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Background The optimal first-line treatment strategy for moderate-to-severe ulcerative colitis (UC) remains associated with an implementation gap. Although international guidelines recommend early use of biologics, traditional step-up therapy remains predominant in Asian clinical practice due to cost and safety concerns. This study aimed to fill the long-term evidence gap in strategy comparison by evaluating the differential long-term benefits between an early top-down strategy and a conventional step-up strategy in the context of Asian healthcare resources.Methods This prospective, multicenter, real-world cohort study enrolled patients with moderate-to-severe UC who initiated induction therapy with infliximab or glucocorticoids based on shared decision-making between physicians and patients. The primary endpoint was clinical remission at week 14; secondary endpoints included endoscopic remission, deep remission, treatment outcomes during up to three years of follow-up, treatment durability, and safety profile. IPTW was applied to adjust for baseline covariates.Results A total of 278 patients were enrolled across six tertiary centers (infliximab group: 188; glucocorticoids group: 90) ( IDDF2026-ABS-0520 Figure 1). After IPTW adjustment, all baseline covariates were effectively balanced (IDDF2026-ABS-0520 Figure 2). At week 14, infliximab demonstrated superior induction effectiveness compared to glucocorticoids: clinical remission (55.6% vs. 25.8%, P < 0.001; adjusted odds ratio = 3.589, 95% confidence interval: 2.098–6.298), endoscopic remission (48.7% vs. 33.9%, P = 0.020), and deep remission (39.0% vs. 23.3%, P = 0.010) (IDDF2026-ABS-0520 Figure 3). Long-term outcomes consistently favored early infliximab therapy, with higher clinical remission rates at week 52 (57.8% vs. 29.8%, P < 0.001), week 104 (40.0% vs. 17.9%, P < 0.001), and week 156 (19.6% vs. 6.9%, P = 0.008) (IDDF2026-ABS-0520 Figure 4). PSM analysis confirmed robust consistency in effectiveness outcomes (IDDF2026-ABS-0520 Figure 5). Infliximab showed better treatment durability (adjusted hazard ratio = 0.508, 95% confidence interval: 0.330–0.781, P = 0.002) (IDDF2026-ABS-0520 Figure 6). The incidence of adverse events was lower in the infliximab group (6.4% vs. 16.7%, P = 0.007), with no cases of tuberculosis or hepatitis B reactivation observed.Conclusions In a biologicnaïve Asian population, early introduction of an infliximab-based strategy demonstrated superior durable remission and a more favorable safety profile compared to the conventional glucocorticoidbased induction approach, supporting earlier initiation of biologics in the clinical pathway.Abstract IDDF2026-ABS-0520 Figure 1Abstract IDDF2026-ABS-0520 Figure 2Abstract IDDF2026-ABS-0520 Figure 3Abstract IDDF2026-ABS-0520 Figure 4Abstract IDDF2026-ABS-0520 Figure 5