Real-World Experience of Upadacitinib in Treatment of Adults with Moderate to Severe Ulcerative Colitis

Introduction: Ulcerative colitis (UC) is a type of inflammatory bowel disease characterized by chronic inflammation of the colon and often requires long term medical therapy.Upadacitinib is a selective Janus kinase inhibitor approved by the Federal Drug Administration (FDA) in March 2022 for the treatment of patients with moderate to severe chronic ulcerative colitis (UC) with prior inadequate response or intolerance to anti-tumor necrosis factor alpha agents (TNF-a). The aim of this study was to describe the effectiveness and safety of UPA in moderately severe UC patients who had previously failed major biologic therapy. Methods: We conducted a retrospective study of adult patients (age >18 years) with moderate to severe UC who were prescribed UPA at Mayo Clinic locations in Rochester, Florida and Arizona. We conducted a search of the electronic medical records to identify patients with UC who had failed therapy with one or more biologic agents and were subsequently treated with Upadacitinib. Data were collected on demographics, prior medications, labs and endoscopy. The primary outcome was clinical response as described by patient symptoms of overall well being, stool frequency and abdominal pain. Secondary outcome included adverse events and outcomes of treatment failures. Results: Out of the 87 patients treated with upadacitinib, 54 were male ( 62%) and 33 were female (38%), 80 (93%) patients were white, median age was 37 years ( range 18-70). Pretreatment labs included mean hemoglobin of 12 gm/dl (7-15), CRP of 21 mg/L ( 1-61), serum albumin 3.9 g/dl ( 2.2-5), fecal calprotectin of 1348 (113-3469). All the patient's had used prior biologics and steroids. Baseline Mayo score of 2 or 3 was noted in 98% patients. Anti TNF had been used in 86 ( 98%) patients. Tofacitinib had been used in 17 patients ( 20%). 74 patients had clinical improvement over a follow up period of 106 days (10-350 days) suggesting an overall clinical response of 85% (95% Confidence interval [CI] 50%-96%). Thirteen patients did not improve out of which nine required colectomy and four were managed with different medical therapy (Table 1). Conclusion: Treatment with UPA resulted in clinical response was in 85% of patients. Of the 15 % non responders, 10% ultimately required definitive surgical management. UPA was well tolerated and serious adverse effects were only noted in one patient. Our study suggests that UPA is a safe and effective treatment option in the management of patients with UC previously refractory to other biologic agents. Table 1. - Baseline patient characteristics (UPA in UC) Mean pretreatment lab parameters Hemoglobin g/dl 12 (7-15) CRP mg/L 21 (1-61) Fecal calprotectin 1348 (113-3469) Albumin g/dl 3.9 (2-2.5) Prior Medication use Anti TNF 86 (98%) Tofacitinib 17 (20%) Pretreatment Endoscopic Mayo Score 71 Mayo 2 or 3 69 (98%)