Psoriasis (Auckland, N.Z.)最新文献

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.

Psoriasis is a chronic immune-mediated inflammatory disease with significant medical and psychological comorbidities. In addition to having increased cardiovascular risk and mortality, psoriasis patients are more likely to be depressed, anxious, and endorse suicidal ideation than the general population. These patients often have low self-esteem and feel stigmatized due to their skin disease, which can prevent them from pursuing relationships, dating, and attending social activities. Up to 63% of adult psoriasis patients experience psoriatic lesions on their genital area during their lifetime, but often do not discuss these issues with their physicians due to embarrassment, stigmatization, or shyness about this sensitive location. However, psoriasis in sensitive areas, such as the genitals, may result in quality of life impairment greater than that of patients with psoriasis elsewhere on their body, particularly in respect to romantic relationships, intimacy, and sexual function. This article evaluates the current literature regarding the impact of genital psoriasis on the quality of life of affected patients.

Psoriatic arthritis (PsA) is a heterogeneous disease with several clinical subtypes including peripheral arthritis, dactylitis, enthesitis, nail disease, and axial arthritis. Nonsteroidal anti-inflammatory drugs, glucocorticoids, and conventional disease-modifying agents are used as first line in the treatment of active PsA. For moderate-to-severe PsA failing conventional therapy, antitumor necrosis factor inhibitors have historically been the drugs of choice. In recent years, novel interleukin-23/interleukin-17 pathway targets such as ustekinumab and secukinumab, and phosphodiesterase-4 inhibitor apremilast have been approved for use in the United States and Europe. Two sets of recommendations for the management of PsA were published in 2016 with consideration for these newer therapies. Since then, the results from a Phase III randomized controlled trial demonstrated that abatacept has efficacy in the treatment of PsA. Abatacept, a cytotoxic-T-lymphocyte-associated antigen 4 (CTLA-4)-Ig human fusion protein, acts to prevent naïve T-cell activation through the inhibition of the critical CD28 co-stimulatory signal. In the 2017 Active Psoriatic Arthritis Randomized Trial (ASTRAEA), 424 participants were randomized 1:1 to receive subcutaneous abatacept 125 mg weekly versus placebo. At week 24, 39.4% of those who received abatacept achieved a minimum of 20% improvement in the American College of Rheumatology (ACR) response compared to 22.3% in the placebo arm, a statistically significant finding (P<0.001). The 2011 Phase II study published by Mease et al demonstrated statistically significant improvements in the ACR20 response by week 169 in participants treated with intravenous abatacept 10 mg/kg (48%) and 30/10 mg/kg (42%) when compared with placebo (19%). This article reviews the data supporting the efficacy of abatacept in the management of PsA and attempts to place this agent in the context of other biologic disease-modifying antirheumatic drugs and targeted small molecules used in the treatment of patients with PsA.

Increasingly, existing evidence indicates that methotrexate-associated liver injury is related to comorbid risk factors such as diabetes, alcoholism, and obesity, rather than to methotrexate itself. Despite this fact, significant effort continues to be expended in the monitoring of low-dose methotrexate in patients with psoriasis. The gold standard investigation has been liver biopsy, but this is associated with significant morbidity and mortality. As methotrexate-induced liver injury is uncommon, the risk/benefit ratio of liver biopsy has been questioned. Fortunately, a number of new technologies have been developed for the diagnosis of chronic liver disease, including transient elastography (TE). TE is a type of shear wave ultrasound elastography, which measures the speed of shear waves used to estimate hepatic tissue stiffness. Several meta-analyses show very high pooled sensitivity and specificity for the diagnosis of hepatic cirrhosis (87% and 91%, respectively) in a variety of chronic liver disorders. It has a negative predictive value for cirrhosis of >90% and a positive predictive value of 75%. Recent European guidelines now advocate the use of TE as the first-line test for the assessment of fibrosis in alcohol- or hepatitis-related liver disease, including nonalcoholic fatty liver disease (NAFLD). As the prevalence of obesity and metabolic syndrome, including NAFLD, is significantly elevated in patients with psoriasis, TE may be worth considering as a routine investigation for any patient with psoriasis. Although high-quality studies comparing TE with standard liver biopsy in the monitoring of psoriatics on low-dose methotrexate are lacking, the evidence from multiple small cohort studies and case series demonstrates its effectiveness. A recent Australasian position statement recommends that TE should be considered as a routine investigation for monitoring methotrexate therapy, repeated every 3 years if kPa <7.5 and yearly if kPa >7.5. Liver biopsy should be considered for patients with a kPa >9.5.

Objective: To explore differences in response to a low dosage regimen of infliximab with an escalating dosage in comparison to a standard dosage of etanercept and adalimumab in patients with psoriatic arthritis (PsA).

Methods: Biologically naïve PsA patients who were beginning anti-TNF-α therapy were selected from the ICEBIO registry. Demographics and clinical differences were compared in four treatment groups: infliximab <4 mg/kg; infliximab >4 mg/kg; etanercept or adalimumab at baseline and on follow-up (6 and 12 months, last visit). The Kruskal-Wallis rank sum test was used for comparison of the groups and the Wilcoxon test to compare the two infliximab dosage regimens.

Results: One hundred and eighty-five patients (61% female) were identified; 84 patients received infliximab, 66 etanercept, and 35 adalimumab. A total of 19% of the patients treated with infliximab escalated their dosage ≥4 mg/kg. No significant differences were observed at baseline in respect to visual analog scale (VAS) pain, VAS fatigue, Health Assessment Questionnaire, C-reactive protein (CRP), numbers of swollen or tender joints, or Disease Activity Score (DAS) 28-CRP values. A similar treatment response was observed in all four treatment groups on follow-up.

Conclusion: In respect to treatment effects, a low dosage of infliximab with possible escalating dosage is acceptable for the majority of PsA patients who are in need of biological treatment.

Purpose: Several studies have suggested that an HLA-Cw6+ allele can predict an improved outcome of treatment in psoriasis patients. The aim of the study was to assess whether the published association between HLA-Cw6 allele carriers and response to ustekinumab has the potential to impact treatment decisions.

Patients and methods: Differences in Psoriasis Activity and Severity Index 50, 75, and 90; Nail Psoriasis Severity Index; and Dermatology Life Quality Index at 16 weeks were evaluated between HLA-Cw6 allele carriers vs. non-carriers. Thirty patients with moderate-to-severe psoriasis under treatment with ustekinumab were included in our study.

Results: There was no difference between the two groups with respect to Psoriasis Activity and Severity Index 50, 75, and 90 or in terms of change in Nail Psoriasis Severity Index or Dermatology Life Quality Index.

Conclusion: In our retrospectively analyzed cohort, we could not detect the previously reported better response in HLA-Cw6+ vs. HLA-Cw6- patients.

The recent advances in the understanding of psoriasis pathogenesis have clarified the pivotal role of interleukin (IL)-23. It is a heterodimeric cytokine consisting of two subunits, the unique p19 and the p40, which are shared with IL-12. The basic role of IL-23 in psoriasis is the activation and maintenance of the T-helper 17 pathway. New research findings indicate that IL-23 is more important than IL-12 in the pathogenesis of psoriasis. Based on that background, the selective targeting of the IL-23p19 subunit emerged as an attractive therapeutic option and led to the development of a new category of biologic agents. Three monoclonal antibodies that selectively inhibit the IL-23p19 subunit, guselkumab, tildrakizumab, and risankizumab, are in the pipeline for the treatment of moderate-to-severe psoriasis. In this article, we review the most recent efficacy and safety data regarding these IL-23p19 inhibitors.