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 as well as other extraintestinal comorbidities.