P0677Time to pay attention to lipid monitoring in patients with Inflammatory Bowel Disease treated with Janus kinase inhibitors

Abstract Background Upadacitinib, a selective Janus kinase (JAK) inhibitor used to treat Inflammatory Bowel Disease (IBD), increases low-density lipoprotein cholesterol (LDL-C).1 Whilst an increased risk of major adverse cardiovascular events has not been shown in an IBD population with 3 years follow-up, the long-term effects are not known.2 The British Society of Gastroenterology guidelines recommend lipid monitoring for patients receiving JAK inhibitors,3 however, this is often overlooked as there is limited understanding on what lipid levels justify intervention. Methods We designed a local protocol based on the European Society of Cardiology 2019 lipid guidelines4 using the LDL-C intervention thresholds specified in the low cardiovascular risk category. Patients with an LDL-C ≥3.0 mmol/L were recommended lifestyle changes; and drug therapy suggested if the LDL-C remained elevated. Patients with LDL-C ≥4.9 mmol/L were recommended lifestyle and drug intervention concomitantly. Upadacitinib’s effect on LDL-C is dose-dependent, so raised LDL-C during loading-dose was only actioned if it persisted on the lower maintenance-dose. Data were collected between October 2023 and September 2025 at a busy general hospital at three timepoints: prior to initiation, during loading-dose induction, and after at least four weeks on the reduced maintenance-dose. Results 29 patients had LDL-C levels measured once established on maintenance-dose upadacitinib. The median age was 35 years (IQR 29-47); 18 (62%) were male, 21 (72%) had Ulcerative Colitis, and 8 had Crohn’s disease. The mean LDL-C changed from pre-treatment values of 2.64 mmol/L (SD = 0.88) to 3.17 mmol/L (SD = 1.18) during high-dose therapy, and to 3.06 mmol/L (SD = 1.12) on maintenance-dose therapy. There was a statistically significant increase between pre-treatment and maintenance-dose levels (p = 0.02). Before starting upadacitinib, 10/29 (34%) patients had mildly elevated LDL-C ≥3.0 mmol/L; none had LDL-C ≥4.9 mmol/L. During high-dose upadacitinib, 15/29 (52%) had LDL-C ≥3.0mmol/L, of whom 4 (14%) had LDL-C ≥4.9 mmol/L. On-maintenance-dose upadacitinib, 15/29 (52%) had LDL-C ≥3.0 mmol/L, of whom 3 (10%) had LDL-C ≥4.9mmol/L; 52% would require lifestyle intervention and possible drug intervention with 31% receiving this, and 10% would be eligible for lifestyle and concomitant drug intervention, with all three patients being appropriately referred for treatment. Conclusion By taking an active approach to lipid management at our centre, 52% of patients on maintenance upadacitinib had persistently raised LDL-C meriting lifestyle advice and at least 10% will require statins. This study highlights the lack of evidence in this cohort and underscores the need for long-term data as upadacitinib use continues to expand. References: 1. Makris A, Barkas F, Sfikakis PP, Liberopoulos E, Agouridis AP. The effect of upadacitinib on lipid profile and cardiovascular Events: A Meta-Analysis of Randomized Controlled Trials. Journal of Clinical Medicine. 2022;11(23):6894. doi:10.3390/jcm11236894 2. Panaccione R, Vermeire S, Danese S, et al. Long-term efficacy and safety of upadacitinib in patients with moderately to severely active ulcerative colitis: an interim analysis of the phase 3 U-ACTIVATE long-term extension study. The Lancet Gastroenterology and Hepatology. 2025;10(6):507-19. 3. Moran GW, Gordon M, Sinopolou V, et al. British Society of Gastroenterology guidelines on inflammatory bowel disease in adults: 2025. Gut. 2025;74(Suppl 2):s1-s101. doi:10.1136/gutjnl-2024-334395 4. Mach F, Baigent C, Catapano AL, et al. 2019 ESC/EAS Guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk. European Heart Journal. 2019;41(1):111-188. doi:10.1093/eurheartj/ehz455 Conflict of interest: Dr. Ubhi, Nicholas: No conflict of interest Shaikh, Meshael: No conflict of interest Alhakem, Hussein: No conflict of interest Mohamed, Zameer: No conflict of interest Johnston, Emma: No conflict of interest Bouri, Sonia: No conflict of interest