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type=\u0022text\/css\u0022 rel=\u0022stylesheet\u0022 href=\u0022\/\/d282kpwvnogo5m.cloudfront.net\/sites\/default\/files\/cdn\/css\/http\/css_Xg7z6oCTVgud_Q0huYz9x9iiD5H_2YPSJ5z2ZViSWdY.css\u0022 media=\u0022all\u0022 \/\u003E\n\u003Clink rel=\u0027stylesheet\u0027 type=\u0027text\/css\u0027 href=\u0027\/sites\/all\/modules\/contrib\/panels\/plugins\/layouts\/onecol\/onecol.css\u0027 \/\u003E\u003C\/head\u003E\u003Cbody\u003E\u003Cdiv class=\u0022panels-ajax-tab-panel panels-ajax-tab-panel-sageoa-tab-art\u0022\u003E\u003Cdiv class=\u0022panel-display panel-1col clearfix\u0022 \u003E\n  \u003Cdiv class=\u0022panel-panel panel-col\u0022\u003E\n    \u003Cdiv\u003E\u003Cdiv class=\u0022panel-pane pane-highwire-markup\u0022 \u003E\n  \n      \n  \n  \u003Cdiv class=\u0022pane-content\u0022\u003E\n    \u003Cdiv class=\u0022highwire-markup\u0022\u003E\u003Cdiv xmlns=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022 id=\u0022content-block-markup\u0022 xmlns:xhtml=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022\u003E\u003Cdiv class=\u0022article fulltext-view \u0022\u003E\u003Cspan class=\u0022highwire-journal-article-marker-start\u0022\u003E\u003C\/span\u003E\u003Cdiv class=\u0022section abstract\u0022 id=\u0022abstract-1\u0022\u003E\u003Ch2\u003ESummary\u003C\/h2\u003E\n            \u003Cp id=\u0022p-1\u0022\u003EThis article discusses the latest advances concerning genes and the environment, and their impact on the development of rheumatoid arthritis (RA). Other topics include the need for new treatment strategies for early RA, and results from the RAPID 1 trial and FIN-RACo study, among other things.\u003C\/p\u003E\n         \u003C\/div\u003E\u003Cdiv class=\u0022section\u0022 id=\u0022sec-1\u0022\u003E\n         \n         \u003Cp id=\u0022p-2\u0022\u003ELars Klareskog, MD, Karolinska Institute, Stockholm, updated EULAR attendees on the latest advances concerning genes and the environment, and their impact on the development of rheumatoid arthritis (RA). \u201cRA is a heterogeneous syndrome whose etiology and pathogenesis can be defined by subphenotypes\u201d, said Prof. Klareskog.\u003C\/p\u003E\n         \u003Cp id=\u0022p-3\u0022\u003EIn a recent study, smoking (an environmental factor), in the context of HLA-DR shared epitope genes, was identified as a possible trigger for RA-specific immune reactions to citrullinated proteins. Since antibodies against citrullinated proteins are specific and predictive markers for RA, Prof. Klareskog suggested that an etiology involving a definite genotype, an environmental provocation, and the induction of specific autoimmunity, impacts the development of a distinct subset of RA [Klareskog L et al. Arthritis Rheum 2006].\u003C\/p\u003E\n         \u003Cp id=\u0022p-4\u0022\u003EProf. Klareskog believes that information of this nature will lead to the use of genetic epidemiology as a basis for studies on the molecular pathology of RA, possibly resulting in a new taxonomy built on these different molecular pathologies. New therapies may then be based on the different molecular pathologies that cause RA and tailored to the individual.\u003C\/p\u003E\n         \u003Cp id=\u0022p-5\u0022\u003EThe current goals of RA therapy are to produce remission, halt and heal disease related destruction, reverse disability and return the patient to a normal life expectancy. To do this however, therapy needs to be optimized and more information is required to understand the response to treatment of the individual patient. To this end, \u201cnew clinical and biological markers are needed that can predict those patients most likely to respond to a particular treatment\u201d, stated Josef S. Smolen, MD, Medical University of Vienna.\u003C\/p\u003E\n         \u003Cp id=\u0022p-6\u0022\u003ENew markers such as the cartilage oligometrix matrix protein (COMP), a glycoprotein, are being tested as possible identifiers of joint damage. However, inheritable factors, diurnal variation, and degrees of progression influence serum levels of COMP and can compromise the usefulness of this and other marker.\u003C\/p\u003E\n         \u003Cp id=\u0022p-7\u0022\u003EEffective therapy, such as with prednisolone, is associated with a marked reduction in macrophage infiltration in RA synovial tissue, suggesting that the number of synovial macrophages could be used as a biomarker for clinical efficacy [Gerlag DM et al. \u003Cem\u003EArthritis Rheum\u003C\/em\u003E 2004]. However, the usefulness of this biomarker, which requires an invasive procedure, still needs to be validated based on demonstrated superiority to markers using other sources, such as serum or clinical markers.