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Genovese M.C.,Stanford University | Bojin S.,County Hospital | Biagini I.M.,County Hospital | Mociran E.,County Hospital | And 4 more authors.
Arthritis and Rheumatism | Year: 2013

Objective Tabalumab, a fully human IgG4 monoclonal antibody, neutralizes soluble and membrane-bound BAFF. The aim of this study was to examine the tolerability and efficacy of tabalumab in patients with active rheumatoid arthritis receiving methotrexate. Methods In this randomized, double-blind, placebo-controlled, parallel, multiple-dose study, patients who were naive to biologic therapy received infusions of tabalumab (30, 60, or 160 mg) or placebo at weeks 0, 3, and 6 in combination with methotrexate and were evaluated for 24 weeks. The primary efficacy end point was the percentage of patients meeting American College of Rheumatology 20% improvement criteria (achieving an ACR20 response) at week 16. Results At week 16, the percentages of patients achieving an ACR20 response in the 30-mg (57.6%), 60-mg (67.6%), and 160-mg (51.5%) groups were significantly greater than the percentage of patients achieving an ACR20 response in the placebo group (29.4%; P < 0.05). There were initial transient increases from baseline in the frequency of CD20+ and IgD+/CD27- B cells, followed by reductions, although B cells were not completely depleted. Also, the frequency of IgD-/CD27+ B cells increased in all tabalumab groups compared with the placebo group and returned toward baseline levels by the end of the study. The incidence of adverse events was similar across all treatment groups; no deaths occurred. Serum IgM levels decreased significantly in all tabalumab groups combined compared with the placebo group. There were no significant decreases in serum IgG or IgA levels in the tabalumab groups compared with the placebo group. Conclusion Tabalumab treatment significantly reduces the signs and symptoms of rheumatoid arthritis and has a safety profile similar to that seen with placebo treatment. Copyright © 2013 by the American College of Rheumatology. Source

Gamazon E.R.,University of Chicago | Gamazon E.R.,Vanderbilt University | Wheeler H.E.,University of Chicago | Shah K.P.,University of Chicago | And 9 more authors.
Nature Genetics | Year: 2015

Genome-wide association studies (GWAS) have identified thousands of variants robustly associated with complex traits. However, the biological mechanisms underlying these associations are, in general, not well understood. We propose a gene-based association method called PrediXcan that directly tests the molecular mechanisms through which genetic variation affects phenotype. The approach estimates the component of gene expression determined by an individual's genetic profile and correlates 'imputed' gene expression with the phenotype under investigation to identify genes involved in the etiology of the phenotype. Genetically regulated gene expression is estimated using whole-genome tissue-dependent prediction models trained with reference transcriptome data sets. PrediXcan enjoys the benefits of gene-based approaches such as reduced multiple-testing burden and a principled approach to the design of follow-up experiments. Our results demonstrate that PrediXcan can detect known and new genes associated with disease traits and provide insights into the mechanism of these associations. © 2015 Nature America, Inc. All rights reserved. Source

Ravelli A.,University of Genoa | Ravelli A.,Rheumatology Center
Handbook of Juvenile Idiopathic Arthritis | Year: 2016

This handbook is an in-depth and comprehensive guide for the treatment and management of patients with juvenile idiopathic arthritis. The handbook provides an informative review of the disease looking at the epidemiology, etiology and pathogenesis, issues of diagnosis and classification, consequences and complications, general treatment aspects, as well as both non pharmacologic and pharmacologic therapy whilst considering the future outlook for patients with juvenile idiopathic arthritis. Juvenile idiopathic arthritis is the most common type of arthritis found in children and adolescents, affecting about 1 in 1,000 children. It is a chronic disease which causes inflammation, pain and swelling of the affected joints and can affect joints in any part of the body. This Handbook provides an unbiased, informative discussion of the current and emerging treatments in this field. © Springer International Publishing Switzerland 2016. Source

