Figure 1.

Current and desired disease progression models. (A) Current “Trial-and-error” model: Upon diagnosis the first line of treatment is started, which may lead to remission, or partial remission. Often, a second, third or fourth treatment strategy needs to be implemented when the previous treatments are not effective. Choice of treatments is guided by previous experience, e.g., upon presentation non-steroidal anti-inflammatory drugs with glucocorticoids are used, after a couple of month many patients are switched to methotrexate as first disease modifying therapy, often followed by anti-TNF-α agents with/without methotrexate (4). This disease progression and subsequent staggering of therapy can result in irreversible damage and long-term therapy. (B) Desired personalized/biomarker-driven model: Biomarkers could be used for prediction and aid decisions at the following stages: disease trajectory, selection of treatment, early response to therapy, remission/minimal disease activity and the risk of flare upon withdrawal of therapy, ongoing monitoring of immune activity and risk of flares. Biomarkers might thus contribute to more efficient therapy, pre-empt flares, and minimize short- and long-term effects of flares and reduce long-term damage. Lines represent models of disease progression, with line thickness representing frequency estimates.