What Does Disease Progression Look Like in Ulcerative Colitis, and How Might It Be Prevented?

Ulcerative colitis (UC) has been characterized by inflammation limited to the mucosa. Although sustained and durable remission has been associated with mucosal healing, the recurrent phenomenon of persistent clinical disease activity despite mucosal healing has been observed in clinical practice and across pivotal trials. Over time, UC appears to confer an increased risk of progression, defined as changes of disease phenotype; adverse transmural effects on the bowel wall; increased risk of neoplasia development; worsening colorectal function; and increased risk of colectomy, hospitalizations, and other extraintestinal comorbidities. Although the treatment paradigm for Crohn's disease has shifted toward early aggressive intervention to prevent disease progression and irreversible bowel damage, such urgency in efforts to halt disease progression in UC have been largely overlooked. This review summarizes the multiple facets of UC contributing to a modified perception of the disease as a progressive one. We propose further study of the natural history and priorities for further treatment goals that include these considerations. disease control. Such disease progression in UC may be defined in phenotypic, structural, functional, or comorbidity terms. This review discusses those features that suggest that UC is, in fact, a progressive disease (Figure 1) and, given this thesis, that the endpoints of treatment and goals of man-agement should include prevention of progressive damage and associated dysfunction, neoplasia, and potentially a variety of extraintestinal consequences. We highlight the gaps in our knowledge and where further investigation is needed and propose a reappraisal of disease-monitoring strategies, treatments, and clinical trial designs that address these important issues.