\u003C\/p\u003E\n         \u003Cp id=\u0022p-8\u0022\u003EHigh titer rheumatoid factor and anti-CCP, and especially C-reactive protein (CRP), continue to be the most reliable biomarkers for predicting joint damage. However, a highly reliable predictor for future disease activity are composite disease activity indices. At 3 months from start of treatment, the score of the simplified disease activity index was highly predictive of disease activity at one year. Nevertheless, additional prediction models may be needed to optimize therapy decisions. The combination of clinical and biological markers may allow for RA prediction for the effects of targeted therapies on the level of the individual patient.\u003C\/p\u003E\n         \u003Cp id=\u0022p-9\u0022\u003EGiven our improved understanding of the causes and detection of RA, Thomas Huizinga, MD, Leiden University Medical Center, The Netherlands, addressed the need for new treatment strategies for early RA. He empathized that RA should be diagnosed and treated with disease-modifying anti-rheumatic drugs (DMARDs) as early as possible. Delay of DMARD therapy has been shown to be a major contributing factor to poor outcome. There is a window of opportunity for highly successful RA treatment in the first year, and especially within the first 3 months of diagnoses [Nell VP et al. \u003Cem\u003ERheumatology\u003C\/em\u003E 2004].\u003C\/p\u003E\n         \u003Cp id=\u0022p-10\u0022\u003EResults of the PROMPT study have shown that immediate treatment with MTX retards damage. Undifferentiated arthritis progressed to RA in 40% of the MTX treated patients vs 53% of patients in the placebo group. However, in the MTX group, a significant (p=0.046) time delay for patients fulfilling the ACR criteria for RA was noted compared with the placebo group. In addition, significantly (p=0.046) fewer patients showed radiographic progression (p\u0026lt; 0.05) suggesting that early treatment with MTX delayed the progression of RA [van Dongen H et al. \u003Cem\u003EArthritis Rheum\u003C\/em\u003E 2007].\u003C\/p\u003E\n         \u003Cp id=\u0022p-11\u0022\u003EGrigor and colleagues have shown that a strategy of intensive outpatient management of RA, as opposed to routine outpatient care, substantially improves disease activity, radiographic disease progression, physical function, and quality of life at no additional cost [Grigor C et al. Lancet 2004]. Prof. Huizinga believes that there is utility in monotherapy, but combination therapy is better. The major challenge is differentiating between patients who should receive MTX monotherapy versus those who should receive combination therapy at disease onset.\u003C\/p\u003E\n         \u003Cp id=\u0022p-12\u0022\u003EThe RAPID 1 phase 3 study results, presented by Edward C. Keystone, MD, University of Toronto, reported on the efficacy and tolerability of two dose regimens of certolizumab pegol, the first PEGylated anti-TNF to be studied as add-on therapy in patients with active RA who are refractory to MTX monotherapy. Patients, previously treated for \u22656 months with MTX, were treated with certolizumab pegol, three 400 mg doses every 2 weeks or placebo, followed by certolizumab pegol (200 mg or 400 mg) every 2 weeks, or placebo. MTX therapy was continued as usual. At week 24, the ACR20 response was 59.2% in the certolizumab pegol 200 mg group, 61.2% in the 400 mg group, and 13.5% in the placebo group (MTX alone) (p\u0026lt;0.001 active vs placebo). Significant differences from placebo (p\u0026lt;0.001) were also reported for the ACR50 and ACR70 endpoints.\u003C\/p\u003E\n         \u003Cp id=\u0022p-13\u0022\u003EThe majority of adverse events were mild to moderate. Prof. Keystone commented, \u201cwhen treatment with MTX as a monotherapy does not achieve sufficient results, we have shown that adding certolizumab pegol can achieve significant improvement in symptoms.\u201d\u003C\/p\u003E\n         \u003Cp id=\u0022p-14\u0022\u003EVappu Rantalaiho, MD, Tampere University Hospital, Finland, presented results of the FIN-RACo study which evaluated the long-term frequency of remission and change in HAQ values over the course of 11 years in patients with early RA initially treated either with a combination of 3 DMARDs or a single DMARD for 2 years. The estimated remission rate over time was 32% in the combination group and 19% in the single group (p=0.0082; \u003Ca id=\u0022xref-fig-1-1\u0022 class=\u0022xref-fig\u0022 href=\u0022#F1\u0022\u003EFigure 1\u003C\/a\u003E). The mean improvement in HAQ was not significantly different between the two groups. In the combination group, remission at 6 months was a strong predictor of remission at 11 years \u2013 emphasizing the importance of early and aggressive DMARD therapy in RA.