Cohort studies from recent years have demonstrated that shifting from one disease phenotype to another is frequent during the life course of patients. In one landmark study it was shown that up to 80% of the patients will suffer from a stricturing or penetrating complication over 20 years of follow-up.5 The observation of changing disease patterns and accumulation of tissue Inhibitors,research,lifescience,medical damage over time suggests that it may be the result of repeated inflammatory activity during flares and hence potentially preventable by administration of appropriate treatment. Although straightforward, this simple logic is difficult to practice when reduced to practical

cost–benefit terms, both from the patients’ well-being and actual cost perspectives. Implementation Inhibitors,research,lifescience,medical of successful preventive treatment would have to provide effective therapy and assure that side effects and cost are in proportion to clinical efficacy. Establishing such treatment strategy necessitates tools that allow quantification of tissue damage, scaling

and quantifying treatment side effects, and, most importantly, delivering care to those who are most likely to benefit from it. The last-mentioned point requires identification of predictive Inhibitors,research,lifescience,medical biomarkers to recognize not only patients who will suffer from a progressive disease course but also those who will respond to a given treatment.6 Moreover, once these patients are identified, other predictive biomarkers will define those in whom response will actually be associated with tissue damage prevention and among them, those in whom side effects would be tolerable. The substantial variability of disease behavior and drug metabolism and response, Inhibitors,research,lifescience,medical combined with our relative ignorance of drug mechanisms of action and long-term effects, make the implementation of this approach a complex task. However, the ubiquitin-Proteasome system understanding that improving patient quality

of life depends on such treatment has actually changed the way it is perceived with a shift from an emphasis on symptom control to attempts to modify disease course and outcomes.7 Linifanib (ABT-869) This understanding has led Inhibitors,research,lifescience,medical to efforts for creating the appropriate tools for practicing preventive care and to the understanding that it would have to be tailored and personalized as much as possible. For example, an international task force has recently created a novel MRI-based tool to measure disease damage (as opposed to disease activity)8 and a tool to measure patient disability based on international standards.9 Availability of such measurements is imperative for assessment of various treatment approaches. PREDICTING DISEASE COURSE Categorization and definition of the various disease phenotypes is a first step for tailoring therapy because treatments can be subsequently matched accordingly. The most available and straightforward approach is the use of clinical parameters.