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type=\u0022text\/css\u0022 rel=\u0022stylesheet\u0022 href=\u0022\/\/d282kpwvnogo5m.cloudfront.net\/sites\/default\/files\/advagg_css\/css__ce2QY63WIanKyr8eSq7eavr1XQRRmFD6ZSmwpyJi8lM__zXwFqpqmxrZOXXcd_TpBQpjuELbmIP9wBR5UuTDWAO4__YJWWMMdfCJuAFm5cUEp88OsodhO3ZA-2lzRfoBsSlk4.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\u003EWhile progress has been made in predicting response to therapy for juvenile rheumatoid arthritis, major efforts are still needed in some areas before individualized treatment will be possible. This articles explores the current status of this topic for juvenile idiopathic arthritis, biomarker development, and cytokine blockade.\u003C\/p\u003E\n         \u003C\/div\u003E\u003Cul class=\u0022kwd-group\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003EInflammatory Disorders\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EArthritis\u003C\/li\u003E\u003C\/ul\u003E\u003Cul class=\u0022kwd-group clinical-trial\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003EInflammatory Disorders\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003ERheumatology\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EArthritis\u003C\/li\u003E\u003C\/ul\u003E\u003Cdiv class=\u0022section\u0022 id=\u0022sec-1\u0022\u003E\n         \n         \u003Cp id=\u0022p-2\u0022\u003EWhile progress has been made in predicting response to therapy for juvenile rheumatoid arthritis (JRA), major efforts are still needed in some areas before individualized treatment will be possible. This session explored the current status of this topic for juvenile idiopathic arthritis (JIA), biomarker development, and cytokine blockade.\u003C\/p\u003E\n      \u003C\/div\u003E\u003Cdiv class=\u0022section\u0022 id=\u0022sec-2\u0022\u003E\n         \u003Ch2 class=\u0022\u0022\u003EPREDICTION OF RESPONSE TO THERAPY: LESSONS FROM JIA\u003C\/h2\u003E\n         \u003Cp id=\u0022p-3\u0022\u003ENico Wulffraat, MD, PhD, University Medical Center, Utrecht, The Netherlands, spoke about the prediction of response to therapy for patients with JIA. Risk factors for poor treatment outcomes include female sex, polyarticular and symmetrical joint involvement, elevated inflammatory markers, and rheumatoid factor (RF) positivity [Adib N et al. \u003Cem\u003ERheumatology (Oxford)\u003C\/em\u003E 2005]. However, that research was conducted prior to the impact of treating JIA with biologic drugs, said Prof. Wulffraat.\u003C\/p\u003E\n         \u003Cp id=\u0022p-4\u0022\u003EAnother study suggested that the persistent oligoarticular JIA (pers-OA-JIA) subtype of JIA predicted a relatively benign, self-remitting path, while extended OA JIA (ext-OA-JIA) fared less favorably [de Kleer IM et al. \u003Cem\u003EJ Immunol\u003C\/em\u003E 2004]. Peripheral blood of patients with pers-OA-JIA had a significantly higher frequency of CD4\u003Csup\u003E+\u003C\/sup\u003ECD25\u003Csup\u003Ebright\u003C\/sup\u003E regulatory T cells and higher levels of mRNA FOXP3 than ext-OA-JIA patients. It may be that these regulatory T cells mature in the synovial fluids of the joint.\u003C\/p\u003E\n         \u003Cp id=\u0022p-5\u0022\u003EOther research found that starting treatment (methotrexate [MTX]) earlier after diagnosis can improve response at 6 months [Albers HM et al. \u003Cem\u003EArthritis Rheum\u003C\/em\u003E 2009] and that young patients (\u0026gt;3 years 6 months) who start treatment early with etanercept and do not have wrist involvement are more likely to achieve inactive disease status [Solari N et al. \u003Cem\u003EJ Rheumatol\u003C\/em\u003E 2013].\u003C\/p\u003E\n         \u003Cp id=\u0022p-6\u0022\u003EClinical measures taken soon after diagnosis may help with prediction of treatment response. A Canadian study found that the Juvenile Arthritis Quality of Life Questionnaire is a predictor of multiple outcomes [Oen K et al. \u003Cem\u003EArthritis Rheum\u003C\/em\u003E 2009]. A very recent study found that high levels of baseline MRP8\/14 (\u0026gt;3000 ng\/mL) predicted the subgroup of patients more likely to respond to MTX (\u003Ca id=\u0022xref-fig-1-1\u0022 class=\u0022xref-fig\u0022 href=\u0022#F1\u0022\u003EFigure 1\u003C\/a\u003E) [Moncrieffe H et al. \u003Cem\u003ERheumatology (Oxford)\u003C\/em\u003E 2013].