Rouzaud M.,Bordeaux University Hospital Center | Sevrain M.,Brest University Hospital Center | Villani A.P.,University of Lyon | Barnetche T.,Bordeaux University Hospital Center | And 11 more authors.
Journal of the European Academy of Dermatology and Venereology | Year: 2014

Psoriatic arthritis (PsA) is associated with psoriasis with a prevalence varying from 5.94% to 23.9%. The aim of this study was to assess if some psoriatic skin features are associated with a higher risk of PsA. A systematic literature search was carried out from 1980 to January 2013, in the Embase and Pubmed databases, using a combination of keywords including (Psoriasis) AND (PsA). Of the 2746 articles retrieved, 25 references were selected. Meta-analysis was performed when possible. Mean age at psoriasis onset appeared to be similar among patients with skin disease alone and in those with PsA. There was no clinical type of psoriasis specifically associated with PsA, including pustular psoriasis of palms and soles. Nonetheless specific psoriasis localizations were significantly associated with an increased risk of developing PsA in one cohort study: scalp lesions [Hazard Ratio (HR) 3.89 (95% confidence interval (CI):2.18-6.94)] and intergluteal/perianal lesions [HR 2.35 (95%CI:1.32-4.19)]. A similar association was found in two cross-sectional studies. Nail involvement was significantly associated with PsA in the meta-analysis [Odds Ratio (OR) 2.92 (95% CI 2.34-3.64)], particularly onycholysis [OR 2.38 (95% CI 1.74-3.26)]. Moreover, nail psoriasis was also associated with distal interphalangeal joint arthritis. The extent of psoriasis appeared to be associated with PsA in one cohort study [≥3 sites: HR 2.24 (95% CI 1.23-4.08)], one case-control study [body surface area >75%: OR 2.52 (95% CI 1.33-4.75)] and three cross-sectional studies. The meta-analysis suggested a trend for an association between high PASI and PsA risk [mean difference 3.39 (95% CI 0.94-5.83)]. Therefore, psoriasis patients with such clinical features may require a particular attention for early and close detection of PsA during the course of the cutaneous disease. © 2014 European Academy of Dermatology and Venereology. Source

Richard M.-A.,Aix - Marseille University | Barnetche T.,Bordeaux University Hospital Center | Rouzaud M.,Bordeaux University Hospital Center | Sevrain M.,Brest University Hospital Center | And 11 more authors.
Journal of the European Academy of Dermatology and Venereology | Year: 2014

Background Psoriatic arthritis (PsA) can develop at any time during the course of psoriasis. Aims The aims of these practical recommendations are to help dermatologists identify patients at risk of PsA, to diagnose PsA in collaboration with rheumatologists and to gain a better understanding of initial PsA management. Materials and methods A scientific committee consisting of 10 dermatologists and a rheumatologist selected clinically relevant questions to be addressed by evidence-based recommendations using the DELPHI method. For each question, a systematic literature review was performed in Medline, Embase and the Cochrane Library databases. The levels of evidence of all selected and reviewed articles were appraised according to the Oxford levels of evidence. Results An expert board of 30 dermatologists reviewed and analysed the evidence and developed recommendations for the selected questions. Agreement among participants was assessed on a 10-point scale, and the potential impact of the recommendations on clinical practice was evaluated. Among the 6960 references identified, 190 relevant articles were included in the reviews. Three recommendations regarding risk factors for PsA and one regarding PsA prevalence were issued. The mean agreement score between participants varied from 7.8 to 9.6. Three recommendations on PsA screening tools that can be used by dermatologists were issued. The mean agreement score between participants varied from 7.7 to 9.4. Initial PsA treatment options according to published guidelines were critically appraised for axial and peripheral involvement and enthesitis/dactylitis. Three recommendations were issued. The mean agreement score between participants varied from 7.6 to 8.7. Discussion The systematic literature research and meta-analyses did not provide high-quality evidence to support recommendations regarding PsA screening. Conversely, PsA treatment options were supported by strong evidence. Conclusion Cooperation between dermatologists and rheumatologists should be emphasized to better identify and manage PsA patients. © 2014 European Academy of Dermatology and Venereology. Source

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