POS0341\u2005sVCAM-1 EXPRESSION IN TAKAYASU ARTERITIS TREATED WITH TOCILIZUMAB: A PROSPECTIVE PILOT STUDY

Abstract

Takayasu arteritis (TA) is a rare disease, its diagnosis is often delayed by years. Biomarkers might be helpful for earlier diagnosis and for monitoring treatment. We have described serum soluble vascular cell adhesion molecule-1 (sVCAM-1) as a marker of inflammation in a variety of rheumatic diseases, including vasculitis (1). Tocilizumab (TCZ) is a monoclonal antibody against the interleukin-6 receptor with established benefits in TA (2). It may spare oral glucocorticoids (GC) and Disease-Modifying Agents (DMARDs). So far, sVCAM-1 has never been examined as diagnostic marker or to monitor disease activity in TA patients treated with TCZ.To analyze sVCAM-1 in TA patients treated with TCZ in a prospective clinical trial and compare these results to age-matched healthy controls (HC) as well as DMARDs. In addition, MRI analyses of aortic wall thickening and enhancement might serve as a morphologic correlate of serologic disease activity.29 TA patients were prospectively followed between 2016 and 2019 (27 females, mean ± SD: 39.2±13.9 years) at the Department of Rheumatology of the University Hospital of Bern, Switzerland. At baseline, patients were without treatment (n=8) or treated with TCZ (n=13), GC (n=4), GC + methotrexate (MTX) (n=1), infliximab (IFX) + MTX (n=1), GC + IFX (n=1), MTX (n=1). Three follow-ups were performed after an average of 12, 24, 34 ± 3 months. sVCAM-1 was measured in serum using a commercially available ELISA kit (R&D Systems, Germany). Results were compared to 29 sera of matched HC (27 females, 40.8±15.1 years). MRI of aortic changes were scored on a scale of 0 (no thickening and vessel wall enhancement) to 3 (maximal thickening and vessel wall enhancement). Cumulated sVCAM-1 concentrations from each MRI scoring group (0-3) were compared to HC in order to determine if sVCAM-1 from high aortic MRI inflammation was significantly elevated.At baseline, significantly increased serum concentrations of sVCAM-1 (ng/ml) were observed in TA patients without treatment (n=8, 537.3±130.1, p=0.002) vs. HC (336.0±76.1). A smaller difference was found between patients under treatment and HC (n=21, 468.2±105.3 vs. 405.1±82.5, p=0.04). Follow-ups in the TCZ group showed 518.9±138.9 vs. 417.5±46, p=0.12 (n=6) after 12 months, 436.6±77.3 vs. 399.6±113.1, p=0.46 (n=8) after 24 months and 407.1±27.1 vs. 381.8±60.4, p=0.47 (n=4) after 36 months. In contrast, patients under DMARD therapy showed values of 505.8±126.4 vs. 395.6±60.2 p=0.04 (n=8) after 12 months, 437.8±76.2 vs. 396.4±91.9, p=0.24 (n=12) after 24 months and 440±43.3 vs. 323±50 p=0.03 (n=8) after 36 months. MRI analyses showed that group 0 (no inflammation, n=7) had significant increased values compared to HC (474.7±106.8 vs. 356.9±48.8, p=0.02), and group 3 (maximal inflammation, n=11) was also elevated (461.8±98.4 vs. 379.3±88.9, p=0.05).The results suggest that sVCAM-1 is a biomarker of disease activity in patients with TA. The results at follow-up show that sVCAM-1 decreased more rapidly under treatment with TCZ compared to treatment with DMARDs. Remarkably, sVCAM-1 concentrations did not correlate with disease activity as assessed with MRI.[1]Oleszowsky M, Seidel MF. Serum Soluble Vascular Cell Adhesion Molecule-1 Overexpression Is a Disease Marker in Patients with First-Time Diagnosed Antinuclear Antibodies: A Prospective, Observational Pilot Study. BioMed Res Int. 2018;8286067.[2]Hellmich B, Agueda A, Monti S, Buttgereit F, Boysson H de, Brouwer E, et al. 2018 Update of the EULAR recommendations for the management of large vessel vasculitis. Ann Rheum Dis. 2020 Jan 1;79(1):19–30.None declared