Psoriasis (Auckland, N.Z.)最新文献

Plaque psoriasis (PsO) is a chronic inflammatory skin disorder that may be associated with several comorbidities, including arthritis. The increasing knowledge of psoriasis pathogenesis led to the identification of novel targeted therapeutic interventions. Among them, anti-IL-17A and anti-IL-17F antibodies are currently being investigated for the treatment of PsO and/or psoriatic arthritis (PsA). Bimekizumab is one of these agents, capable ofsimultaneously neutralizing both IL-17A and IL-17F cytokines. In this review we included preclinical and clinical data related to this highly promising agent that shows a peculiar molecular structure differing from other bispecific agents.

Psoriasis is a chronic, debilitating, immune-mediated, systemic inflammatory disease affecting mainly skin, nails, and joints. Several therapeutic modalities are available depending on the severity of the disease. Long-term use of these drugs results in unwanted effects and toxicities. Recently, itolizumab, a humanized monoclonal immunoglobulin G1 antibody to CD6, has shown appreciable clinical effects and safety profile in patients with moderate-to-severe chronic plaque psoriasis. A literature search was conducted using the keywords "anti-CD6", "psoriasis", "phase trials", "case series", and "case reports". The data from all studies conducted in India on efficacy of itolizumab in psoriasis and published before September 2017 were collected. This article provides an overview of the clinical data obtained in these published articles. Itolizumab has immunomodulatory and anti-inflammatory effects. It is efficacious and provides a good duration of remission, and hence represents a new biological agent that could be added to the therapeutic armamentarium of psoriasis.

Purpose: Psoriasis vulgaris (PV) is an autoimmune-related chronic inflammatory disease of the skin, with both vascular and metabolic effects. Aggravating factors have been identified that initiate and maintain inflammation, including expression of Th1-, Th17-, and Th22-cell derived cytokines. Recently, we showed that the evolutionarily ancient and highly conserved damage-associated molecular pattern molecule "high mobility group box 1 (HMGB1)" is significantly increased in the serum of PV patients with disease progression and is decreased under standard therapies.

Materials and methods: To better understand the role of HMGB1 in the pathogenesis of PV, we recruited 22 untreated psoriatic patients with either mild or severe disease, defined by the Psoriasis Area Severity Index. We assessed HMGB1 and receptor for advanced glycation end products (RAGE) expression in the skin by immunohistochemistry and analyzed the immune-phenotype of Treg and Th17 cells by flow cytometry.

Results: We found increased staining for HMGB1 in the dermis of psoriatic plaques in comparison to uninvolved skin of patients with PV. In addition, the major histocompatibility complex class III-encoded DNA and HMGB1 RAGE, induced by HMGB1, were highly expressed on psoriatic CD8+ T cells and CD4+ Treg. High expression of HMGB1 in the lesional skin was associated with even higher expression of its receptor, RAGE, on the cell surface of keratino-cytes in patients with severe PV.

Conclusion: The presence of HMGB1 and RAGE signaling may impact orchestration of chronic inflammation in PV which might have implications for Treg and Th17 cells.

According to the WHO, sexual health is not merely the absence of disease. Sexual dysfunction may be present in 40.8% of psoriasis patients, furthermore, 68% prevalence was found in Brazilian women with psoriasis. The moderate prevalence of psoriatic lesions in the genital area (35%-42%) does not explain the alarming prevalence of sexual dysfunction. Other factors, such as anxiety, depression, and also psoriasis treatment may contribute to its development. Likewise, atherosclerosis of the pelvic vasculature is involved in the pathogenesis of erectile dysfunction. Risk factors for erectile dysfunction tend to be confused with the comorbidities seen in psoriasis patients. We also highlight that it may serve as a marker of cardiovascular risk.

Psoriasis is a common chronic immune-mediated skin disease, with systemic involvement and significant impact in patients' quality of life. Several highly specific treatments have been developed over the years, such as tumor necrosis factor-α inhibitors, a nonselective IL-23 inhibitor (ustekinumab), and most recently IL-17 inhibitors. Risankizumab is a monoclonal antibody which targets IL-23p19 without binding IL-12. This novel therapeutic approach is expected to have advantages over the recently approved anti-IL-17 agents, such as the avoidance of Candida infections and neutropenia. In addition, unlike ustekinumab, the selective inhibition of IL-23 may preserve IL-12-dependent functions such as protection against infections and tumor immune surveillance. Risankizumab showed an excellent efficacy when compared to placebo and ustekinumab, with higher Psoriasis Area Severity Index (PASI) 75, PASI 90, and PASI 100 rates, along with a convenient every 12-week maintenance dosing regimen. Overall, risankizumab was well tolerated and the most common adverse event was upper respiratory tract infection. In the near future, further data will be available not only in psoriasis but also in Crohn's disease and psoriatic arthritis fields. Head-to-head trials comparing risankizumab with other IL-23 inhibitors and with IL-17 inhibitors will be crucial to reveal the role of risankizumab in the treatment of psoriasis.

