P0996 JAK Inhibitors Open a New Chapter in IBD Treatment: a Monocentric Retrospective Observational Research
Authors: Fu X , Zhu L 
Published: January 2025

Abstract

Background
The number of new patients with inflammatory bowel disease (IBD) in China continues to increase, the disease burden of patients is increasing, and the efficacy and safety of existing therapies are insufficient. Biologics have gradually become the main treatment for IBD, but more than 40% of patients have non-response or secondary non-response. Current studies have found that JAK-STAT is an important signaling pathway in the pathogenesis of IBD, and small molecule drug JAK inhibitors can block out downstream inflammatory pathways to achieve the purpose of alleviating the disease.

Methods
To explore the efficacy of the JAK inhibitor Upadacitinib in IBD, active IBD patients who started using Upadacitinib from February 2023 to August 2024 were retrospectively included. The baseline data and data at the end of the 12-week induction period were recorded, including demographic characteristics, symptoms, laboratory results, endoscopy and imaging results, etc. The clinical remission rate and endoscopic remission rate of Upadacitinib in the treatment of IBD were analyzed by statistical methods.

Results
By August 2024, a total of 75 patients with Crohn’s disease (CD) and 23 patients with ulcerative colitis (UC) had completed 12-week Upadacitinib induction therapy. The duration of the disease ranged from 1 to 12 years, and all of them had a history of non-response or adverse reactions to biologics before Upadacitinib treatment. The disease types of CD patients were mainly A2(16-40 years old)-L3(ileocolon)-B1(non-stricture), and 53% of them were complicated with anal fistula or perianal abscess. 62% of patients showed moderate to severe CD activity under endoscopy. After 12 weeks of use of UPA, the inflammatory indicators such as C-reactive protein, erythrocyte sedimentation rate, and fecal calprotectin were significantly decreased, and the SES-CD score as well as the CDAI score was decreased compared with the baseline level. The endoscopic response rate was 73.33%, the endoscopic remission rate was close to 50%, and the mucosal healing rate was 53%. The majority of UC patients were middle-aged and elderly men, and the Mayo scores were mainly in the moderate and severe active stage. The endoscopic subscore of 3 (severe lesions) accounted for 70.83%. At the end of the 12-week induction period, the endoscopic improvement rate reached 80%, the mucosal healing rate was 40%, and the inflammation index basically decreased to normal.

Conclusion
As a new generation of small-molecule targeted drugs, Upadacitinib has the advantages of convenient use, rapid onset, strong anti-inflammatory effect and high safety, and can significantly alleviate the disease burden of patients whose former biologics treatment has failed.

References
1.Danese S, Vermeire S, Zhou W, et al. Upadacitinib as induction and maintenance therapy for moderately to severely active ulcerative colitis: results from three phase 3, multicentre, double-blind, randomised trials. Lancet. 2022;399(10341):2113-2128. doi:10.1016/S0140-6736(22)00581-5
2.Loftus EVJ, Panés J, Lacerda AP, et al. Upadacitinib Induction and Maintenance Therapy for Crohn’s Disease. New England Journal of Medicine. 2023;388(21). doi:10.1056/NEJMoa2212728