S1775 Effectiveness of Upadacitinib in Ulcerative Colitis Patients With Prior Tofacitinib Exposure: A Systematic Review and Meta-Analysis

Introduction: Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by diarrhea, abdominal pain, hematochezia, and tenesmus. Over the past 2 decades, several biologics and small-molecule therapies have been approved for the treatment of moderate-to-severe UC, including Upadacitinib, an oral selective small-molecule Janus Kinase (JAK) inhibitor, which was approved by the US Food and Drug Administration (FDA) in March 2022. However, limited data is available on its efficacy in patients previously exposed to Tofacitinib, a first-generation non-selective oral JAK inhibitor. Therefore, we conducted a systematic review and meta-analysis to evaluate the efficacy of Upadacitinib in UC patients with prior tofacitinib treatment. Methods: Following Cochrane and PRISMA guidelines, we systematically reviewed 4 databases; PubMed, Embase, Web of Science, and the Cochrane Library, for studies evaluating the effectiveness of Upadacitinib in UC patients with prior exposure to Tofacitinib. Statistical analyses were performed using R version 4.4.1, calculating pooled proportions with 95% confidence intervals (CIs) for dichotomous outcomes and mean differences (MDs) with 95% CIs for continuous outcomes using a random-effects model. Proportional data were transformed using the Freeman-Tukey double-arcsine method, and variance was calculated using the restricted maximum-likelihood estimator. Results: We included 6 studies in our final analysis. All included studies evaluated the effectiveness of upadacitinib in UC patients previously treated with tofacitinib. The meta-analysis revealed that upadacitinib increased pooled clinical remission rates by 57% (95% CI: 0.32–0.80; I2 = 84%; P < 0.01), steroid-free clinical remission rates by 52% (95% CI: 0.33–0.72; I2 = 61%; P = 0.05), and clinical response rates by 70% (95% CI: 0.57–0.82; I2 = 35%; P = 0.21). Additionally, Upadacitinib reduced mean fecal calprotectin levels by 593.19 points (95% CI: 349.06–837.31; I2 = 35%; P = 0.21). Adverse events associated with Upadacitinib, such as headache, acne vulgaris, rash, nasopharyngitis, and infections, were reported in 31% of patients (95% CI: 0.14–0.51; I2 = 71%; P = 0.02). Conclusion: Our meta-analysis indicates that upadacitinib may be an effective treatment for patients with prior tofacitinib exposure, as it achieves significant clinical remission, steroid-free clinical remission, and clinical response. Larger prospective studies are needed to confirm and validate these findings.