and a treatment group (121 cases) using a central block randomization from June 2015 to May 2018. The control group was treated with Western medicines alone including pidotimod dispersible tablets, vitamin B compound tablets, and compound cod liver oil-zinc oxide ointment. The treatment group was treated with ZMTM every 2 days combined with Western medicines. The two groups received continuous intervention for 30 days. The primary outcome was Psoriasis Area and Severity Index (PASI), and the secondary outcomes included Itch Rating Scale, Dermatology Quality of Life Index (DLQI), Hamilton Anxiety Rating Scale (HAMA), as well as PASI response rate. Meanwhile, adverse events were evaluated during the whole clinical trial. Follow-up was carried out 30 days after treatment. Results: There were 5 cases of shedding in this trial. In intention-to-treat analysis, 236 cases were included and each group contained 118 cases. On the 30th and 60th days, PASI scores of patients in each group were significantly lower than that at baseline (P<0.01) and the PASI score reduction of the treatment group was greater than that of the control group (P<0.01). Itch Rating Scale, DLQI, and HAMA scale were decreased in both groups after treatment, and the treatment group showed a better therapeutic effect (P<0.01). The response rates of PASI 50 and 75 were significantly higher than those in the control group [81.4% (96/118), 43.2% (51/118) vs. 41.5% (49/118), 11.0% (13/118), respectively, P<0.05]. During follow-up, the improvements in scores of PASI, Itch Rating Scale, DLQI, and HAMA of the treatment group were significantly greater than those of the control group (P<0.01). The response rates of PASI 50 and 75 in the treatment group were significantly higher than those in the control group, respectively (both P<0.05). No obvious adverse reaction was found in either group. Conclusion: ZMTM combined with Western medicines showed a better therapeutic effect in the treatment of psoriasis vulgaris without obvious adverse reaction. (Trial Registration No. ChiCTR-IOR-16008159) [ABSTRACT FROM AUTHOR]

Generalized pustular psoriasis (GPP) is a rare neutrophilic skin condition characterized by episodes of widespread eruption of sterile macroscopic pustules that can be associated with systemic inflammation. The rarity of GPP and its heterogeneous cutaneous and extracutaneous symptoms pose considerable challenges to the development and adoption of comprehensive accurate disease measures for the routine clinical assessment of disease severity and the evaluation of new treatments in clinical trials. Psoriasis disease measures remain among the most commonly used methods for evaluating patients with GPP, despite their limitations owing to a lack of assessment of pustules (a hallmark of GPP), systemic inflammation, and disease symptoms. The adaptation of psoriasis disease measures and the development of assessment tools specific for GPP severity will enable more effective and accurate monitoring of patients with GPP and enhance the clinical development of new therapies. Further clinical validation of recently developed modified assessment tools, such as the Generalized Pustular Psoriasis Physician Global Assessment and the Generalized Pustular Psoriasis Area and Severity Index, and international consensus on using quantitative tools and patient-reported outcome measures in the development of new treatments are needed to advance patient care. [ABSTRACT FROM AUTHOR]

Purpose Of Review: Psoriasis and psoriatic arthropathy are inflammatory autoimmune conditions that can lead to profound emotional distress, social stigmatization, isolation, disfigurement, pain, disability, unemployment, and decreased quality of life. Thus, this disease has immense psychological, social, and economic implications as the pain experienced is closely associated with the primary disease burden. This review focuses on discussing the primary disease burden of psoriasis and psoriatic arthropathy, as well as management of different types of pain in these patients.Recent Findings: Pain affects over 40% of patients with psoriasis, ranging from neuropathic to nociceptive. Treatment of pain largely focuses on treating the underlying disease with mild topical steroids and non-steroidal medications including vitamin D analogs followed by systemic immunomodulatory agents for more severe disease. Interventional options such as corticosteroid injections are available for select cases (conditional recommendation). Psoriasis and psoriatic arthropathy have been associated with underreporting and resultant undertreatment of pain. Pain control in these conditions is complex and requires a multidisciplinary approach. More research and guidelines are needed in the areas of reporting of psoriatic disease, associated pain, psoriatic nociception, and optimal clinical management. [ABSTRACT FROM AUTHOR]

The nuclear receptor retinoid-related orphan receptor gamma t (RORγt) plays a critical role in driving Th17 cell differentiation and expansion, as well as IL-17 production in innate and adaptive immune cells. The IL-23/IL-17 axis is implicated in several autoimmune and inflammatory diseases, and biologics targeting IL-23 and IL-17 have shown significant clinical efficacy in treating psoriasis and psoriatic arthritis. JNJ-61803534 is a potent RORγt inverse agonist, selectively inhibiting RORγt-driven transcription versus closely-related family members, RORα and RORβ. JNJ-61803534 inhibited IL-17A production in human CD4+ T cells under Th17 differentiation conditions, but did not inhibit IFNγ production under Th1 differentiation conditions, and had no impact on in vitro differentiation of regulatory T cells (Treg), nor on the suppressive activity of natural Tregs. In the mouse collagen-induced arthritis model, JNJ-61803534 dose-dependently attenuated inflammation, achieving ~ 90% maximum inhibition of clinical score. JNJ-61803534 significantly inhibited disease score in the imiquimod-induced mouse skin inflammation model, and dose-dependently inhibited the expression of RORγt-regulated genes, including IL-17A, IL-17F, IL-22 and IL-23R. Preclinical 1-month toxicity studies in rats and dogs identified doses that were well tolerated supporting progression into first-in-human studies. An oral formulation of JNJ-61803534 was studied in a phase 1 randomized double-blind study in healthy human volunteers to assess safety, pharmacokinetics, and pharmacodynamics. The compound was well tolerated in single ascending doses (SAD) up to 200 mg, and exhibited dose-dependent increases in exposure upon oral dosing, with a plasma half-life of 164 to 170 h. In addition, dose-dependent inhibition of ex vivo stimulated IL-17A production in whole blood was observed, demonstrating in vivo target engagement. In conclusion, JNJ-61803534 is a potent and selective RORγt inhibitor that exhibited acceptable preclinical safety and efficacy, as well as an acceptable safety profile in a healthy volunteer SAD study, with clear evidence of a pharmacodynamic effect in humans. [ABSTRACT FROM AUTHOR]

