Letter to the Editor: Can upadacitinib dose escalation redefine treatment strategies in refractory inflammatory bowel disease?

Despite major advances in inflammatory bowel disease (IBD) therapeutics, secondary loss of response remains a persistent clinical challenge. Upadacitinib, a selective Janus kinase-1 inhibitor, has demonstrated efficacy in both ulcerative colitis and Crohn's disease; however, real-world patients frequently experience declining response during maintenance therapy. In this editorial, we discuss the findings of Ellington et al, who evaluated upadacitinib dose re-escalation to 45 mg daily in patients with refractory IBD and secondary loss of response. In their retrospective single-center cohort study involving 56 heavily treatment-experienced patients, dose escalation was associated with significant improvement in abdominal pain, hematochezia, urgency, and diarrhea, along with reduced corticosteroid exposure and favorable treatment durability. Objective inflammatory markers and endoscopic outcomes improved numerically but did not achieve statistical significance. These findings highlight the growing importance of individualized therapeutic optimization in IBD management while also underscoring the need for careful patient selection, long-term safety monitoring, and prospective comparative studies. Although current evidence remains preliminary, upadacitinib dose escalation may represent a pragmatic rescue strategy for selected patients with refractory disease.