S4959 Intestinal Perforation in an Ulcerative Colitis Patient Following Upadicitinib Initiation

Introduction: The non-selective Janus-Kinase (JAK) inhibitor, tofacitinib, has been associated with bowel perforation in ulcerative colitis (UC) patients. Upadacitinib (UPA), a selective Janus-Kinase inhibitor, has rarely been associated with bowel perforation in Crohn’s disease (CD), and less commonly so in patients with UC. We present a rare case of bowel perforation in a UC patient 3 months after initiating UPA. Case Description/Methods: A 31-year woman had a history of iron deficient anemia and UC for 9 years. After having failed or lost response to infliximab, azathioprine, vedolizumab, ozanimod, and ustekinumab, she started UPA with a significant improvement in fecal urgency and frequency of her bowel movements. Her C-reactive protein correspondingly improved from 18.1 to 5.3 mg/dL. She presented to an outside hospital with nausea, vomiting, and right lower quadrant tenderness. She had an elevated white blood cell count of 13.0 × 103 mcl as well as microcytic anemia with a hemoglobin of 11.0 g/dL. A computed tomography scan with intravenous contrast showed peri-colonic inflammation about the mid-transverse colon with extraluminal gas and posterior wall penetration without a drainable fluid collection. The left and right portions of the colon were decompressed with diffuse mucosal enhancement. She was not taking nonsteroidal anti-inflammatory agents or systemic corticosteroids for 4 months and had no history of perforations. The patient was conservatively managed with antibiotics and bowel rest, and her symptoms resolved over the course of a week. After follow-up, the UPA was discontinued, and she was initiated on adalimumab. Discussion: Prior investigations of perforation during UPA use in IBD reflect that the occurrences are so rare, it is difficult to determine whether they represent a true safety concern. The U-ACTIVATE UPA extension trial reported a colon perforation in a 70-year-old man. In the CD trials leading to approval of UPA, the U-EXCEL, U-EXCEED, and U-ENDURE reported 4 cases of perforation in the induction phase and 2 in the maintenance phase of the trials. In these cases, the patients had CD with active disease, deep ulcers, or strictures in the perforated areas, suggesting it might have been related to the natural course of their disease. In the case of our UC patient, her disease activity had improved in the months prior to her hospitalization. While rare, providers should consider discussing the risk of perforation in UC patients prior to initiation of UPA.