Psoriasis is a chronic inflammatory skin condition with regional and ethnic differences in its prevalence and clinical manifestations. Human leukocyte antigen (HLA)-Cw6 is the disease allele conferring the greatest risk to psoriasis, but its prevalence is lower in Asian individuals. Recent studies have found associations between HLA-Cw1 and some Asian populations with psoriasis, especially Southern Chinese. HLA-Cw6 was associated with type I early-onset psoriasis, guttate psoriasis, Koebner phenomenon, and better response to methotrexate, interleukin (IL)-12/23, IL-17, and IL-23 targeting drugs. In contrast, HLA-Cw1 positivity has been associated with erythrodermic psoriasis, pustular psoriasis, and the axial type of psoriatic arthritis. Furthermore, HLA-Cw1 was more frequently associated with high-need patients who did not respond to conventional therapies. No known trigger factor nor autoantigen has been identified for HLA-Cw1 positivity. However, HLA-Cw1 has been linked to some viral agents. For example, cytotoxic T lymphocytes recognize multiple cytomegalovirus pp65-derived epitopes presented by HLA alleles, including HLA-C*01:02. In addition, cytomegalovirus can lead to severe exacerbation of psoriatic skin disease. The proposed interaction between viral infection, HLA-Cw1, and psoriasis is through the killer cell immunoglobulin-like receptors of natural killer cells. Given the diverse nature of psoriasis pathogenesis and the difference in HLA-Cw prevalence in different racial groups, more studies are needed to confirm the role of HLA-Cw1 in psoriasis. [ABSTRACT FROM AUTHOR]

The concept of psoriatic arthritis (PsA) prevention is gaining increased interest owing to the physical limitation, poor quality of life and low remission rates that are achieved with current therapies for PsA. The psoriasis-to-PsA transition offers a unique opportunity to identify individuals at increased risk of developing PsA and to implement preventive strategies. However, identifying individuals at increased risk of developing PsA is challenging as there is no consensus on how this population should be defined. This Consensus Statement puts forward recommended terminology from the Psoriasis and Psoriatic Arthritis Clinics Multicenter Advancement Network (PPACMAN) for defining specific subgroups of individuals during the preclinical and early clinical phases of PsA to be used in research studies. Following a three-round Delphi process, consensus was reached for three terms and definitions: 'increased risk for PsA', 'psoriasis with asymptomatic synovio-entheseal imaging abnormalities' and 'psoriasis with musculoskeletal symptoms not explained by other diagnosis'. These terms and their definitions will enable improved identification and standardization of study populations in clinical research. In the future, as increasing evidence emerges regarding the molecular and clinical features of the psoriasis-to-PsA continuum, these terms and definitions will be further refined and updated. [ABSTRACT FROM AUTHOR]

Anti-drug antibodies (ADAs) may develop against originator biologic and biosimilar therapies used for the treatment of psoriasis and may be the cause of initial therapeutic non-response or diminished therapeutic response over time. Comparing immunogenicity between therapeutic agents is challenging owing to the variation in assays used for detection, among other reasons. Using the results of a PubMed search for psoriasis clinical trials disclosing the rates of ADAs for originator biologic and biosimilar therapies approved for the treatment of psoriasis within the last 5 years, this review discusses the rates and potential clinical impact of ADA formation in patients with psoriasis managed with originator biologic and biosimilar therapies, along with novel methods of ADA testing. Anti-drug antibodies are detectable in all biologic and biosimilar therapies approved for the treatment of psoriasis in the last 5 years, and the effect of ADAs on clinical response varies by agent. Novel immunoassays used for the detection of ADAs may have increased sensitivity compared with traditional assays, although the increased rate of detection may not correlate with decreased clinical response and the decision to test for the presence of ADAs may vary from patient to patient. Though ADA formation seems ubiquitous with the use of biologic agents for the treatment of psoriasis, the increased rates of ADAs detected by novel immunoassays may not necessarily correlate with decreased treatment efficacy. [ABSTRACT FROM AUTHOR]

Chondroitin sulfates are implicated in epidermal biology, but functional significance of chondroitin sulfates remains unclear. Here, we report that chondroitin 6-sulfate is important for the maintenance of epidermal homeostasis. Mice deficient in chondroitin 6-O-sulfotransferase-1 (C6st-1), which is involved in biosynthesis of chondroitin 6-sulfate, exhibited keratinocyte hyperproliferation and impaired skin permeability barrier function. Chondroitin 6-sulfate directly interacted with the EGF receptor and negatively controlled ligand-induced EGF receptor signaling. Normal function of hyperproliferative C6st-1-knockout mouse-derived keratinocytes was rescued by treatment with exogenous chondroitin 6-sulfate. Epidermal hyperplasia, induced using imiquimod, was more severe in C6st-1-knockout mice than in C6st-1 wild-type mice. Taken together, these findings indicate that chondroitin 6-sulfate represses keratinocyte proliferation in normal skin, and that the expression level of C6st-1 may be associated with susceptibility to psoriasis. Kitazawa et al. show that chondroitin 6-sulfate represses keratinocyte proliferation in skin. They find that mice deficient in chondroitin-6-O-sulfotransferase-1 (C6st-1), which synthesizes chondroitin 6-sulfate, exhibit keratinocyte hyperproliferation and impaired skin permeability barrier. This study suggests that the expression level of C6st-1 may serve as a biomarker for the susceptibility to psoriasis. [ABSTRACT FROM AUTHOR]

Psoriasis is a chronic inflammatory skin disease clinically characterized by the appearance of red colored, well-demarcated plaques with thickened skin and with silvery scales. Recent studies have established the involvement of a complex signalling network of interactions between cytokines, immune cells and skin cells called keratinocytes. Keratinocytes form the cells of the outermost layer of the skin (epidermis). Visible plaques in psoriasis are developed due to the fast proliferation and unusual differentiation of keratinocyte cells. Despite that, the exact mechanism of the appearance of these plaques in the cytokine-immune cell network is not clear. A mathematical model embodying interactions between key immune cells believed to be involved in psoriasis, keratinocytes and relevant cytokines has been developed. The complex network formed of these interactions poses several challenges. Here, we choose to study subnetworks of this complex network and initially focus on interactions involving TNF α , IL-23/IL-17, and IL-15. These are chosen based on known evidence of their therapeutic efficacy. In addition, we explore the role of IL-15 in the pathogenesis of psoriasis and its potential as a future drug target for a novel treatment option. We perform steady state analyses for these subnetworks and demonstrate that the interactions between cells, driven by cytokines could cause the emergence of a psoriasis state (hyper-proliferation of keratinocytes) when levels of TNF α , IL-23/IL-17 or IL-15 are increased. The model results explain and support the clinical potentiality of anti-cytokine treatments. Interestingly, our results suggest different dynamic scenarios underpin the pathogenesis of psoriasis, depending upon the dominant cytokines of subnetworks. We observed that the increase in the level of IL-23/IL-17 and IL-15 could lead to psoriasis via a bistable route, whereas an increase in the level of TNF α would lead to a monotonic and gradual disease progression. Further, we demonstrate how this insight, bistability, could be exploited to improve the current therapies and develop novel treatment strategies for psoriasis. [ABSTRACT FROM AUTHOR]

