P1161 Effects of janus-kinase inhibitor therapy on lipid parameters in patients with IBD
Authors: Prabhu A , Al Dehailan R , Azzu H , Sanford J , Cripps S , Scaria L , Walsh A 
Published: January 2025

Abstract

Background
Janus-kinase (JAK) inhibitors are an oral, small molecule therapy used in the management of a range of inflammatory conditions and are associated with lipid profile changes (1-4). We evaluated whether our centre was following recommended lipid monitoring as well as the proportion and magnitude of lipid abnormalities detected.

Methods
We retrospectively collected data from all 244 patients with Inflammatory Bowel Disease (IBD) who were commenced on a JAK inhibitor, from November 2018 to January 2024, in our centre. Data was collected from our centre’s pharmacy database and the hospital’s electronic patient record. We assessed whether a baseline lipid profile was measured prior to initiating therapy and whether this was re-checked within 12 weeks of initiating therapy, as per industry recommendations. Changes in lipid parameters following therapy initiation – total cholesterol (TC) and non-HDL cholesterol (non-HDL-C) – were calculated. Where applicable, changes following the transition from a higher loading drug dose to a lower maintenance dose were quantified. Rates of initiation of lipid-lowering pharmacotherapy were also calculated.

Results
117, 76 and 51 patients were initiated on tofacitinib, filgotinib and upadacitinib respectively, with 55%, 100% and 100% of patients having had their baseline lipid profile checked prior to commencing therapy. 30%, 86% and 82% of patients had their lipid parameters re-checked within 3 months of starting therapy.
The average change in TC (mmol/L) was -0.22, 0.24, and 0.50 for tofacitinib (n=23), filgotinib (n=65) and Upadacitinib (n=42) respectively, and the average change in non-HDL-C (mmol/L) was -0.13, 0.06 and 0.32, respectively (Fig 1).
Of the patients with an abnormal lipid profile whilst receiving either tofacitinib or upadacitinib, both of which necessitate a higher induction dosing, the average subsequent decrease in TC (mmol/L) was 0.33 and 0.24 for patients receiving tofacitinib (n=12) and upadacitinib (n=11), respectively, and the average decrease in non-HDL-C was 0.40 and 0.29, respectively (median at 5 months, range 1-18 months following first abnormal lipid profile check on therapy). For filgotinib (n=27), which has stable dosing, the average decrease in TC and non-HDL-C was 0.01 and 0.05, respectively.
Statin therapy was commenced in 4/117 (3%), 2/76 (3%) and 4/51 (4%) of patients commenced on tofacitinib, filgotininb and upadacitanib, respectively, with the average reduction in TC (mmol/L) being 3.14, 1.60 and 2.00, respectively.

Conclusion
Increases in lipid parameters following the initiation of JAK inhibitor therapy in IBD patients appear to be modest, partially reversible on switching to maintenance dosing and responsive to statin therapy.

References
1.Li N, Gou ZP, Du SQ et al. Effect of JAK inhibitors on high- and low-density lipoprotein in patients with rheumatoid arthritis: a systematic review and network meta-analysis. Clin Rheumatol. 2022;41(3):677-88.
2.Wollenhaupt J, Silverfield J, Lee EB, Curtis JR, Wood SP, Soma K, et al. Safety and efficacy of tofacitinib, an oral janus kinase inhibitor, for the treatment of rheumatoid arthritis in open-label, longterm extension studies. J Rheumatol. 2014;41(5):837-52.
3.Smolen JS, Pangan AL, Emery P, Rigby W, Tanaka Y, Vargas JI, et al. Upadacitinib as monotherapy in patients with active rheumatoid arthritis and inadequate response to methotrexate (SELECT-MONOTHERAPY): a randomised, placebo-controlled, double-blind phase 3 study. Lancet. 2019;393(10188):2303-11.
4.Genovese MC, Kalunian K, Gottenberg JE, Mozaffarian N, Bartok B, Matzkies F, et al. Effect of Filgotinib vs Placebo on Clinical Response in Patients With Moderate to Severe Rheumatoid Arthritis Refractory to Disease-Modifying Antirheumatic Drug Therapy: The FINCH 2 Randomized Clinical Trial. JAMA. 2019;322(4):315-25.