Lack of Benefit for Early Escalation to Advanced Therapies in Ulcerative Colitis: Critical Appraisal of Current Evidence

Although ulcerative colitis (UC) shares many common pathways and therapeutic options with Crohn's disease (CD), CD patients are four times more likely to undergo surgery 10 years into their disease in biologic era and are more likely to have extraintestinal manifestations than UC patients. Early treatment in CD has been demonstrated to modify natural history of disease and potentially delay surgery. Previous reviews on this topic borrowed their evidence from CD to make UC-specific recommendations. This review highlights the emergence of UC-specific data from larger cohort studies and a comprehensive individual patient data systemic review and meta-analysis to critically appraise the evidence on utility of early escalation to advanced therapies with respect to short-, medium-, and long-term outcomes. In UC, the utility of the early escalation concept for the purposes of changing the natural history, including reducing colectomy and hospitalisations, is not supported by the available data. Data on targeting clinical, biochemical, endoscopic, and histological outcomes are needed to demonstrate that they are meaningful with regards to achieving reductions in hospitalization and surgery, improving quality of life, and minimizing disability. The analyses of different populations of UC patients, such as those with "relapsing & remitting" disease or with severe or complicated disease course, are urgently needed. The costs and risk/benefit profile of some of the newer advanced therapies should be carefully considered. In this clinical landscape, it appears premature to advocate an indiscriminate 'one size fits all' approach to escalating to advanced therapies early during the course of UC.