Psoriatic disease (PsD) is a heterogeneous condition that can affect peripheral and axial joints (arthritis), entheses, skin (psoriasis) and other structures. Over the past decade, considerable advances have been made both in our understanding of the pathogenesis of PsD and in the treatment of its diverse manifestations. However, several major areas of continued unmet need in the care of patients with PsD have been identified. One of these areas is the prediction of poor outcome, notably radiographic outcome in patients with psoriatic arthritis, so that stratified medicine approaches can be taken; another is predicting response to the numerous current and emerging therapies for PsD, so that precision medicine can be applied to rapidly improve clinical outcome and reduce the risk of toxicity. In order to address these needs, novel approaches, including imaging, tissue analysis and the application of proteogenomic technologies, are proposed as methodological solutions that will assist the dissection of the critical immune-metabolic pathways in this complex disease. Learning from advances made in other inflammatory diseases, it is time to address these unmet needs in a multi-centre partnership aimed at improving short-term and long-term outcomes for patients with PsD. [ABSTRACT FROM AUTHOR]

Stratified medicine is the tailoring of treatment to the individual characteristics of each patient. This is a challenging task in the context of psoriasis, a complex disease with a variety of phenotypic presentations and a comorbidity burden that extends beyond cutaneous manifestations. In recent years, considerable progress has been made in understanding the immunology of psoriasis, and this has informed the development of increasingly precise and efficacious therapies. However, not all patients respond to biologic therapy, and access is limited to patients with moderate to severe disease. However, subpopulations of patients are emerging with distinct patterns of response to therapy, largely determined by clinical and pharmacogenomic factors. Despite progress to date, the natural history of psoriasis remains poorly understood. It is likely that disease onset, progression, development of comorbidities and response to therapy are due to a combination of genetic, inflammatory and environmental factors. We envision that a greater understanding of the natural history of psoriasis will be a key factor in progressing a stratified medicine approach to patient care, as will earlier intervention in the course of the disease. [ABSTRACT FROM AUTHOR]

Psoriasis is a chronic immune-mediated inflammatory disease that predominantly affects the skin and joints. Its detrimental effects on the physical, psychosocial, and emotional well-being of patients leads to a significant reduction in quality of life (QoL). The goals of treatment focus on decreasing disease severity and improving QoL for patients; accomplishing these goals requires physicians to understand both the full impact of the disease on a patient's life and the outcomes that matter most to patients. The use of outcome measures, both physician- and patient-reported, can assist clinicians in evaluating the disease burden and its effect on QoL and in identifying patient preferences for treatment, ultimately enhancing quality of care. However, current outcome measures have many limitations and do not adequately capture patients' needs and priorities. Nevertheless, physicians treating patients with psoriasis are encouraged to utilize these instruments while remaining cognizant of each of their limitations. As there is no consensus on an outcome measure that fully encompasses the complexities of psoriasis and its impact on patients, instruments that are appropriate and applicable to dermatologists and their patients should be developed. [ABSTRACT FROM AUTHOR]

Although the pathogenesis of Alzheimer's disease (AD) is unclear, neuroinflammation appears to play a role in its development. Psoriasis is a chronic inflammatory skin disease that has recently been found to genetically overlap with AD. We aimed to investigate the risk of AD in patients with psoriasis. Subjects with psoriasis (n = 535,927) and age- and sex-matched controls without psoriasis (at a 5:1 ratio; n = 2,679,635) who underwent ≥3 health examinations between 2008 and 2014 were included, drawn from the Korean National Health Insurance System database. There were 50,209 cases of AD (1.87%) in controls without psoriasis and 11,311 cases (2.11%) in patients with psoriasis, and the median follow-up was 3.35 years. In a multivariable-adjusted model, patients with psoriasis showed a significantly increased risk of AD (hazard ratio, 1.09; 95% CI, 1.07–1.12, p < 0.0001) compared to controls without psoriasis. Among patients with psoriasis, the risk of AD was significantly increased in psoriasis patients not receiving systemic therapy compared to those receiving systemic therapy (hazard ratio, 1.10; 95% CI, 1.08–1.12 vs. hazard ratio, 0.99; 95% CI: 0.90–1.09, p < 0.0001). The incidence of AD was significantly increased in patients with psoriasis compared to control subjects without psoriasis. Of note, systemic treatment for psoriasis was associated with a reduced risk of AD. [ABSTRACT FROM AUTHOR]

Drug screening studies for inflammatory skin diseases are currently performed using model systems that only partially recapitulate human diseased skin. Here, we developed a new strategy to incorporate T cells into human 3D skin constructs (HSCs), which enabled us to closely monitor and quantitate T cell responses. We found that the epidermis promotes the activation and infiltration of T cells into the skin, and provides a directional cue for their selective migration towards the epidermis. We established a psoriatic HSC (pHSC) by incorporating polarized Th1/Th17 cells or CCR6+CLA+ T cells derived from psoriasis patients into the constructs. These pHSCs showed a psoriatic epidermal phenotype and characteristic cytokine profiles, and responded to various classes of psoriasis drugs, highlighting the potential utility of our model as a drug screening platform. Taken together, we developed an advanced immunocompetent 3D skin model to investigate epidermal-T cell interactions and to understand the pathophysiology of inflammatory skin diseases in a human-relevant and patient-specific context. [ABSTRACT FROM AUTHOR]

Elderly patients are a group with a high frequency of psoriasis. Their disease burden has negative impacts on their quality of life. While there is a clear need to treat these patients, there are challenges in doing so. This work seeks to define the challenges that exist in treating elderly Medicare patients, as well as to provide treatment suggestions for providers to follow if they encounter one or more of these challenges. Providers face the following challenges when creating treatment plants for elderly patients with psoriasis: difficulty in obtaining drug coverage through Medicare, increased medical comorbidities, and polypharmacy. Providers aim for regimens that are affordable, safe, and efficacious, but it is not always clear how to achieve this combination, especially in elderly Medicare patients. This work is relevant in that it aims to explain the logistical roadblocks posed by Medicare coverage and provide solutions for commonly encountered issues in the treatment of a disabling and common disease in a high-risk population. Specifically, alternative treatment options to biologics and small-molecule inhibitors are discussed and include topical therapies, phototherapy, methotrexate, acitretin, and cyclosporine and for psoriatic arthritis include corticosteroids and leflunomide. The specific risks and benefits of these therapies in the elderly population are provided, allowing providers to make patient-specific decisions about optimal regimens. [ABSTRACT FROM AUTHOR]

Psoriasis involving the genital skin occurs in up to two-thirds of psoriasis patients but is often overlooked by physicians. Furthermore, psoriasis objective and subjective severity indexes for common plaque psoriasis often neglect the impact this small area of psoriasis can have on a patient. It can have a significant impact on patients' psychosocial function due to intrusive physical symptoms such as genital itch and pain, and a detrimental impact on sexual health and impaired relationships. The mainstay of treatment is topical therapy. In patients with genital psoriasis refractory to traditional topical treatment, biologic treatments may greatly improve patient outcomes. [ABSTRACT FROM AUTHOR]

