Ulcerative colitis in adult patients: assessment of disease activity and severity and detection of neoplastic complications

Ulcerative colitis (UC) is a chronic, relapsing inflammatory bowel disease characterized by continuous mucosal inflammation of the colon, which not only impairs patients’ quality of life but also leads to long-term complications, including an increased risk of colorectal neoplasia. Over recent decades, therapeutic goals in UC have evolved from mere symptom control to the pursuit of objective, multidimensional treatment endpoints. From the attempt to achieve increasingly deeper remission, the concept of disease clearance (DC) has recently emerged as a more stringent and comprehensive therapeutic target. This composite outcome, defined by the simultaneous achievement of clinical, endoscopic, and histological remission, has been increasingly recognized as a marker of favorable long-term prognosis. Within this framework, the present PhD project aimed to investigate the determinants and therapeutic strategies associated with the attainment of DC in adult UC patients, as well as to evaluate the occurrence and characteristics of neoplastic complications within this population. A retrospective observational study was conducted on adult UC patients followed at the Digestive Disease Unit of the Sant’Andrea University Hospital in Rome between 2012 and 2024. Clinical, endoscopic, and histological disease activity were evaluated using validated indices, and potential predictors of DC were identified through multivariate statistical analysis. In parallel, a multicentre prospective investigation—the SVEDO Study—was carried out to assess the efficacy and safety of switching from intravenous to subcutaneous vedolizumab in UC patients in stable clinical remission. Furthermore, the long-term incidence, characteristics, and associated factors of colorectal dysplasia and carcinoma were analyzed in a separate cohort of UC patients with extensive follow-up. Among the 279 patients included in the DC analysis, 37% achieved DC after a median of 10 years from diagnosis. The absence of corticosteroid use emerged as an independent positive predictor, confirming that steroid-sparing therapeutic strategies are crucial for achieving sustained remission. Patients who reached DC experienced significantly fewer relapses, further emphasizing the clinical relevance of this comprehensive therapeutic endpoint. Interestingly, dysplastic lesions were more frequently identified among patients who achieved DC, a finding likely attributable to longer follow-up duration and more rigorous endoscopic surveillance. In the SVEDO Study, which included 168 UC patients in stable clinical remission, switching vedolizumab from the intravenous to the subcutaneous formulation proved both safe and effective. Nearly 80% of patients maintained remission at six months, with no significant biochemical or clinical deterioration observed. This treatment transition offered tangible benefits in terms of patient convenience and optimization of healthcare resources. In a separate cohort of 338 UC patients, the cumulative incidence of colorectal dysplasia and carcinoma was 11.2% and 2.7%, respectively, corresponding to annual incidence rates of 9.4 and 2.2 per 1,000 person-years. Most dysplastic lesions were small, polypoid, and endoscopically resectable, reflecting improved detection capabilities with modern high-definition endoscopy. Notably, more than half of the affected patients were in deep remission at the time of diagnosis, suggesting that neoplastic transformation may still occur in quiescent mucosa, possibly as a consequence of cumulative past inflammation. Age above 40 years was identified as the only independent risk factor associated with the development of neoplastic complications. Overall, this PhD project demonstrates that deep remission, as defined by the concept of DC, is both an achievable and clinically meaningful therapeutic goal in UC. Its attainment is associated with sustained disease control and a reduced risk of relapse, confirming its prognostic relevance in long-term management. Nevertheless, the persistence of colorectal neoplasia risk—even among patients in durable remission—underscores the importance of ongoing, individualized endoscopic surveillance. The integration of remission-oriented therapeutic strategies with lifelong, risk-adapted cancer prevention programs therefore remains fundamental to improving long-term outcomes and enhancing the quality of life of adults living with UC.