Exploring the rationale for upfront corticosteroid-JAK inhibitor combination therapy in acute severe ulcerative colitis.

UNLABELLED: Acute severe ulcerative colitis (ASUC) is a rapidly evolving, cytokine-driven immune emergency characterized by dynamic transitions from innate to adaptive inflammation. Although intravenous corticosteroids remain first-line therapy, 30-40% of patients fail to respond, and many require rescue therapy or subsequent colectomy. Sequential escalation strategies may be temporally misaligned with the accelerated immunobiology of ASUC, as delayed intervention permits immune entrenchment, cytokine redundancy, and diminished treatment responsiveness. Upfront combination therapy, initiated at hospitalization rather than after steroid failure, offers a strategy for early immune interception. Emerging randomized and cohort data suggest that early corticosteroid-JAK inhibitor combinations achieve faster clinical response and lower short-term colectomy rates compared with conventional step-up approaches. This viewpoint examines the immunopathogenic basis underpinning this strategy and synthesizes the mechanistic and clinical rationale supporting early multi-pathway intervention. By integrating evolving biological insights with emerging clinical evidence, it provides a conceptual framework to inform the use of upfront combination therapy in ASUC. FUNDING: None.