A Real-World Study of Upadacitinib in Anti-TNF Refractory Crohn’s Disease: Effectiveness, Persistence, and Safety

Purpose: Real-world evidence on the effectiveness of upadacitinib in Crohn’s disease is increasing; however, data from Chinese populations remain limited. This study aimed to evaluate the real-world effectiveness, persistence, and safety of upadacitinib. Methods: This retrospective study included consecutive patients with Crohn’s disease treated with upadacitinib at the First Affiliated Hospital of Anhui Medical University who had at least one follow-up visit. Clinical effectiveness was assessed using the Harvey-Bradshaw Index, and endoscopic effectiveness was evaluated using the Simple Endoscopic Score for Crohn’s Disease. Logistic regression analysis was performed to identify factors associated with clinical remission at week 12. Kaplan-Meier analysis and Cox regression analysis were used to evaluate upadacitinib persistence. Results: Total of 108 patients with moderate-to-severe Crohn’s disease and prior anti-TNF failure or intolerance were included. The clinical remission rates at weeks 12 and 24 were 55.1% and 52.5%, respectively, whereas the biomarker remission rates were 57.3% and 62.5%, respectively. Endoscopic reassessment was available for 32 patients. Endoscopic response was achieved in 16 patients (50.0%), of whom 8 (25.0%) attained endoscopic remission. Pharmacokinetic data from a small subset of 24 patients showed that higher plasma concentrations of upadacitinib were associated with endoscopic remission ( p = 0.023). Stricturing Crohn’s disease (OR = 0.32, 95% CI: 0.12– 0.84, p = 0.021) and baseline albumin ≤ 35 g/L (OR = 0.22, 95% CI: 0.07– 0.62, p = 0.006) were associated with a lower likelihood of clinical remission at week 12. Twenty patients discontinued treatment, and baseline albumin ≤ 35 g/L (HR = 3.05, 95% CI: 1.26– 7.36, p = 0.012) was associated with an increased risk of discontinuation. A total of 22 (20.3%) patients experienced 23 adverse events. Conclusion: This real-world study demonstrates that upadacitinib is effective, with acceptable safety and favorable treatment persistence, in Chinese patients with moderate-to-severe anti-TNF-refractory Crohn’s disease. Future studies with larger sample sizes should focus on long-term effectiveness and safety and provide more comprehensive pharmacokinetic characterization. Keywords: upadacitinib, janus kinase inhibitor, crohn’s disease, real-world evidence