Early Lipid and Inflammatory Changes After Upadacitinib in Biologic‑Refractory SpA

In a retrospective real-world cohort of biologic-refractory spondyloarthritis, investigators reported that starting upadacitinib was followed by a rapid, parallel pattern over the first three months: fasting lipid fractions increased early (within 1–3 months) while systemic inflammation and disease activity declined over the same interval. The authors framed this divergence as potentially consistent with an inflammation-associated “lipid paradox” or broader metabolic recalibration, rather than an isolated metabolic signal. The report focuses on how metabolic markers and inflammatory measures changed during short-term follow-up.

The study evaluated 61 patients in a single-center retrospective cohort, including 51 with ankylosing spondylitis and 10 with psoriatic arthritis, all with an inadequate response or intolerance to at least one TNF inhibitor. Patients received upadacitinib 15 mg once daily, with fasting venous blood sampling and clinical assessments collected at baseline, Month 1, and Month 3. By Month 3, BASDAI decreased from 5.8 ± 1.4 to 3.6 ± 1.2 (p < 0.001), CRP declined from 11.4 ± 10.2 mg/L to 6.9 ± 5.8 mg/L (p < 0.001), and ESR decreased significantly (p = 0.002). The authors also noted that improvement was evident at Month 1 and sustained through Month 3, aligning the clinical and inflammatory trajectory with the three-month observation window.

Over the same follow-up, the investigators reported increases in fasting lipid subfractions. Total cholesterol rose from 199.4 ± 41.2 to 215.6 ± 35.4 mg/dL (p = 0.001), and LDL-C increased from 118.7 ± 33.6 to 136.5 ± 29.8 mg/dL (p = 0.003) by Month 3; HDL-C increased in parallel with a mean change of +8.5 ± 4.1 mg/dL (p < 0.001). These shifts were described as detectable by Month 1. For atherogenic indices, triglycerides did not significantly change, the LDL/HDL ratio remained stable (2.36 ± 0.8 at baseline vs 2.32 ± 0.6 at Month 3; p = 0.845), and non-HDL cholesterol increased modestly (p = 0.008). The overall pattern was presented as broadly balanced lipid increases with largely stable ratio-based indices across three months.

Short-term laboratory safety signals included a modest creatine kinase rise from 112.4 ± 54.8 to 144.2 ± 68.5 U/L (p = 0.012), which the authors stated did not exceed three times the upper limit of normal and was not accompanied by clinical evidence of myopathy. Liver enzymes (ALT, AST) and fasting glucose were reported as stable during follow-up. In the Discussion, the authors linked concurrent LDL-C and HDL-C increases with reductions in CRP/ESR and increases in albumin as consistent with reversal of the inflammatory lipid paradox and a metabolic “recalibration” accompanying inflammation control. They also described lipid monitoring and individualized cardiovascular risk assessment as relevant context for interpreting lipid changes, while noting that longer-term cardiovascular implications were not determined by their three-month data.

Key Takeaways:

• In this single-center retrospective cohort (n=61) with TNFi-inadequate response, disease activity and systemic inflammation decreased over three months after upadacitinib initiation.
• Fasting lipids increased in several subfractions over follow-up, while triglycerides and the LDL/HDL ratio were reported as stable and non-HDL cholesterol increased modestly.
• Short-term labs showed a modest CK increase without reported clinical myopathy, and the authors interpreted the lipid/inflammation pattern as consistent with a lipid-paradox/metabolic-recalibration framing alongside early lipid monitoring language.