Genetic Influence on Treatment Response in Psoriasis: New Insights into Personalized Medicine.

Psoriasis is a chronic inflammatory disease with an established genetic background. The HLA-Cw*06 allele and different polymorphisms in genes involved in inflammatory responses and keratinocyte proliferation have been associated with the development of the disease. Despite the effectiveness and safety of psoriasis treatment, a significant percentage of patients still do not achieve adequate disease control. Pharmacogenetic and pharmacogenomic studies on how genetic variations affect drug efficacy and toxicity could provide important clues in this respect. This comprehensive review assessed the available evidence for the role that those different genetic variations may play in the response to psoriasis treatment. One hundred fourteen articles were included in this qualitative synthesis. VDR gene polymorphisms may influence the response to topical vitamin D analogs and phototherapy. Variations affecting the ABC transporter seem to play a role in methotrexate and cyclosporine outcomes. Several single-nucleotide polymorphisms affecting different genes are involved with anti-TNF-α response modulation (TNF-α, TNFRSF1A, TNFRSF1B, TNFAIP3, FCGR2A, FCGR3A, IL-17F, IL-17R, and IL-23R, among others) with conflicting results. HLA-Cw*06 has been the most extensively studied allele, although it has only been robustly related to the response to ustekinumab. However, further research is needed to firmly establish the usefulness of these genetic biomarkers in clinical practice.

Cardiovascular Screening Practices and Statin Prescription Habits in Patients with Psoriasis among Dermatologists, Rheumatologists and Primary Care Physicians.

Patients with psoriasis have a higher prevalence of cardiovascular risk factors. This study evaluated cardiovascular screening practices and statin prescribing habits among dermatologists, rheumatologists and primary care physicians (PCPs) through an online questionnaire, which was distributed through the Spanish scientific societies of the above-mentioned specialties. A total of 299 physicians (103 dermatologists, 94 rheumatologists and 102 PCPs) responded to the questionnaire. Of these, 74.6% reported screening for smoking, 37.8% for hypertension, 80.3% for dyslipidaemia, and 79.6% for diabetes mellitus. Notably, only 28.4% performed global screening, defined as screening for smoking, hypertension, dyslipidaemia, and diabetes mellitus by the same physician, and 24.4% reported calculating 10-year cardiovascular disease (CVD) risk, probably reflecting a lack of comprehensive cardiovascular risk assessment in these patients. This study also identified unmet needs for awareness of cardiovascular comorbidities in psoriasis and corresponding screening and treatment recommendations among PCPs. Of PCPs, 61.2% reported not being aware of the association between psoriasis and CVD and/or not being aware of its screening recommendations, and 67.6% did not consider psoriasis as a risk-enhancing factor when deciding on statin prescription. Thirteen dermatologists (12.6%) and 35 rheumatologists (37.2%) reported prescribing statins. Among those who do not prescribe, 49.7% would be willing to start their prescription.

Advances of Genomic Medicine in Psoriatic Arthritis.

Psoriatic arthritis (PsA) is a common type of inflammatory arthritis found in up to 40% of patients with psoriasis. Although early diagnosis is important for reducing the risk of irreversible structural damage, there are no adequate screening tools for this purpose, and there are no clear markers of predisposition to the disease. Much evidence indicates that PsA disorder is complex and heterogeneous, where genetic and environmental factors converge to trigger inflammatory events and the development of the disease. Nevertheless, the etiologic events that underlie PsA are complex and not completely understood. In this review, we describe the existing data in PsA in order to highlight the need for further research in this disease to progress in the knowledge of its pathobiology and to obtain early diagnosis tools for these patients.

Impact of Biological Agents on Imaging and Biomarkers of Cardiovascular Disease in Patients with Psoriasis: A Systematic Review and Meta-Analysis of Randomized Placebo-Controlled Trials.

BACKGROUND: The effect of biologics on the risk for cardiovascular disease in patients with psoriasis is still unclear despite their widespread use. OBJECTIVE: The objective of this study was to examine the impact of licensed biological therapies on imaging and biomarkers of cardiovascular disease risk in patients with psoriasis by a systematic review and meta-analysis of placebo-controlled trials. METHODS: A comprehensive search of studies published before 1 June 2020 was performed in Medline-Ovid, EMBASE, and CENTRAL using a predefined strategy to identify relevant articles. RESULTS: Five studies were included for the final examination, and two studies were included in the meta-analysis. We did not find a significant reduction in aortic vascular inflammation in patients treated with adalimumab compared with those who received placebo at weeks 12-16. There was no beneficial effect on imaging biomarkers (aortic vascular inflammation or flow-mediated dilatation) of cardiovascular disease risk in patients exposed to biological therapies (adalimumab and secukinumab) compared with those exposed to placebo, except for ustekinumab showing a reduction in aortic vascular inflammation at week 12 but not at week 52 after the open-label extension period. The strongest reduction in blood-based cardiometabolic risk biomarkers was observed with adalimumab (CRP, TNF-α, IL-6, and GlycA) and phototherapy (CRP and IL-6) compared with that observed with placebo. CONCLUSIONS: Randomized controlled trials show that ustekinumab reduces aortic vascular inflammation and that TNF-α inhibitors and phototherapy reduce CRP and IL-6. These surrogate marker findings require randomized controlled trials evaluating cardiovascular events to inform clinical practice.

Insulin resistance in lean and overweight non-diabetic Caucasian adults: Study of its relationship with liver triglyceride content, waist circumference and BMI.

AIMS: Insulin resistance is the pathophysiological precursor of type 2 diabetes mellitus (DM-2), and its relationship with non-alcoholic fatty liver disease (NAFLD) has been widely studied in patients with obesity or metabolic syndrome using not only ultrasound but also liver biopsies or proton magnetic resonance spectroscopy (H1-MRS) to assess liver fat content. In contrast, there are no studies on insulin resistance and NAFLD in lean or overweight Caucasian individuals using H1-MRS or liver biopsies for the quantification of hepatic triglyceride content. Our objectives were to study the presence of insulin resistance in lean and overweight Caucasian adults and investigate its possible relationship with liver triglyceride content, waist circumference (as proxy of visceral adiposity), BMI, and cardiometabolic risk factors. METHODS: A cross-sectional study was conducted in 113 non-obese, non-diabetic individuals classified as overweight (BMI 25-29.9 kg/m2) or lean (BMI 19.5-24.9 kg/m2). Hepatic triglyceride content was quantified by 3T H1-MRS. NAFLD was defined as hepatic triglyceride content >5.56%. Insulin resistance (HOMA-IR), serum adiponectin, and tumor necrosis factor (TNF) were determined. RESULTS: HOMA-IR was significantly correlated with hepatic triglyceride content (r:0.76; p<0.0001). The lean-with-NAFLD group had significantly higher HOMA-IR (p<0.001) and lower serum adiponectin (p<0.05) than the overweight-without-NAFLD group. Insulin resistance was independently associated with NAFLD but not with waist circumference or BMI. Regression analysis showed hepatic triglyceride content to be the most important determinant of insulin resistance (p<0.01). CONCLUSIONS: Our findings suggest that NAFLD, once established, seems to be involved in insulin resistance and cardio-metabolic risk factors above and beyond waist circumference and BMI in non-obese, non-diabetic Caucasian individuals.