Upadacitinib in Biologic-Experienced Inflammatory Bowel Disease: Real-World Efficacy, Safety, and Laboratory Outcomes

<i>Background and Objectives</i>: Upadacitinib is a recently approved Janus kinase (JAK) inhibitor for the treatment of inflammatory bowel disease (IBD). Although it has been adopted for clinical use, there are limited real-world data regarding its efficacy and safety, as well as its effects on laboratory parameters. In our study, we aimed to evaluate these outcomes in patients with moderate-to-severe Crohn's disease (CD) and ulcerative colitis (UC) who had previously failed biologic agents. <i>Materials and Methods</i>: This retrospective cohort study included 22 UC and 19 CD patients who received Upadacitinib for at least six months, where efficacy was assessed at pretreatment and at 3 and 6 months. We used the Harvey-Bradshaw Index (HBI) for CD and the partial Mayo score (PMS) for UC to define clinical response and remission. <i>Results</i>: All patients were biologic-experienced, with a substantial portion (47%) having previously failed at least two different agents. At six months, the persistence rates were 78.3% for CD and 88% for UC. The clinical response rates were 72.7% for CD and 83.3% for UC, while the clinical remission rates were 50% and 58.3%, respectively. Fecal calprotectin and C-reactive protein levels significantly improved (<i>p</i> < 0.001). Total, LDL, and HDL cholesterol levels increased, but triglyceride levels and the LDL/HDL ratio remained unchanged. Biochemical parameters, including glucose, HbA1c, and thyroid, kidney, and liver function tests, remained within normal limits. No clinically significant changes were observed in hemogram parameters, and no serious adverse events, embolisms, major cardiovascular events (MACEs), or deaths occurred. <i>Conclusions</i>: Upadacitinib is effective in biologic-unresponsive IBD patients. While it increases cholesterol levels, it does not alter the LDL/HDL ratio and does not demonstrate a negative effect on glucose metabolism. Further multicenter, longer-term studies are needed on this topic.