Secukinumab is a human monoclonal antibody targeting IL-17A that has been approved for three indications: moderate-to-severe plaque psoriasis, psoriatic arthritis, and ankylosing spondylitis. In Phase III clinical trials for each of these three indications, secukinumab has proven to be both highly efficacious and well-tolerated. However, several biologic medications are currently approved for the treatment of moderate-to-severe plaque psoriasis, and many demonstrate excellent efficacy and safety. Due to this wide selection, it is often unclear how to choose biologics for specific patients. Important considerations in biologic selection include clinical efficacy, safety, cost, convenience, onset of action, and management of comorbid disease. This article aims to outline the key considerations in patient selection for the treatment of plaque psoriasis with secukinumab.

Background: The product of Physician Global Assessment and Body Surface Area (PGA × BSA) is a new outcome measure for psoriasis severity and response to therapy. The objective of this study was to evaluate PGA × BSA as an alternative to Psoriasis Area and Severity Index (PASI) for psoriasis assessments.

Methods: The relationship between PASI and PGA × BSA was assessed in a post hoc analysis of pooled data from the PRISTINE (NCT00663052) and PRESTA (NCT00245960) trials in patients with moderate-to-severe psoriasis who received etanercept 50 mg/week. Data were analyzed using Spearman and intra-class correlation coefficients, effect sizes, scatterplots, Bland-Altman plots, and Kappa statistics.

Results: Spearman correlations at baseline, week 12, and week 24 were strong for PGA × BSA versus PASI (r=0.78, 0.87, and 0.90, respectively; all P<0.0001) as were intra-class correlations (0.76 [95% confidence interval 0.73-0.80], 0.80 [0.76-0.83], and 0.85 [0.82-0.87], respectively). The effect size was -1.53 for PASI and -0.94 for PGA × BSA (baseline to week 24). Scatterplots and Bland-Altman plots detected a trend across the range of measurement. Kappa statistics (at 12 and 24 weeks) between PASI50/75/90 and 50/75/90% improvement in PGA × BSA showed good agreement (0.58-0.69 at week 12 and 0.63-0.67, respectively; all P<0.0001). At baseline, the Spearman correlation coefficients were 0.96, 0.51, 0.19, and 0.17 for PGA × BSA versus BSA, PGA, Patient Global Assessment, and Dermatology Life Quality Index, respectively (all P<0.001).

Conclusion: PGA × BSA has advantages over PASI for measuring moderate-to-severe psoriasis; it is intuitive, sensitive, and easy to use.

Background: Psoriasis is a dermatological disorder with a multifactorial origin and is associated with many biochemical and immunological changes.

Purpose: This study aimed to examine the association of serum ADA activity, uric acid (UA), and high-sensitivity CRP (hs-CRP) with psoriasis and the role of ADA in disease severity.

Materials and methods: In this comparative cross-sectional study, 50 clinically and histopathologically diagnosed psoriasis patients and 50 age- and sex-matched healthy controls were enrolled. Blood samples were taken and analysis of the biochemical parameters was performed according to Giuisti and Galanti method, uricase and ELISA technique for ADA activity, UA, and hs-CRP, respectively. The severity of the disease was scored according to Psoriasis Area and Severity Index (PASI). Statistical analysis of differences within and between the study groups was carried out using the Student's t-test, one-way post hoc ANOVA, and Pearson's correlation. Linear regression was used to establish the independent association of ADA with disease severity.

Results: The serum ADA activity, UA, and hs-CRP levels of the psoriatic patients were found to be significantly higher (P<0.001). hs-CRP was positively correlated with ADA and UA in patients (P<0.001). There was no significant difference in total cholesterol, low-density lipoprotein, and triacylglycerol in psoriasis patients, whereas we noted a decreased high-density lipoprotein level in psoriasis patients as compared to controls. Linear regression showed that ADA was independently associated with the disease severity and was statistically significant (P<0.001).

Conclusion: ADA activity was positively and significantly associated with the severity of psoriasis, therefore, it could be suggested as a marker for disease severity in psoriasis patients.

Plaque psoriasis is an immune-mediated skin disease that affects roughly 3% of adults in the United States. Advances over the past 20 years in understanding the immune-mediated pathophysiology of psoriasis have led to the development of targeted biologic therapies for this condition. Currently, biologic medications approved for the treatment of plaque psoriasis include tumor necrosis factor α inhibitors, interleukin (IL)-17 or IL-17 receptor inhibitors, IL-12/23 inhibitors, and IL-23 inhibitors. Tildrakizumab-asmn is a monoclonal antibody that targets the p19 subunit of IL-23 and is approved for use in adult patients with moderate-to-severe plaque psoriasis who are candidates for systemic therapy or phototherapy. This article reviews the current pharmacologic, efficacy, and safety data on tildrakizumab-asmn.