Sequential rescue therapy with JAK inhibitors in corticosteroid and infliximab-refractory acute severe ulcerative colitis: a case series

Acute severe ulcerative colitis (ASUC) is a life-threatening medical emergency affecting over 20% of patients with ulcerative colitis (UC). Up to 40% of patients are refractory to intravenous corticosteroids (IVCS) and require rescue medical therapy or immediate colectomy. The potent Janus kinase (JAK) inhibitors, upadacitinib and tofacitinib, have proven efficacy in a randomised control trial setting for moderate-to-severe UC, but not ASUC. We describe a case series of sequential rescue therapy with JAK inhibitors following the failure of dose-intensified infliximab in corticosteroid-refractory ASUC. Six adult (>16 years old) patients received sequential rescue therapy with a JAK inhibitor (upadacitinib <i>n</i> = 5, tofacitinib <i>n</i> = 1) following failure of IVCS and dose-intensified infliximab at the Royal Brisbane and Women's Hospital (QLD, Australia) between October 2023 and April 2024. All patients met the Truelove and Witts criteria for ASUC on admission. Data were captured during admission and at 90-days post-discharge. Co-primary outcomes were 90-day colectomy-free survival and inpatient clinical response (<4 non-bloody stools per day) 72 h after JAK-inhibitor initiation. Secondary outcomes included 90-day clinical (PRO-2 score < 1) and biochemical (faecal calprotectin (FCP) < 150 µg/g and C-reactive protein (CRP) < 5 mg/L) corticosteroid-free remission and adverse events. Median CRP on admission was 100 mg/L (interquartile range (IQR) 58-105), median FCP 3400 µg/g (IQR 910-4950) and median Mayo Endoscopic Score 3. Four out of six patients had a clinical response within 72 h of sequential JAK-inhibitor rescue therapy. Two patients underwent emergent inpatient colectomy for refractory disease - one of whom developed post-operative sepsis. Among the four JAK-responders at 90 days, all achieved corticosteroid-free clinical remission and three achieved biochemical remission. No other adverse events were recorded. There is a promising role for JAK inhibitors as sequential rescue therapy following the failure of dose-intensified infliximab in select patients with corticosteroid-refractory ASUC.