Impact of Upadacitinib on Lipid Profile and Safety Parameters in Patients with Biologic-Refractory Ankylosing Spondylitis: A Real-World Evidence

Background: Upadacitinib, a Janus kinase (JAK) inhibitor, is an effective treatment for Ankylosing Spondylitis (AS). Although its efficacy in reducing disease activity is established, real-world data regarding its impact on li-pid profiles and laboratory parameters, particularly in biologic-refractory patients, remain limited. This study aimed to evaluate the short-term effects of Upadacitinib on inflammation, disease activity, and metabolic/lipid parameters in TNF inhibitor-experienced AS patients. Methods: This retrospective cohort study included 61 TNFi-experienced patients (100% TNFi-IR). Demographics, inflammatory markers (CRP, ESR), disease activity (BASDAI), and hematologic, metabolic, and lipid parameters were assessed at baseline, month 1, and month 3. Statistical analyses were performed using repeated measures ANOVA or Wilcoxon signed-rank tests as appro-priate. A p-value < 0.05 was considered statistically significant. Results: The mean age was 42.6 ± 10.8 years, and 55.7% were male. Median disease duration was 8 years [IQR 4–13], and baseline BASDAI was 5.8 ± 1.4. Upadaci-tinib treatment led to significant reductions in CRP (11.4 ± 10.2 → 6.9 ± 5.8 mg/L) and ESR (14.6 ± 11.5 → 10.4 ± 8.7 mm/h) by month 3 (p < 0.01). BASDAI scores improved significantly to 3.6 ± 1.2 (p < 0.001). Regarding labora-tory safety, hemoglobin and albumin levels increased significantly (p < 0.05), whereas other metabolic parameters remained stable. Lipid analysis showed significant increases in total cholesterol, LDL, and HDL by month 3 (p ≤ 0.003); however, the LDL/HDL ratio and triglyceride levels remained unchanged (p > 0.05). Conclusion: In bio-logic-refractory AS patients, Upadacitinib produced rapid and significant reductions in inflammation and dis-ease activity within 3 months. Although quantitative increases in lipid subfractions were observed, the stable LDL/HDL ratio suggests a preserved atherogenic profile, consistent with the “lipid paradox” described in in-flammatory diseases.