Association of serum uric acid with circulating inflammatory proteins and treatment response to ixekizumab in patients with psoriasis: A multicenter prospective cohort study in China

Abstract

Abstract Background: Serum uric acid (SUA) has been implicated in various inflammatory conditions, yet its association with inflammatory proteins and treatment outcomes in psoriasis remains unclear. This study aimed to investigate the association of SUA levels with specific circulating inflammatory proteins and treatment response to ixekizumab, a monoclonal antibody against interleukin-17A, in patients with moderate-to-severe psoriasis. Methods: Patients attending 26 dermatology centers across China were recruited into this real-world prospective cohort study conducted between August 2020 and May 2022. The SUA levels of the participants were measured to assess hyperuricemia, and treatment response was evaluated using the Psoriasis Area and Severity Index (PASI). All participants received ixekizumab at a dose of 160 mg at week 0, followed by 80 mg every 2 weeks through week 12. Adjusted logistic regression analysis was used to explore differences in treatment response between patients with and without hyperuricemia. The restricted cubic spline (RCS) was employed to explore the continuous relationship between SUA and the response outcomes. Specifically, we measured 92 circulating plasma inflammatory markers using the Olink Proteomics. Results: A total of 390 patients with psoriasis were included in the study. The psoriasis patients with hyperuricemia demonstrated a higher prevalence of obesity, hyperlipidemia, and hyperglycemia compared with those without hyperuricemia. After 12 weeks of ixekizumab treatment, patients with hyperuricemia exhibited a lower likelihood of achieving PASI 75 (adjusted odds ratio [aOR] 0.84, 95% confidence interval [CI] 0.69–0.99), PASI 90 (aOR 0.37, 95% CI 0.15–0.62), and PASI 100 (aOR 0.57, 95% CI 0.37–0.91). Olink Proteomics identified significant correlations between SUA concentration and the levels of 26 circulating inflammatory proteins, and pathway analysis showed enrichment of pathways such as response to tumor necrosis factor (TNF), lymphocyte activation, and cytokine activity. Conclusion: Elevated SUA levels can hinder the effectiveness of ixekizumab and positively correlate with specific circulating inflammatory proteins in patients with psoriasis, emphasizing the need for further investigation and consideration of metabolic factors in psoriasis management strategies. Trial registeration: Chinese Clinical Trial Registry (ChiCTR2000036186)