With the extensive variety of available treatments for psoriasis, it is paramount that clinicians understand the differences between therapies. A critical literature gap exists regarding the effects of different systemic therapies on physical and mental functioning in the US psoriasis population. We sought to compare the impact of biologic versus oral therapy on measures of physical and mental functioning among US adults with moderate-to-severe psoriasis. We performed a nationwide, cross-sectional study of 2,431,282 (weighted) (183 non-weighted) US adults with psoriasis on biologic or oral therapy using the 2003–2015 Medical Expenditure Panel Survey (MEPS). Physical and mental functioning were measured with the Short Form-12 version 2 (SF-12v2) Physical Component Summary (PCS) and Mental Component Summary (MCS), respectively. The mean PCS score among patients on biologic therapy was significantly higher than that of patients on oral therapy (46.25 [95% CI 43.91–48.59] versus 42.39 [95% CI 41.05–43.73]; P < 0.01). The mean MCS score among patients on biologic therapy was also significantly higher than that of patients on oral therapy (52.46 [95% CI 50.51–54.41] versus 50.19 [95% CI 49.00–51.38]; P < 0.05). Based on adjusted multiple linear regression, biologic therapy was associated with a significantly greater increase in measures of physical functioning (P < 0.05) and mental functioning (P < 0.001) as compared to oral therapy. In conclusion, clinicians need to account for physical and mental health when making treatment decisions. Biologic therapy is associated with significantly greater increases in measures of physical and mental functioning when compared to oral therapy in the US adult psoriasis population. [ABSTRACT FROM AUTHOR]

Fatty acid-binding proteins play an inconclusive role in lipid metabolism and cardiometabolic diseases (CMDs) which are closely related with psoriasis. Aim of the study was to investigate the diagnostic value of serum liver fatty acid-binding protein (FABP1) level and associations with disease severity, inflammation or metabolic parameters and influence of systemic treatment in psoriatic patients. The study included thirty-three patients with active plaque-type psoriasis and eleven healthy volunteers. Blood samples were obtained before and after 12 weeks of therapy with methotrexate and acitretin. Serum FABP1 concentrations were analyzed by the enzyme-linked immunosorbent assay. Statistical analysis was performed for correlation of FABP1 with anthropometric, metabolic or inflammatory indices and treatment used. Serum liver-type FABP levels were significantly increased in psoriatic patients compared to the controls (p < 0.001). No statistical correlations between FABP1 and PASI (p = 0.25) was noted, however patients with severe psoriasis had the highest level of FABP1. No significance with metabolic parameters was obtained, beside a positive significant relation with BMI after therapy (p = 0.03). Liver-type FABP significantly correlated with CRP (p = 0.01) and morphotic blood elements. Systemic treatment combined resulted in significant decrease of FABP1 (p = 0.04), regardless of the drug: p = 0.1 in acitretin group, p = 0.3 in methotrexate group. Liver-type FABP might be a novel marker of psoriasis and predictor of clinical response to systemic therapy. FABP1 could be involved in CMDs risk assessment and perhaps link psoriasis with hematological disorders. [ABSTRACT FROM AUTHOR]

Introduction: We review the literature evaluating certolizumab in psoriasis and report our experience of treatment outcomes in a joint dermatology and rheumatology clinic. Methods: Patients with concomitant psoriatic arthritis (PsA) and psoriasis who had been commenced on certolizumab were included within our retrospective review. Data was collected for patient demographics, Patient Area and Severity Index (PASI), Dermatology Life Quality Index (DLQI) and previous treatments. The literature was systematically searched using Pubmed and Scopus. Results: Very recent results from the CIMPASI-1 and CIMPASI-2 studies have demonstrated the high efficacy of certolizumab in the treatment of psoriasis at both week 16 and 48. Pooled results from these studies showed a PASI75 at week 16 and week 48 of 82% and 83.6% respectively, in the certolizumab 400 mg group. In our cohort of eight patients (two female; six male; median age 49 and mean PASI of 20.8) all had failed at least two systemic non-biologic agents. Objective improvements were observed in seven patients, with five achieving PASI90 and two demonstrating either PASI75 or PASI50. Conclusion: Certolizumab is efficacious in both psoriasis and PsA, including in patients who are biologic failures, and could be considered as an alternative treatment modality. [ABSTRACT FROM AUTHOR]

Objective: To observe the clinical effectiveness and safety of fire-needle therapy, an external approach of Chinese medicine in treating plaque psoriasis. Methods: This study was a two-parallel-arm randomized controlled trial. A total of 151 participants with plaque psoriasis were randomly assigned to the fire-needle therapy group (treatment group, 76 cases) or the control group (75 cases) at a 1:1 allocation ratio using SAS software. All participants received Oral Huoxue Jiedu Decoction (活血解毒汤, HXJDD) and applied externally vaseline cream twice a day. Participants in the treatment group received fire-needle therapy once weekly for 4 weeks plus HXJDD and vaseline cream applied the same as the control group. The primary outcome measure was Psoriasis Area and Severity Index (PASI) score, and the secondary outcomes were Dermatology Life Quality Index (DLQL), and Hamilton Anxiety Rating Scale (HAMA), as well as Chinese medicine (CM) syndrome score and photos of target lesions. The indices were evaluated before and after treatment. Results: Sixty-eight patients in each group completed the study. The treatment group has not yet achieved significant improvement in PASI score (P>0.05) compared to the control group. However, significant differences were found between the two groups in relieving CM syndrome (P<0.05) and improving quality of life (P<0.05). Conclusion: Fire-needle appears to be safe and may have benefit for psoriasis, the short-term treatment and small sample size limit the conclusions of this study. Further rigorous randomized controlled trials with longer treatment are recommended. [ABSTRACT FROM AUTHOR]

Background: The relationship between psoriasis and vitiligo has not been previously confirmed, and we therefore aimed to investigate this association.Methods: We conducted a search of the MEDLINE and EMBASE electronic databases on 22 January 2018 for case-control, cross-sectional, and cohort studies examining the association between psoriasis and vitiligo. A customized Newcastle-Ottawa Scale was used to assess the risk of bias of the included studies. We performed a random effects meta-analysis to calculate pooled odds ratios (ORs) with 95% confidence intervals (CIs) for case-control and cross-sectional studies.Results: Of 2453 citations identified from the literature search, 10 case-control/cross-sectional studies with a total of 120,866 psoriasis cases and 79,907 vitiligo cases were included in our study. Four of these studies were rated as high risk of bias. We found a significantly increased odds for vitiligo in psoriasis patients (summary OR 2.29, 95% CI 1.56-3.37, studies = 7), as well as a significantly elevated odds for psoriasis in vitiligo patients (summary OR 3.43, 95% CI 1.86-6.33, studies = 4).Conclusions: Our meta-analysis showed that psoriasis and vitiligo are associated with each other. Several studies had a high risk of bias, and further investigation is needed to confirm this association and amplify treatment options. [ABSTRACT FROM AUTHOR]

