Effects of upadacitinib on lipid profiles and their relationship with inflammation in patients with inflammatory bowel disease: a real-world longitudinal cohort study

Background Upadacitinib (UPA), a selective Janus kinase 1 inhibitor, is approved for moderate-to-severe inflammatory bowel disease (IBD). JAK inhibitors affect lipid metabolism, but longitudinal real-world data on lipid changes during UPA therapy, and their relation to inflammatory activity, are scarce. Methods In this single-center retrospective cohort study, patients with ulcerative colitis or Crohn’s disease treated with upadacitinib were followed for up to 2 years. Serial fasting lipid profiles and inflammatory markers (fecal calprotectin, C-reactive protein [CRP], high-sensitivity CRP) were collected at baseline, end of induction (weeks 8-12), 1 year, and 2 years. Lipid trajectories were analyzed with linear mixed-effects models; paired changes were compared with paired t-tests. Results Among 159 patients (mean age 43.3 ± 14.0 years; 62.3% male), total cholesterol (TC) rose from 4.19 ± 0.87 mmol/L at baseline to 4.92, 5.03, and 5.21 mmol/L at the end of induction, 1 year, and 2 years (mixed-effects estimates +0.70 to +0.90; all P < .001). Low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) rose in parallel, and the LDL-C/HDL-C ratio did not increase. CRP reductions correlated with lipid rises (Spearman rho = −0.45 to −0.47; all P ≤ .02). No cardiovascular death, myocardial infarction, or stroke occurred (0/159); one venous thromboembolism and 3 hypertension cases were recorded. Conclusions In patients with IBD treated with UPA, TC and LDL-C rose modestly alongside the resolution of inflammation; HDL-C improved and the LDL-C/HDL-C ratio did not increase. Lipid monitoring and individualized cardiovascular risk assessment are warranted during UPA therapy.