P0970Efficacy and safety of upadacitinib in ulcerative colitis after prior tofacitinib exposure: real-world data from Colombia

Abstract Background Patients with ulcerative colitis (UC) who do not respond to or lose response to tofacitinib constitute a highly refractory subgroup with limited treatment options. Upadacitinib (UPA), a JAK1 inhibitor, has demonstrated superior efficacy to tofacitinib in phase 3 trials; however, routine clinical practice data for UC following tofacitinib treatment are scarce, particularly in Latin America. Methods We conducted a retrospective, multicenter study that included adults with moderate to severe UC treated with UPA 45 mg/day for induction and 30 mg/day for maintenance. Clinical response (≥3 point reduction on the Mayo scale), clinical remission (Mayo score 2), biochemical remission (CRP 5 mg/L or fecal calprotectin 150 µg/g), and corticosteroid-free remission were assessed at 8–16 weeks and 6 months. Outcomes were compared between patients with and without prior tofacitinib exposure using Fisher’s exact test and 95% confidence intervals (CI). Results Of 47 patients with ulcerative colitis, 16 (34.0%) had previously received tofacitinib; 83% had also received at least one anti-TNF agent. The mean age was 39.8 ± 14.6 years, and 59.6% had extensive colitis. At week 16, a clinical response was achieved in 81.2% (95% CI: 66.1–91.4) of patients, with no significant difference between patients who had received tofacitinib and those who had not (75.0% vs. 84.4%; p = 0.41). Clinical remission was observed in 61.7% (95% CI: 46.4–75.1), and steroid-free remission in 46.8% (95% CI: 32.1–61.9). Fecal calprotectin 150 µg/g was achieved in 36.2%, and CRP 5 mg/L in 74.5%. At 6 months, remission persisted in 55.3% of patients, including 50.0% of those who had previously received tofacitinib. No colectomies were performed in patients treated with tofacitinib, and only 1 (6.3%) discontinued treatment with UPA due to loss of response. Adverse events were mild (acne: 23.4%), with no serious infections or thromboembolic events. Conclusion In this multicentre real-world cohort from Colombia, upadacitinib showed high clinical and biochemical effectiveness in moderate-to-severe ulcerative colitis, including patients previously exposed to tofacitinib. Prior tofacitinib use did not significantly affect outcomes, indicating preserved efficacy despite prior JAK inhibition. Upadacitinib was well tolerated, with only mild adverse events. These results provide the first real-world evidence from Latin America supporting upadacitinib as an effective and safe option for difficult-to-treat ulcerative colitis. References: 1. Friedberg S, Choi D, Hunold T, Choi NK, Garcia NM, Picker EA, Cohen NA, Cohen RD, Dalal SR, Pekow J, Sakuraba A, Krugliak Cleveland N, Rubin DT. Upadacitinib Is Effective and Safe in Both Ulcerative Colitis and Crohn’s Disease: Prospective Real-World Experience. Clin Gastroenterol Hepatol. 2023 Jul;21(7):1913-1923.e2. doi: 10.1016/j.cgh.2023.03.001. Epub 2023 Mar 8. PMID: 36898598; PMCID: PMC11016252. 2. Dalal RS, Kallumkal G, Cabral HJ, Barnes EL, Allegretti JR. One-Year Comparative Effectiveness of Upadacitinib vs Tofacitinib for Ulcerative Colitis: A Multicenter Cohort Study. Am J Gastroenterol. 2024 Apr 1. doi: 10.14309/ajg.0000000000002746. Epub ahead of print. PMID: 38470031. Conflict of interest: Parra Izquierdo, Leidy Viviana: No conflict of interest Juliao Baños, Fabián: No conflict of interest Galiano, Maria Teresa: No conflict of interest Riveros, Javier: No conflict of interest Gomez Venegas, Alvaro: No conflict of interest Medrano-Almanza, Carlos Andres: No conflict of interest Ballesteros, Manuel: No conflict of interest Barreto Perez, Jonathan: No conflict of interest Cuadros, Carlos: No conflict of interest Gil Parada, Fabio Leonel: No conflict of interest Guzman, Gerardo: No conflict of interest Pico, Pedro: No conflict of interest Puentes-Manosalva, Fabian Eduardo: No conflict of interest Perea, Daniel: No conflict of interest Florez, Cristian: No conflict of interest Dr. Frías-Ordoñez, Juan: No conflict of interest