\u003C\/p\u003E\n         \u003Cp id=\u0022p-7\u0022\u003EGenetics research has revealed polymorphisms associated with a positive clinical response to MTX and produced a model to predict outcome. One study showed a positive association with polymorphisms in the AMPD1, ATIC, and ITPA genes [Wessels JA et al. \u003Cem\u003EArthritis Rheum\u003C\/em\u003E 2006]. In other work, Prof. Wulffraat and colleagues described a model they developed and validated that can identify nonresponders through clinical and genetic variables [Bulatovic M et al. \u003Cem\u003EAnn Rheum Dis\u003C\/em\u003E 2012].\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\/13\/8\/16\/F1.large.jpg?width=800\u0026amp;height=600\u0026amp;carousel=1\u0022 title=\u0022Myeloid-Related Protein May Predict Response\u0022 class=\u0022fragment-images colorbox-load\u0022 rel=\u0022gallery-fragment-images-1798803130\u0022 data-figure-caption=\u0022Myeloid-Related Protein May Predict Response\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\/13\/8\/16\/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\/13\/8\/16\/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\/13\/8\/16\/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\/13387\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 attrib\u0022\u003E\u003Cspan class=\u0022fig-label\u0022\u003EFigure 1.\u003C\/span\u003E \n               \u003Cp id=\u0022p-8\u0022 class=\u0022first-child\u0022\u003EMyeloid-Related Protein May Predict Response\u003C\/p\u003E\n            \u003Cq class=\u0022attrib\u0022 id=\u0022attrib-1\u0022\u003EMTX=methotrexate.\u003C\/q\u003E\u003Cq class=\u0022attrib\u0022 id=\u0022attrib-2\u0022\u003EReproduced from Moncrieffe H et al. A subgroup of juvenile idiopathic arthritis patients who respond well to methotrexate are identified by the serum biomarker MRP8\/14 protein. \u003Cem\u003ERheumatology (Oxford)\u003C\/em\u003E 2013; 52(8):1467\u20131476. With permission from Oxford University Press.\u003C\/q\u003E\u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\n         \u003Cp id=\u0022p-9\u0022\u003EWhile prediction of response to therapy largely relies on subtype, disease duration, and disease activity, increasing biomarker development activity will hopefully improve individualized medicine, Prof. Wulffraat concluded.\u003C\/p\u003E\n      \u003C\/div\u003E\u003Cdiv class=\u0022section\u0022 id=\u0022sec-3\u0022\u003E\n         \u003Ch2 class=\u0022\u0022\u003EBIOMARKERS PREDICTING RELAPSES IN INFLAMMATORY ARTHRITIS\u003C\/h2\u003E\n         \u003Cp id=\u0022p-10\u0022\u003EDirk Foell, MD, University of M\u00fcnster, M\u00fcnster, Germany, expanded on the topic of biomarkers. Although drug-free remission can be achieved in 17% to 29% of patients and sustained in 9% to 16% during a 1- to 4-year period, low disease activity can be reached again in most patients who restart treatment [van den Broek M et al. \u003Cem\u003ECurr Opin Rheumatol\u003C\/em\u003E 2011]. However, patients with JIA often experience inactive and active episodes of disease over a course of 5 years [Wallace CA et al. \u003Cem\u003EArthritis Rheum\u003C\/em\u003E 2005].\u003C\/p\u003E\n         \u003Cp id=\u0022p-11\u0022\u003EPower Doppler ultrasound has proven beneficial in predicting relapse and remission responses. A recent study found that ultrasound-detected abnormalities may be common in children with JIA in remission, but it does not predict early flare [Magni-Manzoni S et al. \u003Cem\u003EAnn Rheum Dis\u003C\/em\u003E 2012]. An earlier study found that for patients with RA in remission or with low disease activity, ultrasound could predict relapse or radiographic progression and predict adequately controlled disease in patients [Foltz V et al. \u003Cem\u003EArthritis Rheum\u003C\/em\u003E 2012].