Paradoxical Massive Colonic Bleeding during Early Response to Upadacitinib in Acute Severe Ulcerative Colitis: A 3-Case Series

Introduction: Acute severe ulcerative colitis (ASUC) is associated with a substantial risk of colectomy. Upadacitinib (UPA) has demonstrated efficacy in ulcerative colitis (UC), and recent studies have suggested its potential use in ASUC. We describe 3 patients with ASUC who developed massive colonic bleeding with hypotension despite early clinical, biochemical, and endoscopic response to UPA. Case Presentation: All 3 patients had a history of treatment with corticosteroids and infliximab and presented with frequent bloody stools and elevated inflammatory markers at admission. After initiation of UPA 45 mg daily, stool frequency, hematochezia, and C-reactive protein levels rapidly improved. However, after initial resolution of hematochezia, they developed massive colonic bleeding with hypotension, requiring red blood cell transfusion. Colonoscopy at the time of bleeding showed improvement in ulceration and epithelialization of the ulcer base, whereas active bleeding was observed from fragile regenerating mucosa or exposed vessels, requiring endoscopic hemostatic treatment. In 2 patients, bleeding recurred from different sites. Following UPA discontinuation and endoscopic management, no recurrent bleeding was observed any more. Conclusion: Although gastrointestinal perforation was reported during UPA treatment, colonic bleeding has not been established as a major safety signal in patients with UC. Nevertheless, these cases suggest that massive colonic bleeding during apparent early response to UPA in ASUC may represent a possible treatment-associated event that cannot be fully explained by worsening UC activity alone.