POS0632 TARGETING NET FORMATION IN EARLY RA PATIENTS; A SPIN-OFF STUDY FROM THE NORD-STAR

Background The formation of neutrophil extracellular traps (NETs) with extrusion nuclear, granular and cytosolic components from a dying neutrophil, has been described extensively in patients rheumatoid arthritis (RA), linked to generation autoantigens (e.g. citrullinated proteins), inflammation organ damage. Thus far there have very few studies describing the effect treatment RA on NET formation, no comparing effects strategies (very) early RA. Objectives To assess different initial treatments Methods NORD-STAR is an international, multicenter, open-label, assessor-blinded, phase 4 study where newly diagnosed started methotrexate (MTX) were randomized 1:1:1:1 a) conventional (either prednisolone tapered 5mg/day, or sulfasalazine combined hydroxychloroquine intra-articular corticosteroids), b) certolizumab pegol, c) abatacept, d) tocilizumab [1] . This spin-off main measuring biomarkers MPO-DNA (Myeloperoxidase-DNA; NETs) calprotectin 24 consecutive Dutch participants 94 Swedish at baseline, 12 weeks after start treatment. Statistical analysis was done using Wilcoxon Signed Rank test for paired samples independent median compare healthy controls SPSS version 28. Results At baseline had elevated levels NETs activation compared as indicated by (median 1080ng/ml vs 133ng/ml, p<0.001) 7185pM 3976pM, p<0.001). Both decreased significantly total group demonstrating reduced activity formation. After treatment, all groups up 93% (Table 1). showed more modest reduction 13%, relatively similar groups, although did not reach statistical significance group. Table 1. are reported (IQR) due skewedness data. Reductions percentage baseline. Measurements marked * if p<0.05, ** p<0.01, *** p<0.001. Baseline Week Reduction Calprotectin (ng/mL ) 1080 (1718) 231 (326) -79% 214 (274) -80% Conventional 1222 (2197) 354 (554) -71% 285 (357) -77% Certolizumab pegol 1166 (1927) 213 (486) -88% 157 (281) -93% Abatacept 850 (1323) 269 (313) -68% 220 (354) -74% Tocilizumab 757 (1346) 169 (195) -54% 184 (168) -53% (pM 7185 (2567) 6503 (2694) -9% 6612 (2542) -8% 7057 (4052) 6396 (2878) -11% 6629 (3092) 7183 (2733) 6492 (3308) -10% 6549 (2608) 7727 (2512) 7562 (4708) -2% 6688 (3882) -13% 6904 (2168) 6120 (1921) 6509 (2113) -6% Figure Median over time (pM) Conclusion These results indicate highly recently patients. All four studied here these detrimental processes within 3 months. seen this line earlier [2] rapid decline markers may contributed minimal radiological progression that trial. References [1]Hetland M et al. BMJ. 2020 [2]Stevens D Ann Rheum Dis. 2022 Acknowledgements: NIL. Disclosure Interests Bas Dijkshoorn: None declared, Ting Wang: Daisy Vedder: Anna Rudin: Dan Nordström Speakers bureau: Novartis, UCB, Consultant of: Abbvie, BMS, Lilly, Pfizer, Roche, Björn Gudbjornsson Amgen Novartis - related work, Kristina Lend: Till Uhlig Grünenthal, Grant/research support from: NORDFORSK, Espen A Haavardsholm AbbVie, Celgene, Janssen, Gilead, Eli-Lilly, Norwegian Regional Health Authorities, South-Eastern Norway Authority, Merete Lund Hetland Biogen, Celltrion, Eli Janssen Biologics B.V, Lundbeck Fonden, MSD, Samsung Biopies, Sandoz, Marte Heiberg: Mikkel Østergaard Galapagos, Merck, Orion, Roche Boehringer-Ingelheim, Hospira, Novo, Regeneron, Sanofi Amgen, Celgene Kim Hørslev-Petersen: Jon Lampa Ronald van Vollenhoven GSK, R-Pharma, AstraZeneca, Miltenyi, Tuulikki Sokka-Isler Medac, Orion Pharma, Bohringer Ingelheim, Christian Lood Redd Gilead Sciences, Boehringer Amytryx, Horizon Bristol Meyers Squibb, Michael Nurmohamed BMS.