\u003C\/p\u003E\n         \u003Cp id=\u0022p-12\u0022\u003ETo better reach the goal of remission, Prof. Foell said, researchers need to define remission, which has been subject to ever-changing criteria [van den Broek M et al. \u003Cem\u003ECurr Opin Rheumatol\u003C\/em\u003E 2011]. While defining remission is based mainly on clinical manifestations of disease, additional criteria have been added since the preliminary definition of disease improvement in 1997 by the American College of Rheumatology [Ringold S, Wallace CA. \u003Cem\u003ECurr Opin Rheumatol\u003C\/em\u003E 2007]. Biomarkers, such as erythrocyte sedimentation rate and C-reactive protein (CRP) have been included for a long time.\u003C\/p\u003E\n         \u003Cp id=\u0022p-13\u0022\u003EMore studies have focused on biomarkers. One study identified MRP8\/14 complexes as new inflammatory components that activate phagocytes for protective effects [Vogl T et al. \u003Cem\u003ENat Med\u003C\/em\u003E 2007]. Another study showed that normal serum levels of MRP8\/14 in patients with clinically inactive JIA may predict that MTX treatment can be safely withdrawn after remission [Foell D et al. \u003Cem\u003EAnn Rheum Dis\u003C\/em\u003E 2004].\u003C\/p\u003E\n         \u003Cp id=\u0022p-14\u0022\u003EAnother study suggests a possible role for S100A12 in synovitis and points to high serum concentrations of the same protein as a useful serum marker in patients with active arthritis in remission (\u003Ca id=\u0022xref-fig-2-1\u0022 class=\u0022xref-fig\u0022 href=\u0022#F2\u0022\u003EFigure 2\u003C\/a\u003E) [Foell D et al. \u003Cem\u003ERheumatol\u003C\/em\u003Eogy (Oxford) 2003]. A recent study demonstrated that a combination of S100A12 and high-sensitivity CRP has at present the best predictive power for the risk of a disease relapse out of a status of instable clinical remission [Gerss J et al. \u003Cem\u003EAnn Rheum Dis\u003C\/em\u003E 2012]. A strategy for the stratification of patients for maintenance therapy versus withdrawal of anti-inflammatory drugs in times of disease remission has been proposed and a prospective trial applying this strategy for personalized medicine is under way.\u003C\/p\u003E\n         \u003Cdiv id=\u0022F2\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\/13\/8\/16\/F2.large.jpg?width=800\u0026amp;height=600\u0026amp;carousel=1\u0022 title=\u0022Biomarkers for the Risk of Relapse After Stopping Therapy\u0022 class=\u0022fragment-images colorbox-load\u0022 rel=\u0022gallery-fragment-images-1798803130\u0022 data-figure-caption=\u0022Biomarkers for the Risk of Relapse After Stopping Therapy\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003E\u003Cimg class=\u0022fragment-image\u0022 alt=\u0022Figure 2.\u0022 src=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/13\/8\/16\/F2.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\/13\/8\/16\/F2.large.jpg?download=true\u0022 class=\u0022highwire-figure-link highwire-figure-link-download\u0022 title=\u0022Download Figure 2.\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\/13\/8\/16\/F2.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\/13388\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 attrib\u0022\u003E\u003Cspan class=\u0022fig-label\u0022\u003EFigure 2.\u003C\/span\u003E \n               \u003Cp id=\u0022p-15\u0022 class=\u0022first-child\u0022\u003EBiomarkers for the Risk of Relapse After Stopping Therapy\u003C\/p\u003E\n            \u003Cq class=\u0022attrib\u0022 id=\u0022attrib-3\u0022\u003EhsCRP=high-sensitivity C=reactive protein.\u003C\/q\u003E\u003Cq class=\u0022attrib\u0022 id=\u0022attrib-4\u0022\u003EReproduced with permission from D Foell, MD.\u003C\/q\u003E\u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\n         \u003Cp id=\u0022p-16\u0022\u003ERemission can be reached by children with JIA and adults with RA. The full potential of imaging modalities and biomarkers has not been defined. Yet, S100 biomarkers indicate subclinical inflammation, which may help to identify patients with increased risk of flares and allow stratification of patients for therapeutic decision-making.