This systematic review evaluates the comparative efficacy and safety of oral small-molecule therapies and biologic agents in adults with moderate-to-severe ulcerative colitis (UC). Evidence from eight landmark publications encompassing multiple pivotal phase 3 randomized controlled trials was synthesized to assess induction and maintenance outcomes across distinct therapeutic mechanisms, including intracellular cytokine signaling inhibition, immune trafficking modulation, and extracellular pathway blockade. The findings suggest that oral small-molecule therapies demonstrate clinically meaningful efficacy comparable to established biologic agents while offering practical advantages related to oral administration and mechanistic diversity. Distinct differences in induction and maintenance performance across therapeutic classes highlight the importance of goal-directed therapy selection, individualized risk stratification, and mechanism-based treatment sequencing rather than class cycling alone. Overall, this review underscores the evolving role of oral therapies as integral components of contemporary UC management while emphasizing the need to balance efficacy, safety considerations, and patient-centered treatment priorities.
Zulfiqar et al. (Sat,) studied this question.