Background: Patients with psoriasis face numerous treatment and self-management decisions. Shared decision making is a novel approach where patients' preferences and values are considered in cooperation with healthcare professionals before making treatment decisions.Objective: The objective of this systematic review was to explore what is illuminated in psoriasis research regarding shared decision making, and to estimate the effects of shared decision-making interventions in this context.Methods: Qualitative, quantitative, and mixed-methods studies were eligible for inclusion. We searched six electronic databases up to January 2018. Two reviewers independently applied inclusion and quality criteria. The SPIDER framework was used to identify eligibility criteria for study inclusion. Narrative and thematic syntheses were utilized to identify prominent themes emerging from the data.Results: A total of 23 studies were included in the review. Of these, we included 18 studies (19 papers) to describe what was illuminated with regard to shared decision making in psoriasis research. Four major themes emerged: interpersonal communication; exchange of competence and knowledge; different world view; and involvement and preference, organized under two analytical themes; "Co-creation of decisions" and "Organization of treatment and treatment needs". For shared decision-making effects, we included four controlled studies. These varied in scope and interventional length and showed limited use of shared decision making-specific outcome measures, reflecting the early stage of the literature. Because of study heterogeneity, a meta-synthesis was not justified.Conclusions: There appears to be a need to strengthen the relationship between medical doctors and patients with psoriasis. The evident lack of knowledge about each other's competence and the lack of self-efficacy for both patients and providers challenges the basic principles of shared decision making. The effects of shared decision making in psoriasis are inconclusive, and more research appears necessary to determine the possible benefits of shared decision-making interventions. [ABSTRACT FROM AUTHOR]

Background: This study aimed to explore the correlation of circulating inflammatory cytokines' levels with treatment response to etanercept (ETN) treatment in psoriasis patients. Methods: 97 moderate-to-severe plaque-psoriasis patients were continuously recruited in this prospective cohort study, and all patients received ETN treatment. Serum samples were collected before and at 6 months (M6) after treatment, and nine inflammatory cytokines expressions were detected by enzyme-linked immuno sorbent assay. Psoriasis Area and Severity Index (PASI) score was evaluated at baseline (M0), 1 month (M1), 3 months (M3) and M6 after treatment, and the corresponding PASI 75/90 responses' rates were calculated. Results: Tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1β, IL-6, IL-12, IL-17A, IL-22, IL-23, and IL-32 levels were reduced, while IL-10 level was elevated at M6 after ETN treatment compared to baseline. PASI 75/90 responses' rates to ETN were 69.1 and 38.1% at M6, respectively. IL-1β and IL-17A levels were elevated in PASI 75-response patients compared to PASI 75 non-response patients, while IL-17A level was also increased in PASI 90-response patients compared to PASI 90 non-response patients. Multivariate logistic regression revealed that IL-1β, IL-17A and combined phototherapy during study predicted higher, while previous systemic biologic treatment predicted lower PASI 75 response to ETN independently. In addition, IL-17A independently predicted higher PASI 90 response to ETN as well. Conclusions: IL-1β, IL-17A, and combined phototherapy predicts higher while previous systemic biologic treatment predicts lower treatment response to ETN independently in psoriasis patients. [ABSTRACT FROM AUTHOR]

As part of the National Institute for Health and Care Excellence single technology appraisal process, brodalumab was assessed to determine the clinical and cost effectiveness of its use in the treatment of moderate-to-severe plaque psoriasis. The Centre for Reviews and Dissemination and the Centre for Health Economics Technology Assessment Group at the University of York were commissioned to act as the independent Evidence Review Group. This article provides a summary of the Evidence Review Group's review of the company's submission, the Evidence Review Group report and the National Institute for Health and Care Excellence Appraisal Committee's subsequent guidance issued in March 2018. The main clinical effectiveness data were derived from three well-conducted, multicentre, double-blind randomised controlled trials. The trials demonstrated that brodalumab statistically significantly reduced the severity of psoriasis and its impact on health-related quality of life, compared with placebo, at 12 weeks. In comparison with ustekinumab, statistically significantly more patients taking brodalumab had reduced psoriasis severity at 12 weeks. Psoriasis severity and quality of life also appeared improved at 52 weeks, although statistical significance was not assessed. Withdrawal rates were comparable to drug survival rates of other biological therapies and rates of adverse events were similar between brodalumab and ustekinumab. A network meta-analysis was presented, comparing brodalumab with other therapies available at the same point in the treatment pathway (i.e. in patients for whom standard systemic therapy or phototherapy is inadequately effective, not tolerated or contraindicated). The network meta-analysis ranked treatments in order of effectiveness, in terms of achieving different levels of Psoriasis Area and Severity Index response. The results indicated that brodalumab had a similar probability of response to ixekizumab, secukinumab and infliximab and a higher probability of response than ustekinumab, adalimumab, etanercept, apremilast, dimethyl fumarate and placebo. The company's economic model compared nine treatment sequences that included three lines of active therapy, consisting of brodalumab and other comparators recommended by the National Institute for Health and Care Excellence, followed by best supportive care. The sequence with brodalumab in the first-line position dominated sequences that started with adalimumab, infliximab, secukinumab and ustekinumab. The incremental cost-effectiveness ratio of the brodalumab sequence compared to less effective and non-dominated sequences ranged from £7145 (vs. the etanercept sequence) to £13,353 (vs. the dimethyl fumarate sequence) per quality-adjusted life-year gained. The incremental cost-effectiveness ratio for the more costly and effective ixekizumab sequence was £894,010 per quality-adjusted life-year gained compared to the brodalumab sequence. At a threshold of £20,000 per quality-adjusted life-year gained, the brodalumab sequence had the highest probability of being cost effective (96%). The main limitation of the company's economic model was the restrictive nature of the sequences compared. Twelve separate scenarios based on key uncertainties were explored by the Evidence Review Group. The only scenarios where brodalumab was ranked lower than first were not considered to be more appropriate or plausible than the assumptions or scenarios included in the company's base case. The treatment rankings identified in the Evidence Review Group's alternative base case were identical to those derived from the company's base case model. At the first National Institute for Health and Care Excellence Appraisal Committee meeting, the Committee concluded that brodalumab appears to be as effective as other anti-interleukin-17 agents and is cost effective, based on the discount agreed in the patient access scheme. Brodalumab is recommended as an option for treating adults with severe plaque psoriasis (defined by a total Psoriasis Area and Severity Index score of 10 or more and a Dermatology Life Quality Index score of more than 10) who have not responded to other systemic non-biological therapies. Brodalumab should be stopped at 12 weeks if the psoriasis has not responded adequately. [ABSTRACT FROM AUTHOR]

Background: Nowadays, even though several biologic therapies are available to treat psoriasis, multidrug-resistant disease continues to be a therapeutic challenge. Combination therapy has therefore become increasingly important. In this context, apremilast, according to its safety profile, could easily be combined with biologics in patients with comorbidities and/or recalcitrant multidrug-resistant psoriasis.Objective: Our goal is to share experience from our institution in the observation of a patient with severe chronic plaque psoriasis that was unresponsive to all anti-tumor necrosis factor-α treatment and to an anti-interleukin (IL)-17A drug and only partially responsive to ustekinumab, even in combination with apremilast. The patient carried a rare allele infrequently found in Caucasian people: human leukocyte antigen (HLA)-C*18:01. This allele has been found to be positively associated with psoriasis in Brazilian patients.Methods: The patient was typed for the HLA-C locus at high resolution via polymerase chain reaction sequence-specific oligonucleotide probes (PCR-SSOP) using a commercial kit (LAB®Type, One Lambda Inc., Canoga Park, CA, USA).Results: Our patient, previously described as having multidrug-resistant psoriasis, commenced ustekinumab and apremilast combination therapy. After 12 weeks, the Psoriasis Area Severity Index score had worsened, and we suspended combination therapy because the patient reported an absence of any benefit and was experiencing side effects from the induction therapy with apremilast.Conclusions: Expanding on the previously reported experience with this patient, we conclude that HLA-C*18:01 probably indicates a severe, recalcitrant, multidrug-resistant psoriasis phenotype for which proper therapy remains to be identified. [ABSTRACT FROM AUTHOR]