\u003C\/p\u003E\n         \u003Cdiv id=\u0022F1\u0022 class=\u0022fig pos-float  odd\u0022\u003E\u003Cdiv class=\u0022highwire-figure\u0022\u003E\u003Cdiv class=\u0022fig-inline-img-wrapper\u0022\u003E\u003Cdiv class=\u0022fig-inline-img\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/7\/4\/22\/F1.large.jpg?width=800\u0026amp;height=600\u0026amp;carousel=1\u0022 title=\u0022Remission Rates Over Time: Combination vs Single Therapy.\u0022 class=\u0022fragment-images colorbox-load\u0022 rel=\u0022gallery-fragment-images-1745188181\u0022 data-figure-caption=\u0022Remission Rates Over Time: Combination vs Single Therapy.\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003E\u003Cimg class=\u0022fragment-image\u0022 alt=\u0022Figure 1.\u0022 src=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/7\/4\/22\/F1.medium.gif\u0022\/\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cul class=\u0022highwire-figure-links inline\u0022\u003E\u003Cli class=\u00220 first\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/7\/4\/22\/F1.large.jpg?download=true\u0022 class=\u0022highwire-figure-link highwire-figure-link-download\u0022 title=\u0022Download Figure 1.\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload figure\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00221\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/7\/4\/22\/F1.large.jpg\u0022 class=\u0022highwire-figure-link highwire-figure-link-newtab\u0022 target=\u0022_blank\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EOpen in new tab\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00222 last\u0022\u003E\u003Ca href=\u0022\/highwire\/powerpoint\/11161\u0022 class=\u0022highwire-figure-link highwire-figure-link-ppt\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload powerpoint\u003C\/a\u003E\u003C\/li\u003E\u003C\/ul\u003E\u003C\/div\u003E\u003Cdiv class=\u0022fig-caption\u0022 xmlns:xhtml=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022\u003E\u003Cspan class=\u0022fig-label\u0022\u003EFigure 1.\u003C\/span\u003E \n               \u003Cp id=\u0022p-15\u0022 class=\u0022first-child\u0022\u003ERemission Rates Over Time: Combination vs Single Therapy.\u003C\/p\u003E\n            \u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\n         \u003Cp id=\u0022p-16\u0022\u003EIn a phase 2 trial, ofatumumab (HuMax-CD20), a human monoclonal anti-CD20 IgG1 antibody, was administered to patients with active RA. Mikkel \u00d8tergaard, MD, Copenhagen University Hospital, Denmark, reported that a significantly increased proportion of patients receiving 2 infusions of ofatumumab (300 mg, 700 mg or 1000 mg) obtained an ACR20 response at week 24 (41% [p=0.002], 49% [p\u0026lt;0.001] and 46% [p\u0026lt;0.001], respectively) vs patients receiving placebo (15%). Likewise, significantly more patients had good or moderate EULAR responses after treatment with ofatumumab (72% in each dose group) vs placebo (40%; p=0.001).\u003C\/p\u003E\n         \u003Cp id=\u0022p-17\u0022\u003EOfatumumab was generally well tolerated and all patients tested negative for human anti-human antibodies. Rapid and sustained peripheral CD19+ B-cell depletion was observed in all ofatumumab dose groups. This first analysis of data from an ongoing trial shows encouraging results of ofatumumab therapy in patients with RA.\u003C\/p\u003E\n      \u003C\/div\u003E\u003Cul class=\u0022copyright-statement\u0022\u003E\u003Cli class=\u0022fn\u0022 id=\u0022copyright-statement-1\u0022\u003E\u00a9 2007 MD Conference Express\u003C\/li\u003E\u003C\/ul\u003E\u003Cspan class=\u0022highwire-journal-article-marker-end\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Cspan id=\u0022related-urls\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Ca href=\u0022http:\/\/mdc.sagepub.com\/content\/7\/4\/22.abstract\u0022 class=\u0022hw-link hw-link-article-abstract\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView Summary\u003C\/a\u003E\u003C\/div\u003E  \u003C\/div\u003E\n\n  \n  \u003C\/div\u003E\n\u003C\/div\u003E\n  \u003C\/div\u003E\n\u003C\/div\u003E\n\u003C\/div\u003E\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_figures.js?nzm9q1\u0022\u003E\u003C\/script\u003E\n\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_openurl.js?nzm9q1\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}