Effectiveness of upadacitinib in ulcerative colitis patients with prior tofacitinib exposure: a systematic review and meta-analysis.

Background: Upadacitinib, a selective Janus kinase (JAK) inhibitor, is a recently approved therapy for moderate-to-severe ulcerative colitis (UC). Limited data are available on its efficacy in patients previously exposed to tofacitinib, a non-selective 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: PubMed, Embase, Web of Science, and Cochrane Library were queried for studies evaluating the effectiveness of upadacitinib in UC patients with prior tofacitinib treatment. Primary outcomes included clinical remission, steroid-free clinical remission (SFCR), and clinical response. Secondary outcomes were the mean decrease in fecal calprotectin, and adverse events. Statistical analyses were performed using R, calculating pooled proportions with 95% confidence intervals (CI) for dichotomous outcomes and mean differences with 95%CI for continuous outcomes using a random-effects model. Results: Five studies, with 127 patients, were included in the final analysis. Upadacitinib increased pooled clinical remission rates by 57% (95%CI 0.32-0.80), SFCR rates by 52% (95%CI 0.26-0.78), and clinical response rates by 75% (95%CI 0.44-0.96). Upadacitinib reduced mean fecal calprotectin levels by 597.59% (95%CI 350.94-844.324). Adverse events, such as headache, acne vulgaris, rash, nasopharyngitis and infections, were reported in 34% of patients (95%CI 0.11-0.62). Conclusions: Our meta-analysis indicates that upadacitinib may be an effective treatment for patients with prior tofacitinib exposure, demonstrating significant clinical remission, SFCR, and clinical response. Larger clinical trials are needed to establish long-term outcomes.