Selective Drug-Free Active Surveillance in Ulcerative Colitis: Biomarker-Guided, Patient-Centered Approach

Ulcerative colitis (UC) is traditionally managed with long-term 5-aminosalicylic acid (5-ASA) administration. However, in real-world practice, carefully selected low-risk patients in sustained deep remission may remain stable without continuous therapy. Randomized trials have shown only modest differences in relapse between 5-ASA and placebo treatment, and real-world experience indicates that requests to discontinue 5-ASA during sustained remission are not uncommon. Importantly, symptom-based assessments can be misleading. Psychosocial factors and a disconnect between symptoms and inflammation, including irritable bowel syndrome overlap, may explain the observed differences. Noninvasive biomarkers, such as fecal calprotectin and serum leucine-rich alpha-2 glycoprotein, allow the early detection of subclinical inflammation, supporting the feasibility of a drug-free active surveillance (DFAS) strategy in selected patients. Biomarker-guided monitoring can reduce the reliance on colonoscopy and make DFAS more acceptable in practice. Consistent with treat-to-target and disease clearance strategies, prioritizing endoscopic and histologic remission, stable biomarkers, and favorable psychosocial conditions may help identify appropriate candidates. A patient-centered implementation strategy that integrates patient-reported outcomes, mental health assessments, and shared decision-making can ensure that DFAS reflects proactive, individualized care rather than therapeutic neglect. Given the growing UC population and disease burden, increasing healthcare costs, and patient preferences to minimize long-term medication, this review defines the clinical rationale, candidate selection criteria, and a pragmatic biomarker-guided algorithm for selective DFAS after 5-ASA in UC and outlines a research agenda to validate safety, feasibility, and cost-effectiveness. We propose that DFAS be reserved for low-risk patients under structured surveillance with predefined relapse triggers and rapid rescue pathways.