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The need for prognosticators in rheumatoid arthritis. Biological and clinical markers: where are we now?

Smolen JS, Aletaha D, Grisar J, Redlich K, Steiner G, Wagner O - Arthritis Res. Ther. (2008)

Bottom Line: It will be shown that the relationship of many biomarkers with disease characteristics is confounded by factors unrelated to the disease, and that only few biomarkers exist with some predictive value.Moreover, clinical markers appear of equal value as biomarkers for this purpose, although they likewise have limited capacity in these regards.The analysis suggests the search for better markers to predict outcomes and therapeutic responsiveness in rheumatoid arthritis needs to be intensified.

View Article: PubMed Central - HTML - PubMed

Affiliation: Division of Rheumatology, Department of Internal Medicine III, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria. josef.smolen@meduniwien.ac.at

ABSTRACT
Rheumatoid arthritis is a heterogeneous disease with respect to clinical manifestations, serologic abnormalities, joint damage and functional impairment. Predicting outcome in a reliable way to allow for strategic therapeutic decision-making as well as for prediction of the response to the various therapeutic modalities available today, especially biological agents, would provide means for optimization of care. In the present article, the current information on biological and clinical markers related to disease activity and joint damage as well as for predictive purposes is reviewed. It will be shown that the relationship of many biomarkers with disease characteristics is confounded by factors unrelated to the disease, and that only few biomarkers exist with some predictive value. Moreover, clinical markers appear of equal value as biomarkers for this purpose, although they likewise have limited capacity in these regards. The analysis suggests the search for better markers to predict outcomes and therapeutic responsiveness in rheumatoid arthritis needs to be intensified.

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Depiction of potential cytokine and cellular patterns in four hypothetical patients with rheumatoid arthritis. Upper panel: hypothetical biological activities of various cytokines. Lower panel: hypothetical biological activities of various cell types. y axis, arbitrary units of activity. For example, in patient #1 TNF does not appear bioactive, while in patient #3 B cells appear uninvolved. Especially in patient #4, however, all cytokines – and in patient #1 all cell types – appear actively engaged in the disease process. In patient #2 IL-6 may not be detectable. It is unclear to what extent which of those cells and/or cytokines is contributing and if one or several targeted therapies would be efficacious. Although such relationships have not yet been elucidated, differences in synovial cellular compositions and cytokine contents have been noted in various studies [55,59,99]. DC, dendritic cells; Fib, fibroblasts.
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Figure 2: Depiction of potential cytokine and cellular patterns in four hypothetical patients with rheumatoid arthritis. Upper panel: hypothetical biological activities of various cytokines. Lower panel: hypothetical biological activities of various cell types. y axis, arbitrary units of activity. For example, in patient #1 TNF does not appear bioactive, while in patient #3 B cells appear uninvolved. Especially in patient #4, however, all cytokines – and in patient #1 all cell types – appear actively engaged in the disease process. In patient #2 IL-6 may not be detectable. It is unclear to what extent which of those cells and/or cytokines is contributing and if one or several targeted therapies would be efficacious. Although such relationships have not yet been elucidated, differences in synovial cellular compositions and cytokine contents have been noted in various studies [55,59,99]. DC, dendritic cells; Fib, fibroblasts.

Mentions: To better appreciate the complexity, we present four hypothetical patients in whom different cytokines or different cell populations may appear to predominate, even though in all patients many cells or soluble molecules are at least partly activated (Figure 2).


The need for prognosticators in rheumatoid arthritis. Biological and clinical markers: where are we now?

Smolen JS, Aletaha D, Grisar J, Redlich K, Steiner G, Wagner O - Arthritis Res. Ther. (2008)

Depiction of potential cytokine and cellular patterns in four hypothetical patients with rheumatoid arthritis. Upper panel: hypothetical biological activities of various cytokines. Lower panel: hypothetical biological activities of various cell types. y axis, arbitrary units of activity. For example, in patient #1 TNF does not appear bioactive, while in patient #3 B cells appear uninvolved. Especially in patient #4, however, all cytokines – and in patient #1 all cell types – appear actively engaged in the disease process. In patient #2 IL-6 may not be detectable. It is unclear to what extent which of those cells and/or cytokines is contributing and if one or several targeted therapies would be efficacious. Although such relationships have not yet been elucidated, differences in synovial cellular compositions and cytokine contents have been noted in various studies [55,59,99]. DC, dendritic cells; Fib, fibroblasts.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2483438&req=5

Figure 2: Depiction of potential cytokine and cellular patterns in four hypothetical patients with rheumatoid arthritis. Upper panel: hypothetical biological activities of various cytokines. Lower panel: hypothetical biological activities of various cell types. y axis, arbitrary units of activity. For example, in patient #1 TNF does not appear bioactive, while in patient #3 B cells appear uninvolved. Especially in patient #4, however, all cytokines – and in patient #1 all cell types – appear actively engaged in the disease process. In patient #2 IL-6 may not be detectable. It is unclear to what extent which of those cells and/or cytokines is contributing and if one or several targeted therapies would be efficacious. Although such relationships have not yet been elucidated, differences in synovial cellular compositions and cytokine contents have been noted in various studies [55,59,99]. DC, dendritic cells; Fib, fibroblasts.
Mentions: To better appreciate the complexity, we present four hypothetical patients in whom different cytokines or different cell populations may appear to predominate, even though in all patients many cells or soluble molecules are at least partly activated (Figure 2).

Bottom Line: It will be shown that the relationship of many biomarkers with disease characteristics is confounded by factors unrelated to the disease, and that only few biomarkers exist with some predictive value.Moreover, clinical markers appear of equal value as biomarkers for this purpose, although they likewise have limited capacity in these regards.The analysis suggests the search for better markers to predict outcomes and therapeutic responsiveness in rheumatoid arthritis needs to be intensified.

View Article: PubMed Central - HTML - PubMed

Affiliation: Division of Rheumatology, Department of Internal Medicine III, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria. josef.smolen@meduniwien.ac.at

ABSTRACT
Rheumatoid arthritis is a heterogeneous disease with respect to clinical manifestations, serologic abnormalities, joint damage and functional impairment. Predicting outcome in a reliable way to allow for strategic therapeutic decision-making as well as for prediction of the response to the various therapeutic modalities available today, especially biological agents, would provide means for optimization of care. In the present article, the current information on biological and clinical markers related to disease activity and joint damage as well as for predictive purposes is reviewed. It will be shown that the relationship of many biomarkers with disease characteristics is confounded by factors unrelated to the disease, and that only few biomarkers exist with some predictive value. Moreover, clinical markers appear of equal value as biomarkers for this purpose, although they likewise have limited capacity in these regards. The analysis suggests the search for better markers to predict outcomes and therapeutic responsiveness in rheumatoid arthritis needs to be intensified.

Show MeSH
Related in: MedlinePlus