Journal Article

POS0291 BIOMARKER OF DISTURBED GUT BARRIER UNDER THERAPY WITH TNF INHIBITORS IN PATIENTS WITH AXIAL SPONDYLOARTHRITIS

Haibel, H., Spiller, L., Protopopov, M., Torgutalp, M., Proft, F., Hempel, C. M., Rios Rodriguez, V., Rademacher, J., Poddubnyy, D.

2024

Overview

Background:Patients with axial spondyloarthritis (axSpA) often exhibit microscopic intestinal inflammation and are reported to have elevated serum levels of biomarkers indicating a disturbed gut barrier, such as lipopolysaccharide-binding protein (LBP) and zonulin, compared to healthy controls [1].Objectives:To investigate the levels of zonulin, lipopolysaccharide-binding protein (LBP), and calprotectin as markers of disturbed gut barrier, bacterial translocation, and intestinal inflammation in patients with axSpA undergoing TNF inhibitor therapy and to analyze the association between disease activity, clinical response to therapy, and respective biomarker levels.Methods:Patients with radiographic axSpA (r-axSpA) from the German Spondyloarthritis Inception Cohort (GESPIC-AS) were included in this study. GESPIC-AS consists of patients with active disease at baseline, who were either biologic DMARD (bDMARD) naïve or had not been treated with bDMARDs for three months prior to enrollment. All patients began TNF inhibitor (TNFi) therapy post-enrollment. Control patients, selected from the OptiRef Study [2], presented with chronic back pain (CBP) and were confirmed not to have SpA. Serum levels of calprotectin, LBP, and zonulin were measured at baseline and after one year of TNFi treatment in patients with axSpA using commercially available ELISAs. Multivariable logistic and linear regression analyses were conducted to analyze the association between baseline biomarker levels and disease activity at baseline and after 1 year, as well as treatment response after 1 year. Treatment response was defined as a change in ASDAS ≥ 2.0 (major improvement - MI) or ≥ 1.1 (clinically important improvement - CII).Results:125 patients with r-axSpA were compared with 63 CBP controls. At baseline, r-axSpA patients had higher levels of LBP and calprotectin than controls. After one year of TNF inhibitor therapy, serum levels of calprotectin and LBP decreased significantly, with calprotectin normalizing to levels comparable to controls at baseline (Figure 1). Multivariable regression analyses showed an association between baseline LBP and calprotectin serum levels with CRP, ASDAS, and BASFI at baseline; and a negative association between baseline calprotectin levels and BASDAI and ASDAS at year 1 (Table 1). Patients responding clinically to therapy after one year exhibited higher baseline LBP serum levels. Those achieving ASDAS CII also had higher calprotectin levels at baseline. Patients achieving low disease activity (ASDAS LDA) after one year of TNF inhibitor therapy had higher baseline calprotectin levels. Baseline zonulin levels were not significantly associated with disease activity at baseline or year 1, or with treatment response.Conclusion:Patients with active r-axSpA showed higher serum levels of calprotectin and LBP compared to controls with chronic back pain. Serum levels of calprotectin and LBP decreased after one year of TNF inhibitor therapy, demonstrating an association with both clinical response and disease activity.REFERENCES:[1] Ciccia F, et al. Dysbiosis and zonulin upregulation alter gut epithelial and vascular barriers in patients with ankylosing spondylitis. Ann Rheum Dis. 2017.[2] Proft F, et al. Comparison of an online self-referral tool with a physician-based referral strategy for early recognition of patients with a high probability of axial spa. Semin Arthritis Rheum. 2020.Figure 1.Serum levels of biomarkers under TNF inhibitor therapy. Serum levels of calprotectin, LBP and zonulin at baseline (BSL) and year 1 (Y1) of patients with radiographic axial spondyloarthritis (axSpA) and of controls with chronic back pain (HD) at baseline. Pairwise comparisons by Man Whitney U Test and Wilcoxon signed rank test. *** p<0.001.Table 1. Association of biomarker serum levels at baseline and disease activity at baseline and year 1 as well as treatment response after one year of TNF inhibitor treatment.Acknowledgements:This study was supported by the MASCARA consortium (FKZ 01EC1903E, Bundesministerium für Forschung und Bildung BMBF).Disclosure of Interests:None declared.

• Publisher: BMJ Publishing Group Ltd and European League Against Rheumatism,Elsevier B.V,Elsevier Limited
• Subject: Ankylosing spondylitis / Arthritis / Back pain / biological DMARD / Biomarkers / Chronic pain / Digestive system / Dysbacteriosis / Gastrointestinal tract / Inflammation / Inflammatory diseases / Intestine / Lipopolysaccharide-binding protein / Lipopolysaccharides / Patients / Protein transport / Regression analysis / Rheumatic diseases / Scientific Abstracts / Serum levels / TNF inhibitors