Psoriasis is a chronic inflammatory disease affecting the skin, nails, and joints. About 61% of psoriatic patients have nail involvement that can cause a significant social problem. Treating nail psoriasis is challenging but can improve the health outcomes and quality of life of patients. Treatment options available for nail psoriasis including topical therapy, intralesional injections, and systemic and biologic agents have various side effects and some benefits. Management is currently inconclusive. Intralesional injection of methotrexate in nail psoriasis was previously documented in few cases. We present a case of nail psoriasis successfully treated with low-dose intralesional methotrexate with no significant side effects in a 48-year-old psoriatic patient. Given the various side effects of conventional topical and systemic therapies limiting their use, we conclude that intralesional methotrexate injection seems to be a safe and effective treatment option for nail psoriasis. However, large controlled studies are needed. [ABSTRACT FROM AUTHOR]

Introduction: We evaluated baseline itch and its impact on the efficacy of ixekizumab (IXE) in clearing psoriasis and improving quality-of-life measures, and we explored the relationship between itch and psoriatic skin improvement.Methods: Data were analyzed from two double-blind, randomized, controlled phase III studies (UNCOVER-2/3) comparing etanercept (ETN), IXE, and placebo (PBO) in patients with moderate-to-severe plaque psoriasis. Long-term analysis included UNCOVER-3 data from week 0 to week 156.Results: At week 12, a clinically meaningful improvement in itch [Itch Numeric Rating Scale (NRS) reduction ≥ 4] was seen in 70.0%, 88.6%, and 90.8% of the IXE-treated patients in the baseline Itch NRS 4-6, 7-8, and 9-10 groups, respectively (all itch severity groups p < 0.001 versus ETN and PBO). Also, 68.9%, 67.1%, and 73.6% of the IXE-treated patients in the baseline Itch NRS 4-6, 7-8, and 9-10 groups, respectively, showed an improvement of ≥ 90.0% in the Psoriatic Area and Severity Index (PASI) at week 12 as compared to the baseline (PASI 90) (all itch severity groups p < 0.001 versus ETN and PBO). For most patients, itch reduction preceded psoriatic plaque improvement. Sustained effects of IXE on itch and PASI were observed during 3 years of treatment.Conclusions: Regardless of baseline itch severity, IXE treatment provided a rapid improvement in itch followed by clinically meaningful improvements in psoriasis.Funding: Eli Lilly and Company.Trial registration: ClinicalTrials.gov identifiers, NCT01597245 and NCT01646177. [ABSTRACT FROM AUTHOR]

Introduction: Secukinumab, a fully human anti-interleukin-17A monoclonal antibody, has demonstrated superior efficacy to ustekinumab in the phase 3b CLEAR study of moderate to severe plaque psoriasis. Here, we report 16-week results from CLARITY, a second head-to-head trial comparing secukinumab with ustekinumab.Methods: In the phase 3b CLARITY study, patients were randomized 1:1 to receive subcutaneous secukinumab 300 mg or ustekinumab per label. The co-primary objectives were to demonstrate the superiority of secukinumab over ustekinumab at Week 12 in relation to the proportion of patients with (1) 90% or more improvement from baseline Psoriasis Area and Severity Index (PASI 90) and (2) a score of 0/1 (clear/almost clear) on the modified Investigator’s Global Assessment (IGA mod 2011 0/1). Key secondary objectives were also assessed, as was Dermatology Life Quality Index (DLQI) 0/1 (no impact of skin disease on patients’ quality of life) response. Missing values were handled by multiple imputation except for DLQI 0/1, where last observation carried forward techniques were utilized.Results: Both co-primary objectives were met: secukinumab was superior to ustekinumab for the proportion of patients achieving a PASI 90 (66.5% vs. 47.9%) and IGA mod 2011 0/1 response (72.3% vs. 55.4%) at Week 12 (p < 0.0001). PASI 90 responses were greater with secukinumab compared to ustekinumab from as early as Week 4 (16.7% vs. 4.0%) and out to Week 16 (76.6% vs. 54.2%). Similarly, IGA mod 2011 0/1 findings were greater with secukinumab at Week 4 (26.9% vs. 7.8%) and at Week 16 (78.6% vs. 59.1%). DLQI 0/1 response rates were also greater with secukinumab compared to ustekinumab at Week 4 (33.9% vs. 18.0%), Week 12 (64.0% vs. 51.7%), and Week 16 (68.4% vs. 55.9%).Conclusion: The results of this study confirm the superior efficacy of secukinumab over ustekinumab in treating patients with moderate to severe psoriasis.Trial Registration: Clinicaltrials.gov Identifier, NCT02826603.Funding: Novartis Pharma AG, Basel, Switzerland. [ABSTRACT FROM AUTHOR]

Introduction: Psoriatic arthritis (PsA) is a chronic, inflammatory arthritis that affects an estimated 30% of patients with psoriasis. PsA is underdiagnosed in primary care and dermatology clinics due to a variety of reasons, including failure of healthcare providers to ask about symptoms, overlap of symptoms and signs with other rheumatologic conditions, and lack of a specific diagnostic test. A delay in PsA diagnosis and treatment, even as short as 6 months, can lead to decreased quality of life, increased joint damage, and worse long-term physical function. In this study, we sought to identify the clinical and genetic factors that help discriminate patients with PsA from those with cutaneous psoriasis only.Methods: We analyzed a cohort of 974 psoriasis patients at an academic medical center, of whom 175 had confirmed PsA, and performed univariate, multivariate, and predictive modeling to determine factors associated with PsA.Results: The univariate analysis revealed significant positive associations of PsA with age, nail involvement, scalp involvement, skin fold involvement, elbow/knee involvement, psoriasis severity, plaque subtype, erythrodermic subtype, hypertension, type 2 diabetes, and coronary artery disease, and a significant negative association of PsA with the human leukocyte antigen (HLA)-C*06:02 allele. In the multivariate analysis, nail involvement, type 2 diabetes, and pustular psoriasis remained significantly associated with PsA, while HLA-C*06:02 positivity remained protective. There was a trend towards an association of PsA with older age, younger age of psoriasis onset, and skin fold involvement, while there was protective trend for smoking. A predictive model including both clinical and genetic factors showed reasonable discriminative ability between psoriasis and PsA, with an area under the curve of 0.87 for a receiver operating characteristic curve.Conclusion: This study identified a number of clinical and genetic features that could help stratify patients who are at higher risk for having PsA and for whom rheumatology referral may be beneficial. [ABSTRACT FROM AUTHOR]

