Dose reduction is a feasible strategy in patients with plaque psoriasis who achieve sustained response with secukinumab: a retrospective, multicenter cohort study in daily practice setting.

Background: Biological therapy dose modification is a common practice in the long-term treatment of plaque psoriasis.

Objective: The objective of the study was to determine prevalence, characteristics of patients, effectiveness, treatment survival of secukinumab dose reduction (SEC-DR) strategy and assess its safety and cost implications.

Methods: A retrospective, observational, multicenter cohort study was conducted in patients with plaque psoriasis treated with secukinumab and up to 2 years of follow-up.

The / rs1990760 Gene Variant (946Thr) Differentiates Early- vs. Late-Onset Skin Disease and Increases the Risk of Arthritis in a Spanish Cohort of Psoriasis.

The melanoma differentiation-associated protein 5 (MDA5; encoded by the gene) mediates the activation of the interferon pathway in response to a viral infection. This protein is also upregulated in autoimmune diseases and psoriasis skin lesions. gene variants that increase MDA5 activity have been associated with an increased risk for immune-mediated diseases, including psoriasis.

A quantitative systems pharmacology model for certolizumab pegol treatment in moderate-to-severe psoriasis.

Background: Psoriasis is a chronic immune-mediated inflammatory systemic disease with skin manifestations characterized by erythematous, scaly, itchy and/or painful plaques resulting from hyperproliferation of keratinocytes. Certolizumab pegol [CZP], a PEGylated antigen binding fragment of a humanized monoclonal antibody against TNF-alpha, is approved for the treatment of moderate-to-severe plaque psoriasis. Patients with psoriasis present clinical and molecular variability, affecting response to treatment.

Secukinumab is effective and safe in the long-term treatment of plaque psoriasis in a daily practice setting: Multicenter study in 384 Spanish patients.

The aim of the study was to assess the long-term effectiveness and safety of secukinumab in Spanish patients with moderate-to-severe psoriasis in a daily practice setting. Nationwide multicenter, observational, retrospective, non-interventional, single-cohort study including patients who initiated treatment with secukinumab in daily clinical practice conditions. Subjects were followed for a minimum of 3 months and a maximum of 24 months.

Potential Differences in the Cardiometabolic Risk Profile of Patients with Psoriatic Disease according to Their HLA-C∗06 Status.

The human leukocyte antigen-C∗06 (HLA-C∗06, formerly HLA-Cw6) is the main genetic biomarker in psoriatic disease. It has been related to several phenotypic traits in psoriatic disease, but its role in relation to cardiometabolic comorbidities is unknown at present. Here, we analyze the potential connections between this biomarker and the cardiometabolic profile of these patients.

Genome-wide association analysis of psoriasis patients treated with anti-TNF drugs.

While anti-TNF therapies are effective against psoriasis, 30%-50% of patients do not show an adequate response to these drugs. Different candidate-gene pharmacogenetics studies have identified single nucleotide polymorphisms that may predict anti-TNF drugs response in psoriasis. Nevertheless, only one paper has undertaken a pharmacogenomic approach failing to find significant biomarkers of biological drug response along the whole genome.

Gene Variant in the NF-B Pathway Inhibitor Distinguishes Patients with Psoriatic Arthritis within the Spectrum of Psoriatic Disease.

Background And Aims: The NF-B pathway has been implicated in the genetic aetiology of psoriatic disease. However, since most patients with arthritis have psoriasis, discerning the genetic contributions to both aspects of psoriatic disease is not easy. Our aim was to study the association of common polymorphisms in genes of the NF-B pathway in patients with psoriatic disease in order to dissect the contribution of this pathway in the appearance of each component (skin and joint) of the disease.

NFKBIZ and CW6 in Adalimumab Response Among Psoriasis Patients: Genetic Association and Alternative Transcript Analysis.

Background: Nuclear factor (NF)-κB is an essential mediator of the tumor necrosis factor (TNF) pathway, and has been implicated in psoriasis. NFKBIZ is a nuclear inhibitor of NF-κB with a prominent role in the pathogenesis of psoriasis. The genetic variation at the NFKBIZ gene has been associated with the risk of developing psoriasis, and could also contribute to defining the response to anti-TNF biological drugs.

