25rhk049 10.3205/25rhk049 urn:nbn:de:0183-25rhk0499 Meeting Abstract Schirmer Schirmer Jan J

University Medical Center Schleswig-Holstein, Rheumatology, Internal Medicine I, Kiel

author Geisen Geisen Ulf U

University Medical Center Schleswig-Holstein, Rheumatology, Internal Medicine I, Kiel

author Ketelsen Ketelsen Hannah H

University Medical Center Schleswig-Holstein, Rheumatology, Internal Medicine I, Kiel

author Hoyer Hoyer Bimba B

DLR, Clinical Air and Space Medicine, Cologne

author Jacobs Jacobs Gunnar G

Kiel University, Institute of Epidemiology and Biobank popgen, Kiel

author Schreiber Schreiber Stefan S

University Medical Center Schleswig-Holstein, Internal Medicine I, Kiel Kiel University, Institute for Clinical Molecular Biology, Kiel

author Leipe Leipe Jan J

University Medical Center Schleswig-Holstein, Rheumatology, Internal Medicine I, Kiel

author Waschina Waschina Silvio S

Kiel University, Division of Food Technology, Human Nutrition and Food Science, Kiel

author German Medical Science GMS Publishing House

Düsseldorf

610 20250917 engl This is an Open Access article distributed under the terms of the Creative Commons Attribution 4.0 License. Dieser Artikel ist ein Open-Access-Artikel und steht unter den Lizenzbedingungen der Creative Commons Attribution 4.0 License (Namensnennung). M0627 049 Deutsche Gesellschaft für Rheumatologie Deutsche Gesellschaft für Orthopädische Rheumatologie 53. Kongress der Deutschen Gesellschaft für Rheumatologie (DGRh), 39. Jahrestagung der Deutschen Gesellschaft für Orthopädische Rheumatologie (DGORh) Deutscher Rheumatologiekongress 2025 Experimentelle & Translationale Rheumatologie Wiesbaden 20250917 20250920 ET.32 TextIntroduction: Interleukin 6 (IL-6) plays a central role in the pathogenesis of rheumatoid arthritis (RA). While classic IL-6 signalling involves membrane-bound IL-6 receptors (IL-6R), trans-signalling involves soluble IL-6 receptors (sIL6R) and membrane-bound glycoprotein 130 (gp130). Soluble gp130 (sgp130) inhibits IL-6 trans-signalling. Understanding how IL-6 signalling components respond to targeted therapies may offer mechanistic insights.Methods: Serum samples were collected from patients with active arthritis at baseline and 3–6 months after treatment intensification with a targeted therapy. IL-6, sIL6R and sgp130 concentrations were measured by ELISA and correlated with treatment response (defined as SDAI decrease of ≥ 50% or achieving SDAI remission at follow-up).Results: Fifty-four patients (39 female) were included: 44 with RA (31 seropositive), 8 with psoriatic arthritis, 1 with peripheral spondyloarthritis, and 1 with juvenile idiopathic arthritis. Median baseline SDAI was 17.4 (IQR 12.3–21.4). Treatments comprised TNFi (n=31), JAKi (n=18) and IL-6Ri (n=5). IL-6, sIL6R and sgp130 levels did not differ between SDAI responders and non-responders (all p > 0.05). However, IL-6 levels significantly increased (p < 0.01) after IL6Ri treatment, and sIL6R concentrations were significantly higher than in patients treated with TNFi (p < 0.001) and JAKi (p < 0.05). Conversely, sIL6R significantly decreased with JAKi treatment compared to baseline (p < 0.01).Conclusion: In this pilot study, soluble IL-6 signalling components were not associated with treatment response, but therapy-specific effects were observed: IL6 and sIL6R were increased under IL6R blockade – likely due to feedback and reduced clearance, while sIL6R decreased under JAK inhibition, possibly reflecting lower receptor turnover. These findings suggest class-specific modulation of IL-6 signalling and warrant further investigation.Funding: This study received financial support from the DGRh Forschungsinitiative and the Cluster of Excellence “Precision Medicine in Chronic Inflammation”.Disclosures: JHS: None declared; UG: None declared; HK: None declared; BH: Speakers honorary (Chugai), GJ: None declared; JL: Scientific advisory board/speakers bureau: Abbvie, Amgen, AstraZeneca, BMS, Galapagos/Alfasigma, Janssen-Cilag, Lilly, Novartis, Sanofi, UCB, Research support: Abbott, Boehringer, Gilead, Novartis; SS: Consulting fees: AbbVie, Amgen, Arena, BMS, Biogen, Celltrion, Celgene, Falk, Fresenius Kabi, Galapagos, Gilead, Hikma, IMAB, Janssen, Lilly, MSD, Mylan, Pfizer, Protagonist Provention Bio, Takeda, Theravance and Ventyx, SW: None declared. 0 0 0 0