Introduction: Data regarding disease burden and quality of life (QoL) for patients with psoriasis from Russia are limited. The objective of this study was to describe the demographic and clinical characteristics, comorbidities, and treatment patterns of systemic therapy eligible psoriasis patients in Russia in order to assess the impact of psoriasis on the QoL and work productivity of the patients and to evaluate patient/dermatologist concordance on disease severity, signs/symptoms, and satisfaction with psoriasis treatment.Methods: Data were collected by the Growth from Knowledge Disease Atlas global real-world evidence programme from nine countries. The data from the Russian population are presented here. Adult patients who had a current or prior history of moderate-to-severe psoriasis and were receiving prescription treatment at the time of the survey were included. Dermatologist-reported data on disease severity, symptoms, comorbidities, and treatment as well as patient-reported data on QoL and work productivity were collected. Descriptive analysis of the data was conducted. Patient/dermatologist concordance was assessed using Cohen’s κ.Results: A total of 300 patients from Russia were included. The mean Psoriasis Area and Severity Index score was 9.0 and the mean disease duration was 9.9 years. The proportion of patients with itch, skin pain, and comorbidities increased as current psoriasis severity increased. The disease had a negative impact on patients’ QoL (mean Dermatology Life Quality Index score: 7.1) and work productivity (33.2% drop in work productivity), which further deteriorated as disease severity increased. A large proportion of the enrolled patients (60%) were treated with topical agents only. Overall, the level of concordance between patients and their dermatologists regarding psoriasis severity and satisfaction with overall disease control achieved was low.Conclusion: Results demonstrate a substantial disease burden on psoriasis patients in Russia, despite receiving treatment for their psoriasis, as well as low patient/dermatologist concordance of views on treatment outcomes. These findings also highlight a need to further incorporate the patient’s views into treatment decision-making in Russia.Funding: Novartis Pharma AG, Basel, Switzerland. [ABSTRACT FROM AUTHOR]

Genital psoriasis affects approximately 63% of psoriasis patients at least once in their lifetime. More than any other area on the body, genital lesions significantly impair patients’ psychologic well-being and quality of life. We aimed to systematically review the published evidence on the safety, efficacy, and tolerability of treatments of genital psoriasis and synthesize the available clinical data. A total of 1 randomized controlled trial, 11 open-label studies, and 26 case reports were included in our analysis, representing a total of 458 patients, of which 332 were adults and 126 were children. Topical corticosteroids were commonly used first-line for genital psoriasis and were well tolerated. Nonsteroidal agents, such as topical calcineurin inhibitors or vitamin D analogs, were also efficacious, but were often irritating. One systemic agent, ixekizumab, demonstrated efficacy in reducing genital psoriasis symptoms in a large, randomized, placebo-controlled trial. Various systemic and topical medications may improve genital psoriasis lesions, but there is a lack of high-quality evidence to guide clinical decision-making. Specific reporting of efficacy for genital psoriasis in larger controlled studies of psoriasis treatments are necessary to improve the available evidence regarding the optimal treatment regimen for genital psoriasis. [ABSTRACT FROM AUTHOR]

Psoriasis is a chronic inflammatory autoimmune disease with undefined etiology. It affects 2-3% of the worldwide population. The unsatisfactory outcome of variable treatments of the disease is partially due to the poor compliance of the present therapies with more or less side effects. As known, the human amniotic membrane is a popular intervention for many diseases. Amniotic membrane has been found recently to possess antimicrobial, anti-inflammatory and immunosuppressive properties. The irradiated amniotic membrane was used in this study as a topical application for 4 weeks on localized lesions in cases of mild psoriasis. The results presented herein provide a solid basis for the amniotic membrane to be used as a promising intervention for psoriasis treatment in the future. [ABSTRACT FROM AUTHOR]

Psoriatic arthritis (PsA) is rarely assessed in psoriasis randomized controlled trials (RCT); thus, the effect of psoriasis therapy on PsA is unknown. The International Dermatology Outcome Measures (IDEOM) has included “PsA Symptoms” as part of the core domains to be measured in psoriasis RCT. This study aimed to achieve consensus about screening for PsA and how to measure for “PsA Symptoms” in psoriasis RCT. At the IDEOM 2017 Annual Meeting, stakeholders voted on the role of PsA screening in psoriasis RCT. To select measures for “PsA Symptoms”, we adapted the Consensus-Based Standards for the Selection of Health Measurement Instruments (COSMIN) guidelines. Three potential measures were selected. At the meeting, stakeholders voted on the validity, feasibility, and responsiveness of these measures. Of the 47 stakeholders, 93% voted that all psoriasis trial participants should be screened for PsA. “PsA Symptoms” measures included Patient Global (PG)-arthritis, Routine Assessment Patient Index Data (RAPID)-3, and Psoriatic Arthritis Impact of Disease (PsAID)-9. During the voting, more than 50% of the voters agreed that RAPID3 and PsAID9 were good measures for PsA Symptoms, able to capture all its essential elements. PsAID9 was considered the most feasible instrument, followed by RAPID3 and PG-arthritis, respectively. Finally, most participants agreed that RAPID3 and PsAID9 were responsive measures. Most study participants voted that all subjects in a psoriasis clinical trial should be screened for PsA. RAPID3 and PsAID9 outperformed PG-arthritis in measuring PsA Symptoms. This will be followed by a Delphi survey involving a larger stakeholder group. [ABSTRACT FROM AUTHOR]

The article focuses on numerous effective treatments that patients with psoriasis do not need to use complementary and alternative medicines (CAMs) and the practice suggests that patients with psoriasis frequently do use CAMs. Topics include the performed an observational, cross-sectional, noncomparative, multicenter study in France between October 2018 and March 2019, and the study has received Ethics Committee approval.