Ustekinumab in psoriatic arthritis: need for studies from real-world evidence.

Ustekinumab (UST) is a recently approved drug for the treatment of psoriatic arthritis (PsA). The ACR response rates in randomized clinical trials (RCTs) with this drug have been slightly lower than that reported in RCTs of anti-TNF and anti-IL17 therapies. Therefore, the position that this drug may occupy in the treatment algorithms of PsA is not clear.

High rates of tuberculin skin test positivity due to methotrexate therapy: False positive results?

Rationale: The tuberculin skin test (TST) and interferon ? release assays (IGRAs) are commonly used for latent tuberculosis infection (LTBI) screening. Unexpectedly high TST positivity rates have been reported in patients with rheumatic diseases, and methotrexate is frequently used in this population. We hypothesized that methotrexate use could be associated with false-positive TST results.

Gene variants in the NF-KB pathway (NFKB1, NFKBIA, NFKBIZ) and their association with type 2 diabetes and impaired renal function.

The NF-kappaB pathway might play a role in the pathogenesis of renal disease and type 2 diabetes (T2DM). Our aim was to determine whether common polymorphisms in NF-kappaB genes were associated with impaired renal function and T2DM in a cohort of healthy elderly individuals. We studied 487 individuals, all Caucasian and aged 65-85 years.

NFKBIZ in Psoriasis: Assessing the association with gene polymorphisms and report of a new transcript variant.

The IκBζ protein (NFKBIZ gene) is a nuclear inhibitor of NF-κB and plays an important role in the pathogenesis of Psoriasis (Psor). We sought to determine whether common NFKBIZ variants were associated with the risk of developing Psor. A total of 392 patients and 336 controls were genotyped for a common intron 10 indel that could affect pre-mRNA splicing.

A Single Nucleotide Polymorphism in the Il17ra Promoter Is Associated with Functional Severity of Ankylosing Spondylitis.

The aim of this study was to identify new genetic variants associated with the severity of ankylosing spondylitis (AS). We sequenced the exome of eight patients diagnosed with AS, selected on the basis of the severity of their clinical parameters. We identified 27 variants in exons and regulatory regions.

KCNQ1 gene variants in the risk for type 2 diabetes and impaired renal function in the Spanish Renastur cohort.

Several common KCNQ1 gene polymorphisms have been associated with the risk of type 2 diabetes (T2DM) and diabetic nephropathy. This effect is explained by the role of the kcnq1 protein as a potassium channel that in the pancreatic beta-cells drives an electrical signal that facilitates glucose-stimulated insulin secretion. The KCNQ1 gene is also expressed in the kidney, and could thus be implicated in the risk of developing impaired renal function.

CDKAL1 gene variants affect the anti-TNF response among Psoriasis patients.

The heterogeneous response to anti-TNF biological drugs among Psoriasis (Psor) patients might be explained by gene variants linked to the risk for Psor. Common variants in the CDKAL1 gene have been associated with the risk of developing Psor. Our hypothesis was that these variants could also influence the response to anti-TNFs among Psor-patients.

Association between single nucleotide polymorphisms IL17RA rs4819554 and IL17E rs79877597 and Psoriasis in a Spanish cohort.

Background: The IL17 pathway plays an important role in the pathogenesis of psoriasis (PsO).

Objectives: To determine whether the variation at the IL17 pathway genes was linked to the risk for PsO or had an effect on disease severity and the risk for Psoriatic arthritis (PsA).

Methods: Cross-sectional observational study of 580 psoriasis patients and 567 healthy controls who were genotyped for six single nucleotide polymorphisms (SNPs) in the IL17RA (rs4819554, rs879577), IL17A (rs7747909), IL17F (rs763780, rs2397084), and IL17E (rs79877597) genes.

The Cw6 and late-cornified envelope genotype plays a significant role in anti-tumor necrosis factor response among psoriatic patients.

Our aim was to determine whether the HLA-Cw6 and late-cornified envelope (LCE) deletion polymorphisms were related to disease improvement among psoriasis patients treated with anti-tumor necrosis factor (TNF) antibodies. The study included a total of 116 patients. Positive response (68%) was defined as a reduction of at least 75% of the Psoriasis Area and Severity Index (PASI) after 24 weeks of starting the anti-TNF therapy.