\u003C\/p\u003E\n      \u003C\/div\u003E\u003Cdiv class=\u0022section\u0022 id=\u0022sec-4\u0022\u003E\n         \u003Ch2 class=\u0022\u0022\u003ENEW STRATEGIES TO PREDICT RESPONSE TO CYTOKINE BLOCKADE\u003C\/h2\u003E\n         \u003Cp id=\u0022p-17\u0022\u003EGeorg Schett, MD, University of Erlangen-Nuremberg, Erlangen, Germany, reviewed the need for better understanding cytokines and tumor necrosis factor (TNF) blockers. A TNF inhibitor (TNFi) can achieve a moderate to good response (EULAR criteria) in about half of RA patients, but to date no reliable predictor of treatment response has been identified. Blocking TNF, which induces hyperalgesia associated with higher neuronal activity in central nervous system areas involved in pain perception, can block activation of the pain pathway in mice and humans.\u003C\/p\u003E\n         \u003Cp id=\u0022p-18\u0022\u003EThe most widely used tool for detecting brain activity is functional magnetic resonance iomaging (fMRI). Schett and colleagues demonstrated on fMRI that blocking TNF-\u03b1 produced a positive response in the thalamus and somatsensoric cortex within 24 hours of administration of a monoclonal antibody to TNF-\u03b1 [Hess A et al. \u003Cem\u003EProc Natl Acad Sci USA\u003C\/em\u003E 2011]. Their results also showed that the response in the brain preceded any response in the joints, which suggests that joint compression also induces activity in the limbic system, relevant for inner body sensation.\u003C\/p\u003E\n         \u003Cp id=\u0022p-19\u0022\u003ESchett and colleagues then used fMRI to assess activity in the brain and hand and to conduct a clinical assessment in 10 patients with RA before and 3, 7, and 28 days after the start of TNFi treatment. While responders showed significantly higher activity in the thalamic, limbic, and associated brain areas (\u003Ca id=\u0022xref-fig-3-1\u0022 class=\u0022xref-fig\u0022 href=\u0022#F3\u0022\u003EFigure 3\u003C\/a\u003E), brain activity decreased within 3 days after exposure, which preceded clinical responses on Day 7 and MRI-observed hand responses on Day 28.\u003C\/p\u003E\n         \u003Cp id=\u0022p-20\u0022\u003EThe PRECAPRA trial will evaluate whether high fMRI activity can predict response to therapy with a TNFi. The Phase 3 multicenter, randomized controlled trial will compare certolizumab and placebo in 52 patients.\u003C\/p\u003E\n         \u003Cdiv id=\u0022F3\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\/13\/8\/16\/F3.large.jpg?width=800\u0026amp;height=600\u0026amp;carousel=1\u0022 title=\u0022TNF Blockade Affects Normal Brain Activity\u0022 class=\u0022fragment-images colorbox-load\u0022 rel=\u0022gallery-fragment-images-1798803130\u0022 data-figure-caption=\u0022TNF Blockade Affects Normal Brain Activity\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003E\u003Cimg class=\u0022fragment-image\u0022 alt=\u0022Figure 3.\u0022 src=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/13\/8\/16\/F3.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\/13\/8\/16\/F3.large.jpg?download=true\u0022 class=\u0022highwire-figure-link highwire-figure-link-download\u0022 title=\u0022Download Figure 3.\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\/13\/8\/16\/F3.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\/13391\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 attrib\u0022\u003E\u003Cspan class=\u0022fig-label\u0022\u003EFigure 3.\u003C\/span\u003E \n               \u003Cp id=\u0022p-21\u0022 class=\u0022first-child\u0022\u003ETNF Blockade Affects Normal Brain Activity\u003C\/p\u003E\n            \u003Cq class=\u0022attrib\u0022 id=\u0022attrib-5\u0022\u003EBOLD=blood-oxygen level-dependent; IFX=infliximab; TNFtg=tumor necrosis factor transgenic; WT=wild-type.\u003C\/q\u003E\u003Cq class=\u0022attrib\u0022 id=\u0022attrib-6\u0022\u003EReproduced with permission from G Schett, MD.\u003C\/q\u003E\u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\n      \u003C\/div\u003E\u003Cul class=\u0022copyright-statement\u0022\u003E\u003Cli class=\u0022fn\u0022 id=\u0022copyright-statement-1\u0022\u003E\u00a9 2013 MD Conference Express\u00ae\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\/13\/8\/16.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?nznsg1\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?nznsg1\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}