Background and Objectives: Ustekinumab is used to treat moderate-to-severe psoriasis by blocking the interleukin-12/23 pathway, which is also essential against intracellular pathogens. Because there is a high prevalence of hepatitis B viral infection in Taiwan, the expected risk of reactivation is higher among ustekinumab-treated patients. We performed this study to investigate the risk of hepatitis reactivation.Subjects and Methods: Patients with psoriasis treated with ustekinumab from October 2011 to June 2016 were enrolled in a prospective cohort study. All patients were tested for hepatitis B serology and serum viral DNA at baseline. For those positive for hepatitis B surface antigen (HBsAg) or hepatitis B core antibodies (anti-HBc) testing for HBV DNA was conducted at least annually. An increase of HBV DNA > 2 log scale or emergence of HBV DNA were defined as reactivation. The primary outcome of this study was HBV reactivation.Results: Ninety-three psoriasis patients receiving ustekinumab were included. The average duration of treatment and follow-up was 24 ± 12 months. There were 39 patients classified as naïve to HBV or vaccinated, and none of these patients had HBV reactivation. Among the remaining 54 patients classified as inactive HBV carriers, resolved HBV infection, or isolated anti-HBc positivity, only 3 patients experienced virologic reactivation, and none had liver failure.Conclusion: The study outcomes indicate that ustekinumab could be safe for psoriasis patients since none developed persistent hepatitis or acute liver failure during therapy. However, the re-appearance of plasma HBV DNA requires appropriate monitoring of HBV viral load during ustekinumab treatment. [ABSTRACT FROM AUTHOR]

In psoriasis, several patient-relevant treatment goals must be met to be able to consider a treatment beneficial. To assess treatment benefit, the validated questionnaire Patient Benefit Index (PBI) can be used. Its global score summarizes the degree of patient-relevant treatment goals achieved after treatment, weighted by their individual importance on rating scales. These treatment goals have empirically been assigned to five dimensions. While the weighting procedure of the PBI provides information about the importance patients attach to treatment goals on a rating scale from 0 to 4, methods of preference elicitation provide information on how patients would trade off certain treatment goals against each other. However, since the treatment goals defined in the PBI often overlap conceptually, the dimensions of the PBI might be more suitable for exploration in preference elicitation methods. We used an analytic hierarchy process (AHP) and a discrete choice experiment (DCE) to generate preference-based importance weights for the PBI dimensions, and compared these weights to those derived from the rating scales. We were further interested in the effect of importance weights on the calculation of the PBI score. A total of 120 patients with psoriasis completed a questionnaire at baseline, including AHP, DCE and the rating scales, and at follow-up, regarding the attainment of treatment goals, to calculate the PBI score. In contrast to the results derived from the average rating scores, use of AHP and DCE resulted in both similar importance weights and rankings of dimensions. Presumably, patients rated treatment goals differently than the respective dimension they belong to. However, the differently calculated importance weights led to similar values of the PBI score. Our findings nevertheless provide clear evidence that, regardless of the method used, the importance of treatment goals differs between psoriasis patients, and this should be reflected in treatment decisions. [ABSTRACT FROM AUTHOR]

Introduction: Clinical trials have shown brodalumab to have better efficacy than ustekinumab for the treatment of moderate-to-severe psoriasis. An estimation of the cost-effectiveness of brodalumab vs. ustekinumab is warranted and may be useful for treatment decision-making processes, especially in the context of the cost considerations of the current US healthcare system. Therefore, we compared the cost-effectiveness of brodalumab with ustekinumab for treatment of moderate-to-severe psoriasis in biologic-naïve and biologic-experienced patients in the USA.Methods: An Excel-based economic model was developed to estimate and compare total annual costs to health plans associated with treatment with brodalumab vs. ustekinumab per achievement of Psorasis Area and Severity Index (PASI) 75, 90, and 100 for patients with moderate-to-severe psoriasis.Results: For treatment with brodalumab vs. ustekinumab, total annual treatment costs per PASI 75, 90, and 100 were $31,106, $57,776, and $163,069, respectively, lower for a patient naïve to prior biologic treatment; they were $40,535, $65,472, and $223,610, respectively, lower for a patient experienced with prior biologic treatment. In an additional analysis among patients with and without prior biologic failure, they were $52,822, $93,309, and $365,606, respectively, lower for a patient with failure and they were $31,660, $57,128, and $164,996, respectively, lower for a patient without failure.Conclusion: Compared to ustekinumab, treatment with brodalumab was associated with better cost-effectiveness ratios for biologic-naïve and experienced-patients and also patients with and without prior biologic treatment failure. The greater cost-effectiveness of brodalumab was most prominent for biologic-experienced and prior biologic treatment failure patients.Funding: Ortho Dermatologics. [ABSTRACT FROM AUTHOR]

Introduction: To design and implement a novel cloud-based digital platform that allows psoriatic patients and researchers to engage in the research process.Methods: Citizen Pscientist (CP) was created by the National Psoriasis Foundation (NPF) to support and educate the global psoriatic disease community, where patients and researchers have the ability to analyze data. Psoriatic patients were invited to enroll in CP and contribute health data to a cloud database by responding to a 59-question online survey. They were then invited to perform their own analyses of the data using built-in visualization tools allowing for the creation of “discovery charts.” These charts were posted on the CP website allowing for further discussion.Results: As of May 2017, 3534 patients have enrolled in CP and have collectively contributed over 200,000 data points on their health status. Patients posted 70 discovery charts, generating 209 discussion comments.Conclusion: With the growing influence of the internet and technology in society, medical research can be enhanced by crowdsourcing and online patient portals. Patient discovery charts focused on the topics of psoriatic disease demographics, clinical features, environmental triggers, and quality of life. Patients noted that the CP platform adds to their well-being and allows them to express what research questions matter most to them in a direct and quantifiable way. The implementation of CP is a successful and novel method of allowing patients to engage in research. Thus, CP is an important tool to promote patient-centered psoriatic disease research. [ABSTRACT FROM AUTHOR]

Psoriasis vulgaris (PsV) is a common, chronic skin disease with a complex genetic and environmental etiology. We investigated, in 461 psoriatic patients and 454 healthy controls, the associations with psoriasis of four single-nucleotide polymorphisms (SNPs) from the psoriasis susceptibility 1 (PSORS1) interval: rs1062470 (PSORS1C1/CDSN), rs887466 (PSORS1C3), rs2894207 and rs10484554 (LOC105375015). The minor alleles of three SNPs (rs1062470A, rs2894207C and rs10484554T) strongly increased the disease risk (OR = 2.17, p < 0.0001; OR = 2.33, p < 0.0001 and OR = 2.68, p < 0.0001, respectively), whereas the minor A allele of rs887466 exerted a protective effect (OR = 0.73, p = 0.001). The strength of association for SNPs was the highest in patients with very early onset psoriasis (≤ 20 years), while in late onset psoriasis (> 40 years) the association was the weakest. The haplotype rs1062470A/rs887466G/rs2894207C/rs10484554T highly significantly increased the disease risk (OR = 3.58, p = 8.0e−027), while the haplotypes rs1062470G/rs887466A/rs2894207T/rs10484554C and rs1062470G/rs887466G/rs2894207T/rs10484554C were strongly protective (OR = 0.65, p = 0.002 and OR = 0.55, p = 2.4e−009, respectively). Additionally, we showed a HLA-C*06:02-independent gender-related effect of the rs887466A allele which was protective against psoriasis in males (OR = 0.61, p = 9.2e−005), but not in females (p = 0.66). We also demonstrated a correlation of PASI score value with rs1062470 genotype, and again only in male patients (p = 0.006) and HLA-C*06:02-independent. Our results show, for the first time, the male-only associations of the PSORS1C3 gene with psoriasis risk and of the PSORS1C1/CDSN gene with severity of disease. However, the age dependent associations need to be validated in larger sample sizes as well as in other populations. [ABSTRACT FROM AUTHOR]