agreement between most of the indexes (52), and they generally correlate well with endoscopic disease activity. In a prospective comparison, the PUCAI, SCCAI, and partial Mayo score demonstrated the best validity and responsiveness (51,53,54). The PRO2 (derived from components of the Mayo score) has been shown to discriminate between active drug and placebo and yielded similar effect sizes for remission when applied to previously collected clinical trial data. This has been proposed as an interim outcome measure when combined with endoscopic data (50). Ongoing efforts also aim to develop and validate PROs that incorporate patients' perception of severity of disease; (55) preliminary work suggests that such PROs correlate well with established disease activity indexes and may improve the ability to predict patient-defined remission. Previous definitions of disease severity have been used in clinical trials but not in clinical practice. Inclusion criteria for clinical trials of agents for moderately to severely active UC have required components such as (i) inability to taper off prednisone, (ii) previous failure of immunosuppressants, and (iii) moderately to severely active disease defined by the Mayo score (including the specific endoscopy subscore). In clinical trials, the definition of remission has been a Mayo endoscopic subscore of 0 or 1 and lack of rectal bleeding. In clinical practice, the previously used definitions of remission refer to clinical parameters of current relapse (number of bowel movements, bleeding, and evidence of toxicity such as vital signs or colonic dilation) but do not include objective parameters of increased disease activity other than CRP (which lacks sensitivity). These measures also do not place the current flare in the context of the previous disease course as this guideline now recommends. In addition, when using a newer disease activity definition that takes into account disease course, any patient with more than mildly active disease should be treated according to recommendations for moderately to severely active UC. In the absence of endoscopy, other objective markers of inflammation can be considered such as normalization of CRP and FC. More recent measures of remission now include symptomatic remission (no rectal bleeding and no urgency) and endoscopic evidence of mucosal healing. Retrospective data have investigated histologic remission as a potential therapeutic target and have shown histologic quiescence and histologic normalization to be predictive of relapse-free survival (56). However, only a small percentage of patients seem to reach these end points. The available data do not yet support histologic healing or normalization as a goal of treatment for patients with UC. With increasing recognition of endoscopic mucosal response and remission as treatment targets and their prognostic significance for future relapses, need for hospitalization, and surgery, it is essential to include endoscopic severity assessment in the diagnosis and management of UC (57,58). There are several tools to quantify endoscopic activity in UC, although few have been rigorously validated (59). The Mayo endoscopic score is frequently used in clinical trials and is simple to use in clinical practice, ranging from 0 for normal or inactive disease to 3 for severely active disease (46). Using a rigorous methodology for derivation and validation using regression models and central readings of recorded procedures, the UC Endoscopic Index of Severity