Clinical outcomes of upadacitinib dose escalation in inflammatory bowel disease: A single-center retrospective cohort study

BACKGROUND Upadacitinib is a selective Janus kinase-1 (JAK1) inhibitor approved for the treatment of moderate-to-severe ulcerative colitis (UC) and Crohn’s disease (CD). Standard therapy consists of induction dosing at 45 mg daily followed by maintenance dosing of 15-30 mg daily. Although pivotal trials demonstrated sustained efficacy with maintenance therapy, secondary loss of response occurs in clinical practice. Data regarding the effectiveness of dose re-escalation remain limited. AIM To evaluate clinical outcomes following upadacitinib dose escalation in inflammatory bowel disease (IBD) with loss of response to maintenance dosing. METHODS We conducted a single-center retrospective cohort study of adults with IBD who underwent re-escalation to upadacitinib 45 mg daily beyond the labeled induction period. Data were obtained through electronic medical record review. The primary endpoint was clinical response, defined as provider-documented symptom improvement and/or objective improvement in biomarkers or endoscopic assessment. Secondary outcomes included indications for escalation, corticosteroid exposure, IBD-related healthcare utilization, and treatment durability. RESULTS A total of 56 patients were included [38 CD, 18 UC; median age 34 years (interquartile range: 26-46), 43% female] with a mean of 2.49 prior biologic exposures. Among 49 patients with paired symptom data, abdominal pain decreased from 57% to 29% (P = 0.003), hematochezia from 49% to 20% (P = 0.004), urgency from 45% to 16% (P = 0.003), and diarrhea from 55% to 37% (P = 0.049). Corticosteroid use declined from 50% to 32% (P = 0.031). The proportion with ≥ 1 IBD-related hospitalization or emergency department visit decreased from 32% to 20%. Biomarkers and endoscopic outcomes improved numerically but were limited by small paired samples. At most recent follow-up, 89% of patients remained on escalated dosing. CONCLUSION In this single-center cohort, upadacitinib dose escalation improves symptoms and reduces corticosteroid use, supporting dose intensification as a pragmatic strategy for secondary loss of response.